Article

Protective effect of Lygodium flexuosum (L.) Sw. extract against carbon tetrachloride-induced acute liver injury in rat

January 2007
Journal of Ethnopharmacology 108(3):320-6

DOI:10.1016/j.jep.2006.05.032

Source
PubMed

Authors:

Research Center

The hepatoprotective potential of Lygodium flexuosum (L.) Sw. was evaluated in male Wistar rats against carbon tetrachloride-induced liver damage in preventive and curative models. Toxic control and n-hexane extract-treated rats received a single dose of CCl4 (150 microL/100g, 1:1 in corn oil). Pre-treated rats were given n-hexane extracts at 200 and 100 mg/kg dose 48, 24 and 2 h prior to CCl4 administration. In post-treatment groups, rats were treated with n-hexane extract at a dose of 200 and 100 mg/kg, 2, 24 and 48 h after CCl4 intoxication. Rats pre-treated with Lygodium flexuosum remarkably prevented the elevation of serum AST, ALT, LDH and liver lipid peroxides in CCl4-treated rats. Rats treated with the extract after the establishment of CCl4 induced liver injury showed significant (p < or = 0.05) protection of liver as evidenced from normal AST, ALT, LDH and MDA levels. Hepatic glutathione levels were significantly (p < or = 0.05) increased by the treatment with the extracts in both the experimental groups. Histopathological changes induced by CCl4 were also significantly (p < or = 0.05) reduced by the extract treatment in preventive and curative groups. Phytochemical studies revealed the presence of saponins, triterpenes, sterols and bitter principles in Lygodium flexuosumn-hexane extract which could be responsible for the possible hepatoprotective action.

Characterization and Evaluation of HGF-Loaded PLGA Nanoparticles in a CCl 4 -Induced Acute Liver Injury Mouse Model

Article

Full-text available

Oct 2019
J NANOMATER

Liver injury can be caused by various harmful factors since the liver is considered the key organ for detoxifying endogenous and exogenous substances. Hepatocyte growth factor (HGF) can regulate redox homeostasis through the expression of antioxidant proteins when the liver is under injury. However, HGF is easily degraded. In this study, we produced three kinds of HGF-loaded poly(lactic-co-glycolic) acid (PLGA) nanoparticles with an initial addition of 2 μ g HGF (NPs-HGF-2 μ g), 4 μ g HGF (NPs-HGF-4 μ g), and drug-free nanoparticles (NPs) using the W/O/W emulsion-solvent evaporation method in accordance with our patent. The morphology and physical characteristics were analyzed, and effects of HGF-loaded PLGA nanoparticles on a CCl 4 -induced acute liver injury mouse model were investigated and compared with HGF solutions. We observed that the morphology and the physical characteristics of the nanoparticles were almost the same, with similar sizes, polydispersity, and zeta potential. HGF-loaded PLGA nanoparticles maintained higher HGF concentrations for a longer period of time in blood and liver tissues. HGF-loaded PLGA nanoparticles increased the SOD activity and GPX levels, decreased the MDA levels in the liver, reduced the necrotic areas of the liver, and decreased the levels of AST, ALT, ALP, T-BIL, BUN, and Scr in blood. In conclusion, our technique for preparing HGF-loaded PLGA nanoparticles was stable and the products were of good quality. HGF-loaded PLGA nanoparticles could provide greater therapeutic benefits on CCl 4 -induced acute liver injury, including antilipid peroxidation and a reduction in indicator enzymes of liver injury.

A comprehensive review on Nepalese wild vegetable food ferns

Article

Full-text available

Nov 2022

Ferns are used as traditional and fascinating foods in many countries. They are also considered to possess important ethnomedicinal values; however, ferns are one of the underutilized plant resources by both scientific and local communities. Pharmagonostical studies reveal that ferns and fern-allies possess several biological activities including antibacterial, antiviral, antifungal, antimalarial, antidiarrheal, anthelmintic, analgesic, anti-inflammatory, antidiabetic, anticancer, neuroprotective, nephroprotective, hepatoprotective, antifertility, etc. Flavonoids and terpenoids are major secondary metabolites present in ferns. Ugonins, particularly isolated from Helminthostachys zeylanica, have found diverse bioactivities. Ptaquiloside, a norsesquiterpene glucoside, found in Pteridium revolutum, Dryopteris cochleata and Polystichum squarrosum, is one of the hazardous metabolites of ferns which is responsible for the toxic effect. Alkaloids are reported to be present in the ferns; however, the qualitative data are uncertain. Some fern metabolites, such as cyanogenic glycosides and terpenoids, are considered to possess defensive activity against animal attacks. Some ferns are also used for manuring as biological alternative to pesticides. Nepalese have consumed at least 33 species of ferns and fern-allies belonging to 13 families, 20 genera as cooked vegetable foods. The aim of this review is compilation of information available on their distribution, ethnomecinal values, pharmcognosy, pharmacology and phytochemistry.

A Comprehensive Review on Nepalese Wild Vegetable Food Ferns

Article

Full-text available

Jan 2022

Phytochemical Constituents of Carrot (Daucus carota) Fruit Juice and its Hepatoprotective Property in CCl 4 -Induced Liver Cirrhotic Rats

Article

Full-text available

Aug 2021

Aim: This study evaluated the phytochemical constituents of Carrot fruit juice (CFJ) and its hepatoprotective property in CCl4-induced liver cirrhotic rats. Study Design: Sixty male rats of weight ranging from 150-180 g were completely randomized into six groups. All rats were administered 0.5 ml/kg CCl4 subcutaneously thrice weekly except groups 1, 2, 3, and 4 while rats in groups 3 and 6 and groups 4 and 5 orally received 2.5 and 5.0 ml/kg of CFJ on daily basis for 12 weeks. Results: The preliminary qualitative phytochemical screening of extract revealed the presence of alkaloids, flavonoids, cardiac glycosides, carbohydrate, saponin, phenolic compound and tannins. The extract treated groups significantly revealed an increase in liver cirrhotic emaciated body weight and reduction in the liver index, a reversal of liver marker enzymes activities, an increase in enzymic and non-enzymic antioxidants with a decrease in malondialdehyde level reduction in C-reactive protein, interleukin-6, alpha-fetoprotein, and carcinoembryonic antigen. Exposure of animal to CCl4 induces oxidative stress, increases the generation of reactive oxygen species and myeloperoxidase activity, and reduces cell viability but was reversed by the CFJ. Conclusion: The result showed that CFJ is a promising therapeutic option for treating liver failure.

Cell-free DNA as a potential marker to predict carbon tetrachloride-induced acute liver injury in rats

Article

Full-text available

Jun 2012

Finding an optimal biomarker for the noninvasive evaluation of acute liver injury (ALI) may be of great value in predicting clinical outcomes and investigating potential treatments. We investigated cell-free DNA (CFD) as a potential biomarker to predict carbon tetrachloride-induced ALI in rats. Forty-five Sprague-Dawley rats were randomly assigned to three groups. ALI was induced by carbon tetrachloride via a nasogastric tube at 1, 2.5, or 5 ml/kg of a 50 % solution. Fifteen additional rats underwent a sham procedure. Blood samples were drawn at time t which was 0 (baseline), 3, 6, 12, 24, 48, 72, 96, and 120 h for the measurements of CFD, glutamate-pyruvate transaminase (GPT), glutamate-oxaloacetate transaminase (GOT), and total bilirubin. Prothrombin time and histology were examined at 24 and 120 h following injection of 5 ml/kg carbon tetrachloride in 18 additional rats and in 10 control rats. CFD levels in rats subjected to carbon tetrachloride-induced ALI were significantly increased in all blood samples starting at 12 h after the induction of ALI (p < 0.001), reaching peak levels at 24 h. Blood GOT, GPT, and total bilirubin were elevated in all blood samples starting at 3 h after the induction of ALI (p < 0.0001), reaching peak levels by 48 h. A positive correlation was demonstrated between CFD levels and GOT (R (2) = 0.92), GPT (R (2) = 0.92), and total bilirubin (R (2) = 0.76). CFD levels correlated with liver damage seen on histological examination, as well as predicted liver damage, at 24 h after ALI. CFD may be a useful biomarker for the prediction and measurement of ALI. There is no evidence to suggest that CFD is superior to other available noninvasive biomarkers.

The effects of gallic acid on inflammation and oxidative stress in valproic acid-induced hepatotoxicity in rats

Article

Full-text available

Feb 2023
Comp Clin Pathol

Valproic acid (VPA) is one of the most broadly used drugs for epilepsy disorders worldwide. Despite its great effectiveness, this drug causes liver toxicity. In this work, the effects of gallic acid (GA) on hepatic injury caused by VPA were investigated. We randomly divided 48 Wistar rats into 6 groups. Group 1 was considered as control. The second group received only valproic acid. The third group was a positive control group which was administrated with VPA and then Silymarin. The fourth, fifth, and sixth groups also received GA after taking valproic acid. Then serum lipid profile, alkaline phosphatase (ALP), aspartate transaminase (AST), alanine aminotransferase (ALT), inflammatory factor interleukin-1beta (IL-1β), and liver biomarkers of oxidative stress were assessed. VPA caused a substantial increase (p < 0.05) in AST, ALP, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), ALT, triglyceride (TG), blood urea nitrogen (BUN), very low-density lipoprotein cholesterol (VLDL-C), creatinine (Cr), urea, protein carbonyl (PC), and malondialdehyde (MDA) levels plus serum inflammatory factor IL-1β. This drug also caused an obvious decrease (p < 0.05) in high-density lipoprotein cholesterol (HDL-C), catalase (CAT), ferric-reducing antioxidant power (FRAP), vitamin (Vit) C, and superoxide dismutase (SOD). Exposure to GA not only leads to a considerable improvement (p < 0.05) against hepatic damage caused by valproic acid, but also increases the antioxidant system and reduces serum ALP, TC, AST, TG, ALT, BUN, LDL-C, Cr, VLDL-C, urea, PC, and MDA levels. GA with its antioxidant properties shows a protective effect against hepatotoxicity caused by valproic acid. This antioxidant reduces the toxicity induced by the VPA by reducing oxidative stress and inflammatory effects of IL-1β.

Plants-based medicine implication in the evolution of chronic liver diseases

Article

Full-text available

Jan 2023
BIOMED PHARMACOTHER

Hepatic disorders are considered major health problems, due to their high incidence, increased risk of chronicling or death and the costs involved in therapies. A large number of patients with chronic liver diseases use herbal medicines and dietary supplements in parallel with allopathic treatment.The current review provides a thorough analysis of the studies conducted on the most important species of medicinal plants used in this disease, bioactive compounds and on the activity of herbal medicines in the evolution of chronic liver diseases. However, a negative aspect is that there is frequently a lack of comprehensive data on the progression of the illness and the living standards of patients who are affected when evaluating the effects of these phytocomponents on the evolution of chronic liver disease, the patients' health, and their quality of life. It is essential to take this impairment into account when evaluating the long-term effects of herbal treatments on the health of individuals who suffer from liver illness. Bioactive phytocomponents may be a suitable source for the development of novel medications due to the correlation between traditional uses and medical advances. Additional high-quality preclinical examinations utilizing cutting-edge approaches are needed to assess safety and effectiveness and to detect, categorize, and standardize the active substances and their formulations for the most suitable therapeutic management of liver illnesses.

Particle Size Effects on Antioxydant and Hepatoprotective Potential of Essential Oil from Eucalyptus camaldulensis Leaves against Carbon Tetrachloride-Induced Hepatotoxicity in Rats

Article

Full-text available

Jan 2022

Hepatoprotective activity of the ethanolic extract of Morus indica roots from Indian Bodo tribes

Article

Full-text available

Jan 2022

The roots of Morus species are well described in the Pharmacopoeia of the People's Republic of China (ChP) for its traditional use in treating liver fibrosis due to its hepatoprotective property. However, little is known about the hepatoprotective effect of the roots of Morus indica L. (RoMi), and the pharmacological mechanism(s) are uncertain due to its intricacy. Therefore, this study evaluates the hepatoprotective activity of the ethanolic extract of RoMi (eRoMi) against the CCl4-induced in-vivo animal model at different dosages (100 and 200 mg/kg BW) in comparison with silymarin as a positive control. The hepatoprotective activity of eRoMi was evaluated by measuring the levels of serum biomarkers, hepatic antioxidant enzymes and was verified by histological studies. Interestingly, 1,2-bis(trimethylsilyl) benzene, 1,4-phenylenebis (trimethylsilane), 2,4,6-cycloheptatriene-1-one, 3,5-bis-trimethylsilyl and α-amyrin were the active components found in eRoMi as detected by GC–MS. Oral administration of eRoMi (200 mg/kg BW) to rats significantly protected serum biochemical parameters (increased ALT, AST, LDH, bilirubin and GGT as well as depletion of antioxidant enzymes and hepatic GSH) and elevation in hepatic lipid peroxidation as compared to CCl4-treated rats. The hematological indices such as erythrocytes, hemoglobin, monocytes and lymphocytes were also normal in eRoMi-treated rats. The histopathological evaluation indicated a significant restoration of liver structure as compared to silymarin. This study is the first scientific validation for the traditional use of eRoMi to understand its hepatoprotective activity.

Protective Effects of Cydonia oblonga Mill. Fruit on Carbon Tetrachloride-induced Hepatotoxicity Mediated through Mitochondria and Restoration of Cellular Energy Content

Article

Full-text available

Oct 2020

Quince (Cydonia oblonga Mill.) is one of the medicinal plant with a broad range of pharmacological activities such as hepatoprotective effect. The present study was conducted to evaluate the effect of aqueous extract of Cydonia oblonga Mill. fruit (ACOF) against carbon tetrachloride (CCl4)-induced liver damage in rats. Hepatotoxicity was induced by CCl4 and all tested group animals were treated with the plant extract at a dose of 75, 150, and 300 mg/kg orally for 5 days. Blood was collected for the assessment of serum marker enzymes (alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH)). Adenosine triphosphate (ATP) of liver mitochondria was also measured using a validated high performance liquid chromatography (HPLC) method. The antioxidant capacity of the extract resulted in the reduction of MDA and the restoration of GSH in the liver (P < 0.05). Free radical scavenging activity of the extract was evaluated by DPPH method and the IC50 value was found to be 568 μg/mL. Our results indicated that bioenergetic depletion occurred in the intoxicated rats as a consequence of mitochondrial dysfunction and ATP production collapse. ACOF markedly restored ATP contents that is a key step in liver regeneration. It can be concluded that the role of ACOF to improve liver function on CCl4-hepatoxicity could be attributed, at least partially, to its action at mitochondira by preventing the loss of ATP content.

Evaluation of Hepatoprotective and Antioxidant Activity of Ethanolic Extract of Artabotrys zeylanicus Stem against Various Hepatotoxins Induced Hepatotoxicity in Albino Wister Rats

Article

Feb 2021

The objective of the present study was to investigate the antioxidant and hepatoprotective activity of ethanolic stem extract of Artabotrys zeylanicus against paracetamol (PCT), Ethanol (ETN) and Isoniazid and Rifampicin (IR) induced hepatotoxicity in Albino wister rats. Methodology: The material was dried in shade, they were powdered and extracted with ethanol. Preliminary Phytochemical tests were done. The hepatoprotective activity of the ethanol extract was assessed in Albino wister rats. PCT (3 g/kg), ETN (5 gm/kg) and IR (100 mg/kg) has enhanced the levels of various biochemical markers of hepatic damage like Serum Glutamic Oxaloacetic Trasaminase (SGOT), Serum Glutamic pyruvic transaminase (SGPT), Alkaline phosphatise (ALP), bilirubin. Antioxidant levels were tested in all the Hepatotoxins treated and untreated groups. Results: The various biochemical and Histopathological investigations done were Serum Glutamic Oxaloacetic Trasaminase (SGOT), Serum Glutamic pyruvic transaminase (SGPT), Alkaline phosphatise (ALP), Bilirubin, antioxidant activity by 1,1-diphenyl 2-picryl hydrazyl (DPPH), Nitro Blue Tetrazolium (NBT), Hyderogen peroxide (H2O2), lipid perioxidation, hyderoxil radical and nitric oxide. Treatment of ethanolic extract of stem of A. zeylanicus (100mg/kg, 200mg/kg and 400mg/kg body weight) has brought back the altered levels of biochemical markers to the near normal levels in the dose dependent manner. Ethanolic extract of A. zeylanicus were observed to inhibit oxidant stress with the maximum value of 71% and 62% at the concentration of 100 µg/mL. The crude ethanolic extract of A. zeylanicus had a calculated IC50 value of 62.2 and 63.25 μg/mL, which is nearly similar to the calculated IC50 value of the known antioxidant, ascorbic acid, ie 65.3 μg/mL. While the rats treated with AZ extract (100, 200 and 400 mg/kg) which were shown as reduction/absence of inflammatory cells, vascular congestion, cellular degeneration, necrosis and vacuoles. In contrast, the lower doses (100 mg/kg) of ethanolic extract of AZ stem shown low protection than at higher dose 400 mg/kg. Conclusion: Our findings suggested that A. zeylanicus ethanol stem extract possessed a potent antioxidant and hepatoprotective activity.

In vivo Hepatoprotective and in vitro Radical Scavenging Activities of Extracts of Rumex abyssinicus Jacq. Rhizome

Article

Full-text available

Aug 2020

Background Liver diseases contribute a prominent global burden of mortality and morbidity. The current therapies of liver diseases have numerous limitations including severe adverse effects. This denotes that new more effective, safer, and cheaper drugs are required and medicinal plants used in traditional medicines often offer ideal opportunities. Accordingly, the present study aimed to evaluate the in vivo hepatoprotective and in vitro radical scavenging activities of dried rhizome extracts of Rumex abyssinicus (R. abyssinicus), which is traditionally claimed to provide hepatoprotection. Materials and Methods Hepatoprotective activity of extracts was evaluated using carbon tetrachloride (CCl4)-induced liver injury in mice. Pre- and post-treatment models were employed to test the effect of the extracts and silymarin (standard drug). Serum biochemical markers and liver histopathology were used as parameters to evaluate hepatoprotective activities whereas in vitro radical scavenging activity was tested by 2, 2-diphenyl-2-picrylhydrazyl hydrate (DPPH) assay. Results and Conclusion Oral administration of CCl4 (1 ml/kg) significantly (P<0.001) raised the serum levels of liver enzyme markers compared to the normal control group. Pre-treatment with 125, 250, and 500 mg/kg of R. abyssinicus extract reduced the serum level of CCl4-induced rise in liver enzyme markers with the highest reduction observed at a dose of 500 mg/kg. Likewise, in the post-treatment model, the crude extract and butanol fraction at dose 500 mg/kg reduced levels of liver enzymes. Histopathological examinations revealed lesser liver damage of extract-treated mice compared to the toxic (CCl4-treated) controls. The in vitro radical scavenging activity of the different extracts showed concentration-dependent radical scavenging activity. Thus, the results of this study may justify the traditional use of the plant as a hepatoprotective agent. Conclusion Results of serum biochemical markers and histopathological examinations of CCl4-induced mice models, in the present study, show the hepatoprotective potential of extracts from the rhizome of R. abyssinicus.

ANTIMICROBIAL ACTIVITIES AND PHYTOCHEMICAL INVESTIGATION OF FERN, LYGODIUM FLEXUOSUM (LINN) SW.

Article

Jun 2017

Jeeshna M V

The present study revealed the presence of many medicinally active constituent in Lygodium flexuosum, suggesting that this species have potential to synthesize useful secondary metabolites. In this studies two different types (vegetative material and sporophyll bearing type) of this species showed the presence of secondary metabolites such as alkaloids, flavonoids, saponins, tannins, phenols and glycosides. In which vegetative material showed the presence of all secondary metabolites. The low polar solvent extracts such as petroleum ether and acetone showed minimum presence of secondary metabolites. The antibacterial studies revealed that methanol extracts of sporophyll type exhibited significant activity (8.5 mm) against the bacterium, Klebsiella pneumonia. The next antibacterial activity showed by chloroform extracts of sporophyll type against the same bacteria (8.2 mm). In antifungal studies, methanol extracts of vegetative material has the highest inhibitory activity (19.3 mm) against the fungus Cladosporium sp. Next higher fungal activity was showed by same extract of sporophyll type against the fungus Rhizopus sp. (16.08 mm). The study confirms the antimicrobial potential of Lygodium flexuosum extracted using various solvents.

Nutraceutical and Bioactive Significance of Ferns with Emphasis on the Medicinal Fern Diplazium

Chapter

Jul 2019

Being primitive vascular plants, pteridophytes (ferns) have wide geographic distribution in different climatic regimes by bridging the gap between lower and higher plants. Compared to the angiosperms, nutraceutical and bioactive potential of ferns attracted less attention. Many ferns are nutraceutically viable owing to their rich source of protein, fiber, minerals, vitamins, essential amino acids, and fatty acids. Besides bioherbicide potential, ferns are endowed with chemopreventive, hepatoprotective, cytotoxic, antihyperglycemic, leishmanicidal, trypanocidal, antimicrobial, antinociceptive, and immunomodulatory metabolites. Ferns are also valuable source of low-cost proteins, starch, and components of cosmeceutical significance. The genus Diplazium has pantropical distribution consisting of versatile nutraceutical and bioactive compounds. Future research should intensify toward exploitation of ferns as nutraceutical, healthcare, and industrial products to open up new avenues for food and pharmaceutical industries. Bioactive compounds · Ethnic food · Leafy vegetable · Nutraceutical potential · Pteridophyte · Riparian fern

In vivo hepatoprotective and In vitro radical scavenging activities of Cucumis ficifolius A. rich root extract

Article

Jun 2019
J ETHNOPHARMACOL

Galangin-loaded, liver targeting liposomes: Optimization and hepatoprotective efficacy

Article

May 2018
J DRUG DELIV SCI TEC

The aim of this study was to develop liver targeting galangin-loaded liposomes (Galangin-Liposomes) and evaluate their oral bioavailability. Box Behnken design was applied to optimize the formulation of Galangin-Liposomes by assessing encapsulation efficiency. The optimized Galangin-Liposomes were characterized by zeta potential, encapsulation efficiency, morphology, stability and in vitro release. Meanwhile, in vivo pharmacokinetics and tissue distributions were studied. Morphology of the selected Galangin-Liposomes revealed spherical and uniformly distributed nanoparticles with size of 74.67 ± 7.09 nm and encapsulation efficiency of 92.36 ± 2.71%. The formulation also significantly increased the extent of galangin release in vitro as well as its oral bioavailability (470.12%) in vivo. Furthermore, the tissue distribution studies further showed that the Galangin-Liposomes were enriched in the liver and exhibited better hepatoprotective effects in CCl4-intoxicated mice compared with the free galangin (p < 0.01). Collectively, these results indicated that the liposomes could serve as an effective delivery system to achieve improved oral bioavailability and liver targeting of galangin.

An Insight of Herbal Drugs and their Pharmaceutical Formulations Reported to have Hepatoprotective Activity

Article

Full-text available

Apr 2018

Background: Medicinal plants play an important role in the world’s human healthcare system including folk practices as well as Ayurveda, Unani and Siddha. Approximately, 80% of the world’s human population relies on the usage of traditional medicine which is primarily based on plant-derived drugs. Liver is the most important organ for the detoxification of various toxins and disposition of the endogenous substances. It is always exposed to the toxins and chemotherapeutic agents that lead to hepatotoxicity. Herbal drugs and their pharmaceutical formulations have been used in the treatment of liver diseases and hepatotoxicity for a long time. Aims: The present review is aimed at compiling data on promising medicinal plants that have been tested in hepatotoxicity models using the modern scientific system. Materials and Methods: Literature surveys on scientific national and international journals, books as well as electronic resources were performed. Results: It showed several herbal drugs and their pharmaceutical formulations that have hepatoprotective activity. The herbal medicines mentioned were of an enormous value. Conclusion: This reported insight of herbal drugs and their pharmaceutical formulations will definitely be helpful to the future researchers and the practitioners while deciding and choosing an effective drug for the treatment of liver diseases and hepatotoxicity.

Effect of Punica Granatum (Pomegranate) on serum ALT and AST in Carbon tetrachloride induced liver damage in Wistar Albino Rats

Article

Full-text available

Sep 2016

p> Background: Liver diseases are associated with significant morbidity and mortality. Punica granatum may have free radical scavenging activity and it can be used for the prevention and treatment of liver damage. Objective: To observe the hepatoprotective effects of Punica granatum on CCl₄ induced liver damage in rats. Methods : The experimental study was carried out in the Dept of Physiology, Dhaka Medical Ccollege, Dhaka from July 2013 to June 2014. For this purpose, 36 wistar albino rats were studied. After acclimatization for 7 days, they were divided into two groups-control and experimental group. Control group were subdivided into BC (Baseline control), CC (CCl₄ treated control) and SC (Silymarin treated control). Experimental group were subdivided into CP-APT (CCl₄ pretreated and aqueous extract of pomegranate treated), CP-EPT (CCl₄ pretreated and ethanolic extract of pomegranate treated) and APP-CT (Aqueous extract of pomegranate pretreated and CCl₄ treated). Each sub group consisted of 6 rats. All rats received basal diet for 8 days. In addition to basal diet on 8^th day, BC received single dose olive oil and CC received CCl₄. Rats of SC received silymarin for 8consecutive days. In experimental groups, CP-APT received aqueous extract of Pomegranate and CP-EPT received ethanolic extract of Pomegranate for 8consecutive days. Moreover, APP-CT received aqueous extract of Pomegranate for 8 consecutive days and CCl₄ only on 8^th day. All rats were sacrificed on 9^th day and then blood samples were collected. Serum ALT and AST levels were estimated by using standard laboratory kits. Statistical analysis was done one way ANOVA and Bonferroni test. Results: The mean serum AST and ALT levels were significantly (p<0.001) higher in CC in comparison to those of BC. Serum AST and ALT levels of all experimental groups were significantly (P<0.001) lower than CC. Silymarin used as a standard reference also exhibited significant hepatoprotective activity against CCl₄ induced hepatotoxicity Conclusion: From the result of present study it can be concluded that, Pomegranate may have hepatoprotective effect by lowering ALT and AST levels Bangladesh Soc Physiol. 2016, June; 11(1): 23-28</p

Antioxidant and proapoptotic effects of anthocyanins from bilberry extract in rats exposed to hepatotoxic effects of carbon tetrachloride

Article

Jun 2016

Aims: The aim of this research was to determine the hepatoprotective effects of anthocyanins from bilberry extract in rats exposed to carbon tetrachloride (CCl4) by monitoring the parameters of oxidative stress and apoptosis, and by performing the histopathological and morphometric analyses. Main methods: Animals were divided into four groups: Group I (0.9% NaCl-10days), Group II (bilberry extract, 75mg/kg-10days), Group III (0,9% NaCl-9days, and on the tenth day CCl4-2ml/kg), Group IV (bilberry extract, 75mg/kg-10days and on the tenth day CCl4-2ml/kg). Key findings: Bilberry extract led to a significant decrease in the activity of biochemical parameters in serum (AST, GGT, LDH, and ALT), the activity of pro-oxidative enzyme xanthine oxidase, as well as the level of lipid peroxidation in the liver in Group IV compared to Group III (p<0.01). Bilberry extract resulted in a significant increase in the activity of the antioxidant markers-catalase (p<0.05), superoxide dismutase, glutathione S-transferase and glutathione peroxidase (p<0.01), and the concentration of reduced glutathione (p<0.05) in Group IV in relation to Group III. The application of bilberry extract resulted in an increase in the number of apoptotic hepatocytes and the activity of caspase-3 in the liver tissue (p<0.01). The reduction of coagulation necrotic areas was proved (p<0.001) as well as the number of macrovesicular hepatocytes (p<0.01), along with an increased mitotic activity (p<0.01) in Group IV compared to Group III. Significance: Anthocyanins from bilberry extract have strong antioxidant properties and therefore can be considered as powerful hepatoprotectives in natural products.

The essential oil of Artemisia capillaris protects against CCl4-induced liver injury in vivo

Article

Full-text available

Jan 2016
REV BRAS FARMACOGN

To study the hepatoprotective effect of the essential oil of Artemisia capillaris Thunb., Asteraceae, on CCl4-induced liver injury in mice, the levels of serum aspartate aminotransferase and alanine aminotransferase, hepatic levels of reduced glutathione, activity of glutathione peroxidase, and the activities of superoxide dismutase and malondialdehyde were assayed. Administration of the essential oil of A. capillaris at 100 and 50 mg/kg to mice prior to CCl4 injection was shown to confer stronger in vivo protective effects and could observably antagonize the CCl4-induced increase in the serum alanine aminotransferase and aspartate aminotransferase activities and malondialdehyde levels as well as prevent CCl4-induced decrease in the antioxidant superoxide dismutase activity, glutathione level and glutathione peroxidase activity (p < 0.01). The oil mainly contained β-citronellol, 1,8-cineole, camphor, linalool, α-pinene, β-pinene, thymol and myrcene. This finding demonstrates that the essential oil of A. capillaris can protect hepatic function against CCl4-induced liver injury in mice.

Effect of Aqueous Leaf Extract of Borreria verticillata Species of Sudano-Sahelian Savanna on CCl 4 Induced Hepatotoxicity

Article

Full-text available

Jan 2015

Preliminary phytochemical screening of Borreria verticillata species of Sudano-Sahelian savanna and the effect of aqueous leaf extract of the plant were studied in CCL 4-induced hepatotoxicity rats. Screening of the aqueous extract indicates the presence of alkaloids, flavonoids, tannins, glycosides, sterol and saponins. While athraquinone was absent. Serum levels of aspartate aminotransferase (AST), alanine amino transferase (ALT), alkaline phosphatase (ALP), total protein (TP) and bilirubin (BL) were analysed in rats intraperitoneally administered with 100 mg/kg CCl 4 followed by oral treatment with 300mg/kg of aqueous leaf extract of B. verticillata for 48 and 96hrs. The rats treated for 48 hours after had serum AST, ALT, ALP, TP and BL levels not statistically different (P>0.05) compared to both normal control and positive control (treated with 100mg/kg standard drug) although the value of positive control was slightly lower than the test values. However, the test values were statistically lower compared to toxicity control at P< 0.05. The serum AST, ALT, ALP, TP and BL levels when the treatment was extended to 96 hours showed similar pattern to 48 hours treatment. Even though the test values with respect to the enzymes activity were slightly lower in the extended treatment. This result indicates the hepatocurative properties of aqueous leaf extract of B. verticillata on CCL 4-induced hepatotoxicity rats, which could be attributed to its phytochemical contents.

Antioxidant and hepatoprotective effect of aqueous and ethanolic extracts of important medicinal plant Pongamia pinnata (Family: Leguminoseae)

Article

Oct 2015

Objectives: A lot of herbal plants and polyherbal formulations are used for the treatment of liver diseases. Methods: This present investigation was aimed to assess the hepatoprotective activity of aqueous and ethanol extract of Pongamia pinnata leaves against acetaminophen-induced liver damage in albino rats. Silymarin as a standard drug for comparing the activity. The activity was assessed by comparing the biochemical parameters in serum levels such as serum glutamate pyruvate transaminase, serum glutamate oxalate transaminase, total bilirubin, alkaline phosphatase of plant extracts treated group with acetaminophen treated animals. Results: Results showed, ethanolic extract treated group showed highly significant activity (p<0.001), whereas aqueous extract treated group has shown the significant (p<0.01) action but less compared with ethanolic extract. Plant extracts restores biochemical enzymes and brings down to normal as compared to standard drug silymarin. Conclusion: This results shows and confirms the significant protective activity against acetaminophen-induced hepatotoxicity.

Uvaria afzelii root extract protects the liver against damage caused by carbontetrachloride ingestion

Article

Apr 2015

Introduction: Hepatoprotective activity of crude aqueous extract of Uvaria afzelii (UV) root was investigated and compared with a standard hepatoprotective drug (silymarin) in Wistar rats. Materials and Methods: Twenty-five adult Wistar rats were randomly assigned into a control Group (A) and four treatment Groups (B-E) each containing five rats ( n = 5/group). Animals in each group were allowed access to 200 g/day growers' mash and water ad libitum. Rats in the treatment groups were administered with intraperitoneal injection of 1 ml/kg body weight of 30% carbon tetrachloride (CCL 4 )/olive oil mixture every 72 h interval during the 15 days experimental period. Rats in Group B were not pretreated while Groups C, D and E rats were pretreated daily with 50 mg/kg body weight of silymarin, 250 mg/kg and 500 mg/kg body weight of crude aqueous extract of UV root respectively. On the 15th day of the experiment, the rats were sacrificed and blood samples were collected to assay for serum liver enzymes; aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) as well as total protein (TP).The liver tissues were also excised and fixed in 10% buffered formal saline for routine histological examination. Result: The result obtained showed that UV root extract significantly ( P P 4 /olive oil and not significant ( P 4 /olive oil only showed vacuolation (presence of fat droplets), portal vein congestion, and moderate tissue separation. These observations were reduced in the liver of rats pretreated with UV root extract and silymarin. Conclusion: These findings indicate that root extract of UV possess hepatoprotective activity against Ingested hepatotoxic insults.

Naringin prevents carbon tetrachloride-induced acute liver injury in mice

Article

Full-text available

Jan 2015

The protective effects and mechanisms of action of naringin (Nar) against carbon tetrachloride (CCl4)-induced hepatic injury in mice were investigated. The results showed that oral administration of Nar significantly decreased the levels of alanine transaminase and alanine transaminase in serum, nitric oxide, inducible nitric oxide synthase and thiobarbituric acid reactive substances in hepatic tissue, and markedly increased the levels of superoxide dismutase, catalase, glutathione peroxidase and glutathione/oxidized glutathione ratio compared with the model group. Transmission electron microscopy and histopathology assay also showed the hepatoprotective effect of Nar against the damage. In addition, Nar markedly decreased cytochrome P4502E1 expression, suppressed oxidative stress, inflammation and apoptosis, and decreased phosphorylation levels of mitogen-activated protein kinases caused by CCl4. These results imply that Nar has perfect effect against CCl4-induced liver injury in mice, which should be developed as an effective food and healthcare product for the treatment of liver injury in the future.

Hepatoprotective effects of Portulaca oleracea extract against CCl 4 -induced damage in rats

Article

Dec 2014
PHARM BIOL

Context: Purslane (Portulaca oleracea L., Portulacaceae) has been traditionally used in folk medicine to afford protection against liver injury, although its actual efficacy remains uncertain. Objective: To evaluate purslane as a hepatoprotective agent, we investigated the protective effect of its ethanol extract against carbon tetrachloride (CCl4)-induced hepatic toxicity in rats. Materials and methods: A total of 108 male Wistar rats were randomly divided into 12 groups. The first group was maintained as normal control, whereas CCl4 (0.5 ml/kg bw, 50% CCl4 in olive oil, i.p.), purslane extract (0.005, 0.01, 0.05, 0.1, and 0.15 g/kg bw, intragastrically), and purslane extract (five doses as above) along with CCl4 were administered to the Groups II, III-VII, and VIII-XII, respectively. The rats were sacrificed on the 30th day, and blood was withdrawn by cardiac puncture. Liver damage was assessed by measuring hepatic marker enzymes (ALT, AST, ALP, GGT, and SOD) and histopathological observation. Results: Treatment with CCl4 resulted in increased serum activities of marker enzymes with a concomitant decrease in SOD. Histological alterations were also observed in the liver tissue upon CCl4 treatment. Administration of purslane extract (0.01, 0.05, 0.1, and 0.15 g/kg b.w.) significantly showed a marked tendency towards normalization of all measured biochemical parameters in CCl4-treated rats. Histopathological changes also paralleled the detected alteration in markers of liver function. Discussion and conclusion: These results demonstrate that purslane exerts protective effects against CCl4-induced damage in rat liver and supports a potential therapeutic use of purslane as an alternative for patients with liver diseases.

Hepatoprotective activity of ginsenosides from Panax ginseng adventitious roots against carbon tetrachloride treated hepatic injury in rats

Article

Oct 2014
J ETHNOPHARMACOL

Hepatoprotective effect of Brassica oleracea vegetable and its leaves in Paracetamol induced liver damage in albino rats

Article

Sep 2014

The liver is the key organ involved with almost all the biochemical pathways related to energy production, growth and fight against disease, nutrient supply, and reproduction. Drug-induced toxicity has turn out to be a major trouble worldwide. Paracetamol is a commonly used drug and continues use may cause liver damage. In this present investigation the commonly using vegetable cabbage (Brassica oleracea) and its leaf is used for the hepatoprotective action against paracetamal induced liver damage. The animals are divided into seven groups, in that four groups are treated with cabbage and its leaf. The parameters like AST, ALT, gamma GT, bilirubin, total protein and antioxidant levels of Superoxide Dismutase (SOD), catalase, Glutathione Peroxidase levels in normal range due to the treatment with cabbage and its leaf extracts. The histological change shows the good hepatoprotective action of cabbage and its leaf extracts.

Magnesium attenuates carbon tetrachloride-induced hepatic injury in rats

Article

Full-text available

Feb 2014
MAGNESIUM RES

In the present study, we investigated the protective effects of magnesium sulfate (MgSO4) against carbon tetrachloride (CCl4)-induced liver damage in rats. MgSO4 (0.001, 0.01, 0.05 and 0.1 Mg(2+) g/kg b.wt.) was administered intragastrically for 28 consecutive days to male, CCl4-treated rats. The hepatoprotective activity was assessed using various biochemical parameters such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyltransferase (GGT) and superoxide dismutase (SOD) activity. Histopathological changes in the liver, of different groups were also studied. Administration of CCl4 increased serum ALT, AST, ALP and GGT, but decreased liver SOD activities in rats. Treatment with MgSO4 significantly attenuated these changes to nearly normal levels. The animals treated with MgSO4 showed decreased necrotic zones and reduced hepatocellular degeneration when compared to liver exposed to CCl4 alone. Hepatic damage was reduced in MgSO4-treated rats. Thus, our results suggest that MgSO4 has potential for the treatment of liver damage resulting from chemical intoxication.

Local Knowledge on Wild Edible and Economically Important Pteridophytes of India: A Review

Article

Full-text available

Oct 2023
HUM ECOL

Wild edible plants provide a wide range of dietary benefits in the form of bioactives, minerals, and fibers. Pteridophytes (ferns and lycophytes) are an important source of edible plants and play a significant role among rural communities in India and elsewhere. Despite many phytochemical and biological studies of pteridophytes, much less attention has been paid to traditional knowledge of their dietary, medicinal, and other uses. We address this gap with an overview of traditional uses of wild edible and economically important pteridophytic species in India, their pharmacological importance, and major phytochemicals. A total of 142 species belonging to 26 families and 66 genera were noted as edible and economically important species. The data show a strong relationship between indigenous communities and wild pteridophytic species as a potential source of their livelihood. This local ecological knowledge on pteridophytes can be preserved and utilized to combat dietary deficiencies, improve the livelihoods of rural communities, and could guide future research programs to encourage socioeconomic development in rural areas and biodiversity conservation. This is the first report to broadly review the edible and economic uses of pteridophytes in India.

Biopotency of Pteridophytes: A Review

Chapter

May 2022

From Silurian period, pteridophytes exist in the nature and expected to harbour various useful secondary metabolites. By the presence of secondary metabolites, pteridophytes are able to survive for more than 450 million years and house various biological activities, viz. anti-bacterial, anti-cancer, anti-diabetic, anti-fungal, anti-inflammatory, anti-oxidant, hepatoprotectivity, wound healing, etc. The review intends to summarize the available biopotential of pteridophytes from 2000 to 2021. A total of 244 species are taken into account for the present review. This chapter recorded anti-oxidant potential (135), anti-bacterial and anti-fungal activities (97), cytotoxic properties (61), anti-cancer activities (39), anti-inflammatory activities (26), anti-diabetic potential (23), hepatoprotective properties (9), wound healing potential (7) and larvicidal activities (6) of pteridophytes. We made an attempt to provide an update on the biopotential of pteridophytes. This review might be useful for the pteridologist, phytochemist and pharmacist for further research.

J A S E M . OURNAL OF PPLIED CIENCE AND NVIRONMENTAL ANAGEMENT Liver function status in Streptozotocin Induced Diabetic Rats Treated with Extracts of some Anti-diabetic Medicinal plants

Article

Apr 2022

Medicinal plants with hepatoprotective potentials against carbon tetrachloride-induced toxicity: a review

Article

Full-text available

Dec 2021

Background Carbon tetrachloride (CCl 4 ) is a well-characterized hepatotoxic agent. With rising cases of liver diseases, the identification, assessment, and development of hepatoprotective agents from plants source has become imperative. Main body With arrays of literature on plants with hepatoprotective potentials, this review sourced published literatures between 1998 and 2020 and systematically highlighted about 92 medicinal plants that have been reported to protect against CCl 4 -induced liver injury in animal models. The results show that herbal plants provide protection for the liver against CCl 4 by downregulation of the liver marker enzymes and activation of antioxidant capacity of the liver cells with the restoration of liver architecture. We also provided the traditional and accompanying pharmacological uses of the plants. A variety of phytochemicals mostly flavonoids and polyphenols compounds were suggested to offer protection against liver injuries. Conclusion It can be concluded that there are a variety of phytochemicals in plant products with hepatoprotective activity against CCl 4 -induced toxicity in animal models.

International Journal of Veterinary Science and Research Clinical safety of amino acids and vitamins administered through parenteral route

Article

Full-text available

Aug 2017

CC By 055 Citation: de Moraes AC, Scherma MR, da Rosa Prado EJ, de Faria VP, da Silva IC, et al. (2017) Clinical safety of amino acids and vitamins administered through parenteral route. Int J Vet Sci Res 3(2): 055-061. DOI: http://dx. Abstract The parenteral use of amino acids and vitamins has been used to improve performance in animal production. However, few studies demonstrating the toxicity of these compounds. The present investigation evaluated the toxicological and clinical safety of the injectable supplement compound by amino acids and vitamins, administered by intramuscular route in Wistar rats. 56 females (± 220g), pubescent virgins, were randomly divided into seven groups (n=8): Treated with dose of 0.2, 2 and 4 mL, sampled 24 and 96 hours post-treatment (HPT), totaling six groups and one control group (Physiology Standard). Signifi cant increase in the enzymatic activity of serum ALT, AST, LDH and ALP was observed in animals treated with 2 and 4 mL (24 HPT). However, these changes returned to baseline levels 96 HPT, except in serum AST and ALP in animals treated with 4 mL. CK-NAC showed dose-response effect, since the higher compound dose was followed by proportional increase in the circulating levels of this enzyme, associated to muscle degeneration and necrosis area in rats treat with 4mL at 96 HPT. The evaluation of hepatic function did not result in signifi cant changes in the serum levels of triglycerides, cholesterol, albumin, urea and creatinine in the comparison between rats treated with 0.2 mL and control rats, demonstrating the innocuousness of this treatment on the activity of liver and kidney. However, deleterious effects were observed in animals subjected to doses of 2 and 4 mL, including observed increased splenic and hepatosomatic response, signifi cant decrease in circulating albumin levels and signifi cant leukocytosis, which is characterized by neutrophilia, followed by lymphopenia demonstrating the compound irritating effect on muscle tissue.

Clinical safety of amino acids and vitamins administered through parenteral route

Article

Aug 2017

The parenteral use of amino acids and vitamins has been used to improve performance in animal production. However, few studies demonstrating the toxicity of these compounds. The present investigation evaluated the toxicological and clinical safety of the injectable supplement compound by amino acids and vitamins, administered by intramuscular route in Wistar rats. 56 females (± 220g), pubescent virgins, were randomly divided into seven groups (n=8): Treated with dose of 0.2, 2 and 4 mL, sampled 24 and 96 hours post-treatment (HPT), totaling six groups and one control group (Physiology Standard). Signifi cant increase in the enzymatic activity of serum ALT, AST, LDH and ALP was observed in animals treated with 2 and 4 mL (24 HPT). However, these changes returned to baseline levels 96 HPT, except in serum AST and ALP in animals treated with 4 mL. CK-NAC showed dose-response effect, since the higher compound dose was followed by proportional increase in the circulating levels of this enzyme, associated to muscle degeneration and necrosis area in rats treat with 4mL at 96 HPT. The evaluation of hepatic function did not result in signifi cant changes in the serum levels of triglycerides, cholesterol, albumin, urea and creatinine in the comparison between rats treated with 0.2 mL and control rats, demonstrating the innocuousness of this treatment on the activity of liver and kidney. However, deleterious effects were observed in animals subjected to doses of 2 and 4 mL, including observed increased splenic and hepatosomatic response, signifi cant decrease in circulating albumin levels and signifi cant leukocytosis, which is characterized by neutrophilia, followed by lymphopenia demonstrating the compound irritating effect on muscle tissue.

γ-Oryzanol supplementation modifies the inflammatory and oxidative response in fulminant hepatic failure in mice

Article

Oct 2018

The lipopolysaccharide (LPS) and D-galactosamine (D-GalN)-induced hepatotoxicity is a classical model to elucidate the mechanisms and explore potential therapeutic drugs for fulminant hepatic failure (FHF). γ-Oryzanol (γ-ORY) has been showed to possess both antioxidant and anti-inflammatory properties in several pathological models. However, it remains unclear whether γ-ORY could protect against LPS/D-GalN-induced hepatotoxicity. Thus, the aim of the current study was to evaluate the effects of γ-ORY supplementation (for 7 consecutive days) in LPS/D-GalN-induced FHF in mice. One hour after the last supplementation with γ-ORY, the animals received LPS/D-GalN (50 and 500 mg/kg, respectively; i.p.). Twenty-four hours after LPS/D-GalN administration, biochemical assays were performed. LPS/D-GalN administration caused severe histological damage in the liver, such as vascular congestion and megalocytosis, as well as elicited hepatic failure. LPS/D-GalN treatment also caused alterations in liver function, increased levels of oxidative stress and inflammatory markers. In contrast, γ-ORY supplementation protected against histological, oxidative and inflammatory alterations induced by LPS/D-GalN exposure. Collectively, our data supports the notion that both oxidative stress and inflammatory responses are two key pathogenic factors that contribute to LPS/D-GaIN-mediated FHF. Due to its antioxidant and anti-inflammatory actions, our study indicates γ-ORY as a putative pharmacological option to prevent LPS/D-GalN-induced hepatotoxicity.

A Comparative Analysis of the Medicinal Pteridophytes in Turkey, Pakistan, and Malaysia

Chapter

Sep 2018

Pteridophytes are among the oldest land plants, dating back to the Carboniferous period as the dominant type of vegetation. At present these are distributed throughout the world, including tropical, temperate, and Arctic environments, but most of the species are located in tropical regions. They flourish on shady, damp areas, but are also found on rocks and dry grounds, making an important contribution to the earth’s plant diversity. Being the second largest group of vascular plants, they form a significant, dominant component of many plant communities. The pteridophytes are not of major, direct economic importance, with one possible exception. But still, they are found to provide food, medicine, fiber, craft, fuel, and building material and decoration in different cultures of many countries on a global scale. Not much information is available on the economic and medicinal values of this group of plants, when compared to the flowering ones. Main aim of this chapter is to analyze the distribution of traditional knowledge on the medicinally valuable pteridophytes in Turkey, Pakistan, and Malaysia. A total of 103 naturally distributed taxa from this group are used in traditional medicine in these countries. Local people in these countries generally use these as herbal remedies for digestive, respiratory, urogenital, dermatological, cardiovascular, gynecological, ear, nose, and throat, and skeletal-muscular systems; neurological and psychological diseases; and mouth and teeth and other ailments. The three highly prevalent uses of the plants from this group are in Turkey diuretic (10 taxa), kidney stone (10 taxa), and stomachache (8 taxa); in Pakistan wounds (11 taxa), febrifuge (7 taxa), and snake bites (7 taxa); in Malaysia cough (6 taxa), skin diseases (5 taxa), and hair tonic (5 taxa). The comparison reveals that five taxa are used for the same and/or similar applications in Turkey and Pakistan. These taxa are Adiantum capillus-veneris L. (for bronchitis, chest tightness/chest pain, cough, diuretic, expectorant, shortness of breath, and gastrointestinal diseases), Equisetum arvense L. (for cystitis, diabetes, gallbladder diseases/gallstone, hair straighteners/hair tonic, kidney stone, prostate diseases, urinary tract diseases, and wound), E. ramosissimum L. (for diuretic, skin diseases, wound, kidney stone, and sand/renal disorders), Osmunda regalis L. (for rickets and rheumatism), and Pteridium aquilinum (L.) Kuhn. (for intestinal parasites/against worms). Pakistan and Malaysia have only one taxon in common used for the same and/or similar applications, Diplazium esculentum (Retz.) Sw. as tonic. There is no common taxon between Turkey and Malaysia for similar applications. These countries seem to embody a great potential for evaluation of medicinal pteridophytes due to their interesting folk medicine culture.

Clinical safety of amino acids and vitamins administered through parenteral route

Article

Full-text available

Jan 2015

Marco Antonio De Andrade Belo

p>The parenteral use of amino acids and vitamins has been used to improve performance in animal production. However, few studies demonstrating the toxicity of these compounds. The present investigation evaluated the toxicological and clinical safety of the injectable supplement compound by amino acids and vitamins, administered by intramuscular route in Wistar rats. 56 females (± 220g), pubescent virgins, were randomly divided into seven groups (n=8): Treated with dose of 0.2, 2 and 4 mL,sampled 24 and 96 hours post-treatment (HPT), totaling six groups and one control group (Physiology Standard). Signifi cant increase in the enzymatic activity of serum ALT, AST, LDH and ALP was observed in animals treated with 2 and 4 mL (24 HPT). However, these changes returned to baseline levels 96 HPT, except in serum AST and ALP in animals treated with 4 mL. CK-NAC showed dose-response effect,since the higher compound dose was followed by proportional increase in the circulating levels of this enzyme, associated to muscle degeneration and necrosis area in rats treat with 4mL at 96 HPT. The evaluation of hepatic function did not result in signifi cant changes in the serum levels of triglycerides,cholesterol, albumin, urea and creatinine in the comparison between rats treated with 0.2 mL and control rats, demonstrating the innocuousness of this treatment on the activity of liver and kidney. However,deleterious effects were observed in animals subjected to doses of 2 and 4 mL, including observed increased splenic and hepatosomatic response, signifi cant decrease in circulating albumin levels and signifi cant leukocytosis, which is characterized by neutrophilia, followed by lymphopenia demonstrating the compound irritating effect on muscle tissue.</p

Herbal remedies for liver fibrosis: A review on the mode of action of fifty herbs

Article

Full-text available

Nov 2017

Liver fibrosis is a dynamic pathological condition which can be slowed down in its initial phases. Without proper clinical management of fibrosis, progressive liver damage may lead to cirrhosis and ultimately to liver failure or primary liver cancer, which are irreversible conditions. Therefore, in order to cure fibrotic damage to liver, its early stages should be the centre of attention. In this context, some supplements and ‘complementary and alternative medicine (CAM)’ deserve specific mention, because of their already recognized natural way of healing and long lasting curative effects. Moreover, CAM display negligible side effects and hence it is gaining worldwide importance in clinical practices. In particular, herbal medicines are now replacing synthetic pharmaceuticals and looked upon as the sources of novel bioactive substances. To develop satisfactory herbal combinations for treating liver fibrosis, phytoproducts need to be systematically evaluated for their potency as anti-fibrotic, anti-hepatotoxic and antioxidant agents. More importantly, the identified herb/agent should have the remarkable tendency to stimulate hepatocytes regeneration. The present review is a systematic account of at least fifty medicinal herbs and their products which in experimental models have demonstrated antifibrotic activity and thus, most likely candidates to offer therapeutic protection to liver. Nevertheless, much additional work is still needed to explore molecular pathways to discover potential applications of these medicines so as to open up new vistas in biomedical research.

Hepatoprotective effects of ethanol extracts from Folium Syringae against acetaminophen-induced hepatotoxicity in vitro and in vivo

Article

Full-text available

Jul 2017

Background: The leaves of Folium Syringae (FS) have been long used as a traditional Chinese folk medicine for their anti-inflammatory effect, utilized as an antibacterial and antiviral treatment. The purpose of this study was to investigate the potential hepatoprotective effects of FS on acetaminophen-induced hepatic injury in primary hepatocytes and mice. Methods: Hepatocytes obtained by the inverse perfusion method were divided randomly into five groups. Prior to acetaminophen exposure, 3 different doses of FS ethanol extracts were given to hepatocytes and mice, respectively. Thereafter, transaminases, glutathione S-transferase A1 (GSTA1) and some hepatic indices were determined. Results: FS ethanol extracts (200 μg/mL) pretreatment prevented all of the alterations, returning their levels to nearly those levels observed in the control group in vitro. Treatment with FS ethanol extracts (200 mg/kg) significantly reduced the toxicity induced by acetaminophen in vivo, which manifested as a decrease in transaminases, and the hepatoprotective effects of FS were similar to Silymarin (positive group). GSTA1 represented the same change trend as transaminases and hepatic indices, and at a dose of 100 μg/mL FS ethanol extracts in vitro and 100 mg/kg in vivo, GSTA1 content changed significantly (p < 0.01), but transaminases were insignificant (p > 0.05). Conclusion: The results of our investigation suggested that FS ethanol extracts possess significant protective effects against hepatotoxicity induced by acetaminophen both in vitro and in vivo. In addition, GSTA1 could be used as an indicator assessing the extents of hepatic injury, which is more sensitive than transaminases.

Anti-inflammatory and ameliorative effects of gallic acid on fluoxetine-induced oxidative stress and liver damage in rats

Article

Mar 2017

Background: Fluoxetine-induced liver damage is a cause of chronic liver disease. In the present study the hepatoprotective effects of gallic acid against fluoxetine-induced liver damage were examined. Methods: Forty-eight male rats were divided into six groups as follow: group 1, the control group; group 2, rats receiving fluoxetine (24mg/kg bw daily, po) without treatment; group 3, rats receiving 24mg/kg bw fluoxetine, treated with 50mg/kg bw silymarin and groups 4, 5, and 6 in which gallic acid (50, 100, and 200mg/kg bw, po, respectively) was prescribed after the consumption of fluoxetine. The histopathological changes of hepatic tissues were checked out. Results: Fluoxetine caused a significant increase in the levels of serum glutamate oxaloacetate transaminase (GOT), serum glutamate pyruvate transaminase (GPT), lipid profiles, urea, fasting blood sugar (FBS), creatinine (Cr), protein carbonyl (PC) content, malondialdehyde (MDA), and liver TNF-α as an inflammatory element. Also, the obtained results of group 2 revealed a significant decline in ferric reducing ability of plasma (FRAP), liver catalase (CAT), superoxide dismutase (SOD), and vitamin C levels. The treatment with gallic acid showed significant ameliorations in abnormalities of fluoxetine-induced liver injury as represented by the improvement of hepatic CAT, SOD activities, vitamin C levels, serum biochemical parameters, and histopathological changes, in addition to the recovery of antioxidant defense system status. Conclusions: Gallic acid has inhibitory effects on fluoxetine-induced liver damage. The effect of gallic acid is derived from free radical scavenging properties and the anti-inflammatory effect related to TNF-α.

Phytochemicals from fern species: potential for medicine applications

Article

Full-text available

Jun 2017
Phytochemistry Rev

Ferns are an important phytogenetic bridge between lower and higher plants. Historically they have been used in many ways by humans, including as ornamental plants, domestic utensils, foods, and in handicrafts. In addition, they have found uses as medicinal herbs. Ferns produce a wide array of secondary metabolites endowed with different bioactivities that could potentially be useful in the treatment of many diseases. However, there is currently relatively little information in the literature on the phytochemicals present in ferns and their pharmacological applications, and the most recent review of the literature on the occurrence, chemotaxonomy and physiological activity of fern secondary metabolites was published over 20 years ago, by Soeder (Bot Rev 51:442–536, 1985). Here, we provide an updated review of this field, covering recent findings concerning the bioactive phytochemicals and pharmacology of fern species.

Chemical Constituents from Ampelopsis sinica var. hancehPrevent Liver Damage

Article

Mar 2012
LAT AM J PHARM

Antihepatotoxic chemical constituents from the roots of Ampelopsis sinica var. hancei (pl.) W.T. Wang was investigated- Chromatography was used to isolate chemical constituents and their structures were elucidated on the basis of spectroscopic analysis. Antihepatotoxic activity of these compounds in rats was carried out after the establishment of CCl4 induced liver injury. Phytochemical investigation on the roots of Ampelopsis sinica var. hanceh(pl.) W. T. Wang resulted in the isolation of eight compounds including beta-sitosterol (1), beta-daucosterol (2), lupeol (3), trans-resveratrol (4), piceid (5), gallic acid (6), n-butyl gallate (7) and (+)-catechin (8). Rats treated with the compounds 6-8 showed significant (p < 0.05) protection of liver as evidence from normal AST and ALT levels. LDH levels were significantly (p < 0.05) reduced by the treatment with the compounds 5,7 and 8. In addition, MDA levels were significantly (p < 0.05) increased with gallic acid (6) and (+)-catechin (8). All the chemical constituents were isolated from Ampelopsis sinica var. hancei (pl.) W.T. Wang for the first time. Compounds 5-8 showed significantly antihepatotoxtic activity in CCl4-induced liver damage rats.

Evaluation of Hepato protective activity of ethanolic root extract of Punica granatum

Article

Jan 2013

Objective: The present study was aimed to evaluate the protective effect of the ethanolic root extract of Punica granatum on carbon tetrachloride induced hepatotoxicity. Methods: The extract was evaluated for hepatoprotective activity against CCl4-induced hepatotoxicity using rat liver. Hepatic enzymes studied include Alanine amino transferase (ALT), aspartate amino transferase (AST) and alkaline phosphatase (ALP). Hepatic injuries involved with possible necrosis which may have contributed to increase level of hepatic enzyme levels. Punica granatum root extract was administered orally by dissolving in water. The root extract was screened for toxicity by oral toxicity studies according to OECD guidelines 423. LD50 was calculated for selection of dose. Liver was excised and histopathological study was conducted by keeping in 10% formalin. They were stained with haematoxyline and eosin and photographed. Results: Results showed that treatment with ethanolic root extract of Punica granatum normalization of cells and reduced sinusoidal dilation along with mild inflammogens which are compared with Silymarin. This was evident from significant reduction in P<0.05, P<0.01, P<0.001 in serum enzyme levels. In the hepatoprotective and curative period, the highest damages in liver tissue were found in the order Carbon tetrachloride > low dose > high dose> silymarin> normal control. This clearly explained the reason for the Hepato protective activity of pomegranate root extract. Conclusion: It was concluded from the result that the ethanolic extract of Punica granatum root possesses hepatoprotective activity.

Pharmacological potential of Silymarin in combination with hepatoprotective plants against experimental hepatotoxicity in rats

Article

Mar 2012

The present study was designed to investigate the synergistic hepatoprotective effect of Silymarin in combination with standardised extracts of Picrorrhiza kurroa, Phyllanthus amarus, Tephrosia purpurea, Asparagus racemosus plants against experimental hepatotoxicity induced by administration of Paracetamol (3g/kg; p.o) and Carbontetrachloride (1ml/kg; s.c) in wistar rats. Paracetamol and CCl 4 intoxications caused increase in SGPT, SGOT, ALP, bilirubin, TBARS, Nitrate/Nitrite content and decrease in Glutathione, Na +K +ATPase level in rats. However, pretreatment by three different doses of Silymarin-12.5, 25 and 50 mg/kg alone, and combination of Silymarin-25 mg/kg with each plant extracts (50 mg/kg) significantly reversed the effect of these hepatotoxicants and further resulted in decrease inflammatory cell infiltration, vacuolization and centrilobular necrosis as revealed by histological findings of rat liver in present study. This study demonstrates the potentiation of cellular protective mechanisms like anti-oxidative, anti-inflammatory, membrane stabilization effects of silymarin with inclusion of hepatoprotective plants in experimental hepatotoxicity in rat.

HEPATOPROTECTIVE MEDICINAL HERBS AND ANIMAL MODELS FOR THEIR SCREENING -A REVIEW

Article

Dec 2015

The liver is a vital solid organ in the upper abdomen that helps in digestion, detoxification and has other synthetic, metabolic and storage functions. Liver diseases are a major problem worldwide; viral hepatitis, alcohol, malnutrition, autoimmune and drugs being most important causes. Currently there is no way to compensate for the absence of liver function in the long term and liver transplant is the only option for those with irreversible loss of hepatic function. The scientific basis for the statement that plants and their active constituents play an important role in the prevention of diseases is continuously advancing. In this review some of the plants with their phyto-constituents studied for protective effect in liver diseases are reviewed.

Phenolic composition, DNA damage protective activity and hepatoprotective effect of free phenolic extract from Sphallerocarpus gracilis seeds

Article

Mar 2014

The phenolic composition of the free phenolic extract from Sphallerocarpus gracilis seeds was analyzed by HPLC-MS and predominant compounds were chlorogenic acid, di-caffeoylquinic acid glucoside and luteolin-7-O-glucoside. The free phenolic extract was evaluated for DNA damage protective activity induced by ROO and OH radicals and hepatoprotective effect in vivo and in vitro. Results revealed that the free phenolic extract exhibited significant protective activity against both ROO and OH radical-induced DNA damage and the phenolic extract exerted more potent inhibitory activity against OH radical-induced damage than against that induced by ROO radicals. In vivo experimental results showed that the phenolic extract significantly prevented the increase of serum alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase activities and hepatic malondialdehyde level caused by CCl4 in rats, and markedly increased hepatic superoxide dismutase, catalase and glutathione peroxidase levels. Histopathological examinations further confirmed that the phenolic extract could protect the liver from CCl4-induced damage. In vitro experimental results showed that the phenolic extract could reduce BRL hepatocyte apoptosis and damage induced by CCl4. These findings indicate that the S. gracilis seed could be developed as a medicinal herb for the therapy and prevention of hepatic injury.

Preventive and curative effect of methanolic extract of Gardenia gummifera Linn. f. on thioacetamide induced oxidative stress in rats

Article

Apr 2012

Objective To evaluate the antioxidant and antihepatotoxic effect of methanolic extract of Gardenia gummifera Linn. f. root (MEGG) on thioacetamide (TAA) induced oxidative stress in male Wistar rats.Methods In the preventive study, rats were administered with 125 and 250 mg/kg of MEGG for 9 days prior to TAA administration (100 mg/kg s.c.). In post-treatment groups, rats were treated with MEGG at doses of 125 and 250 mg/kg, 2, 24 and 48 h after TAA intoxication. Silymarin was used as a standard drug control (100 mg/kg). Hepatotoxicity was assessed by quantifying the serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH). The antioxidant potential of MEGG was evaluated by the estimation of catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), reduced glutathione (GSH) and lipid peroxidation [thiobarbituric acid reactive substances (TBARS)] in hepatic and renal tissues. Histopathological changes were also evaluated.ResultsMEGG significantly (P≤0.05) prevented the elevation of serum AST, ALT, ALP, LDH and tissue malondialdehyde levels in both experimental groups, when compared to the TAA alone treated groups. The rats receiving TAA plus MEGG exhibited significant (P≤0.05) increases in hepatic and renal antioxidant activities including GSH, GST, GR, GPx and CAT levels. Quantification of histopathological changes also supported the dose dependent protective effects of MEGG.Conclusions These observations suggest that MEGG has dose dependent hepatoprotective and antioxidant effect against TAA induced oxidative stress.

Acute and subacute toxicity studies of Lygodium flexuosum extracts in rats

Article

Jan 2012

Objective To investigate the acute and subacute toxicity of Lygodium flexuosum (L. flexuosum) extracts to substantiate the tribal or folk claims for its use as a safe hepatoprotective drug.Methods The water, ethanol and n-hexane extracts of L. flexuosum were tested in vivo in Wistar rats. In acute toxicity model, rats received a single dose (5 g/kg) of water extract, ethanol extract, and n-hexane extract of L. flexuosum and kept under observation for 14 d. In subacute toxicity studies, animals were treated with daily doses (1 g/kg body weight) of water, ethanol and n-hexane extract respectively for 30 d.ResultsIn acute toxicity, the extracts administration up to a higher dose of 5 g/kg did not result in mortality or any change in behavior and biochemical parameters of the animals. Sub acute toxicity studies in rats showed that treatment with the extracts did not alter the serum biochemical and hematological parameters.Conclusions The extracts were found to be devoid of any toxicity in acute (5 g/kg) and subacute (1 g/kg) toxicity evaluation in rats.

Curative effect of Amorphophallus campanulatus (Roxb.) Blume. tuber methanolic extract against thioacetamide induced oxidative stress in experimental rats

Article

Jan 2012

Objective To evaluate the curative effect of the methanolic extract of Amorphophallus campanulatus (A. campanulatus) tuber (ACME) against thioacetamide induced oxidative stress in rats.Methods The curative potential of two different doses of ACME (125 and 250 mg/kg; p.o.) was evaluated against thioacetamide (TAA) induced oxidative stress in male Wistar rats. Single dose of TAA (100 mg/kg; s.c.) was administered to the rats in all groups except the normal control. In treatment groups, rats were administered with silymarin-the standard drug (100 mg/kg; p.o.) and ACME 2, 24 and 48 h after TAA intoxication. Hepatotoxicity was assessed by quantifying the serum levels of AST, ALT, ALP and LDH. The antioxidant potential of ACME were also evaluated by the estimation of catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), reduced glutathione (GSH) and lipid peroxidation (Thiobarbituric Acid Reactive Substances-TBARS) in hepatic and renal tissues. In addition, the liver sections were also evaluated for its histopathologic changes.ResultsACME significantly (P<0.05) reversed the elevation of serum AST, ALT, ALP, LDH and tissue malondialdehyde levels. Hepatic and renal GSH, GST, GR, GPx and catalase levels were remarkably increased by the treatment with the extract. Quantification of histopathological changes also supported the dose dependent curative effects of ACME.Conclusion This study demonstrates the antioxidant and hepatoprotective activity of ACME and thus scientifically supports the use of this tuber in traditional medicine for the treatment of liver disorders.

Preventive and curative effect of Woodfordia fruticosa Kurz flowers on thioacetamide induced oxidative stress in rats

Article

Nov 2011

Objective To evaluate the preventive and curative effect of Woodfordia fruticosa (W. fruticosa) Kurz flowers on thioacetamide induced oxidative stress in rats.Methods Two different doses of methanolic extract of W. fruticosa (MEWF 100 mg/kg and 200 mg/kg) were used to study the antioxidant activity in experimental rats against thioacetamide (TAA) induced oxidative stress in preventive and curative models. Single dose of TAA (100 mg/kg; s.c.) was administered to the rats in all groups except the normal control. Various serum enzymes like aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and Lactate dehydrogenase (LDH) were studied. The antioxidant status of liver and kidney were evaluated by the following parameters like catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), reduced glutathione (GSH) and malondialdehyde (MDA). Histopathological changes of liver tissue were also evaluated.ResultsMEWF significantly (P<0.05) prevented and reversed the elevation of serum AST, ALT, ALP, LDH, and tissue malondialdehyde levels in both the experimental models. Hepatic and renal GSH, GST, GR, GPx, and catalase levels were remarkably increased by the treatment with the extract in both the experimental models. In the case of MDA the hepatic and renal levels were decreased by the treatment with the extract.Conclusion This study demonstrates the protective and curative effects of MEWF, and thus scientifically supports the use of this plant in traditional medicine for the treatment of liver disorders.

Protective effect of extracts from dates (Phoenix dactylifera L.) on carbon tetrachloride-induced hepatotoxicity in rats

Article

Full-text available

Jul 2009

Bioflavonoids classification, pharmacological, biochemical effects and therapeutic potential

Article

Full-text available

Jan 2001
INDIAN J PHARMACOL

Flavonoids belong to a group of polyphenolic compounds, which are classified as flavonols, flavonones, flavones, flavanols, flavan-3-ols and isoflavones according to the positions of the substitutes present on the parent molecule. Flavonoids of different classes have several pharmacological activities. Flavonoids have also been known to posses biochemical effects, which inhibit a number of enzymes such as aldose reductase, xanthine oxidase, phosphodiesterase, Ca +2 -ATPase, lipoxygenase, cycloxygenase, etc. They also have a regulatory role on different hormones like estrogens, androgens and thyroid hormone. In view of their wide pharmacological and biological actions, they seem to be having a great therapeutic potential. Flavonoids biochemistry pharmacology therapeutic potential SUMMARY

Notable pertinence of Lygodium flexuosum (L.) Sw. in tribal medicine of India and ethnopharmacognostical investigation

Article

Jan 2002

K. Kumar

Pathologic diagnosis of liver disease

Article

Jan 1996

J.H. Lefkowitch

Enzymes in hepatic disease, Lea and Febiger

Article

Jan 1970

Clinical aspects of liver disease caused by industrial and environmental toxins

Article

Jan 1993

N. Gitlin

Development of phytomedicine for liver diseases

Article

Jun 1999
INDIAN J PHARMACOL

A phytotherapeutic approach to modern drug development can provide many invaluable drugs from traditional medicinal plants. Search for pure phytochemicals as drugs is time consuming and expensive. Numerous plants and polyherbal formulations are used for the treatment of liver diseases. However, in most of the severe cases, the treatments are not satisfactory. Although experimental evaluations were carried out on a good number of these plants and formulations, the studies were mostly incomplete and insufficient. The therapeutic values were tested against a few chemicals-induced subclinical levels of liver damages in rodents. Even common dietary antioxidants can provide such protection from liver damage caused by oxidative mechanisms of toxic chemicals. However, experiments have clearly shown that plants such as Picrorrhiza kurroa, Andrographis paniculata, Eclipta alba, Silibum marianum, Phyllanthus maderaspatensis and Trichopus zeylanicus are sufficiently active against, at least, certain hepatotoxins. Screening plants for antihepatitis activities remains in its infancy. P. kurroa, E. alba, Glycyrrhiza glabra, A. paniculata and P. amarus are likely to be active against Hepatitis B virus. In the case of severe liver damage, most of the liver cells die or turn into fibrotic state. In this case, the treatment should include in addition to the therapeutic agents, agents which can stimulate liver cell proliferation. For developing satisfactory herbal combinations to treat severe liver diseases, plants have to be evaluated systematically for properties such as antiviral activity (Hepatitis B, Hepatitis C, etc), antihepatotoxicity (antioxidants and others), stimulation of liver regeneration and choleretic activity. The plants with remarkable activities for each of the above properties have to be identified. Single plant may not have all the desired activities. A combination of different herbal extracts/'fractions is likely to provide desired activities to cure severe liver diseases. Development of such medicines with standards of safety and efficacy can revitalise treatment of liver disorders. hepatoprotective activity.

IFCC methods for the measurement of catalytic concentrations of enzymes Part 3. IFCC method for alanine aminotransferase (L-alanine: 2-oxoglutarate aminotransferase, EC 2.6.1.2)

Article

Jul 1980
CLIN CHIM ACTA

H.U. Bergmeyer

Extraction and Identification of Antioxidative Components of Hsian-tsao ( Mesona procumbens Hemsl.)

Article

Aug 2001
LWT-FOOD SCI TECHNOL

The antioxidative activities of various solvent extracts of Hsian-tsao (Mesona procumbens Hemsl.) were investigated. The results showed that for the same concentration of 0.2 g/kg, the antioxidative activities of various Hsian-tsao extracts, especially the ethyl acetate extract, which exhibited 93% inhibition of peroxidation of linoleic acid, were greater than those of BHA and α -tocopherol. When the ethyl acetate extract of Hsian-tsao (EEHT) was separated into nine fractions by silica gel chromatography, fraction II showed high yield and high antioxidative activity. Fraction II was further separated into five subfractions using silica gel chromatography. Subfraction IIC was then isolated by preparative HPLC equipped with a silica column and four components were identified as stigmasterol, β -sitosterol, oleanolic acid, and ursolic acid by UV, EI-MS,1H-, and13SC-NMR. The descending order of antioxidative activity for those compounds was: EEHT>BHA>α -tocopherol>ursolic acid>oleanolic acid>β -sitosterol>stigmasterol.

IFCC method for aspartate aminotransferase. Appendix A. Description of pertinent factors in obtaining optimal conditions for measurement

Article

Aug 1976
CLIN CHIM ACTA

Assay for Lipid Peroxides in Animal Tissues by Thiobarbituric Acid Reaction

Article

Jul 1979

The reaction of lipid peroxides in animal tissues with thiobarbituric acid was dependent on pH of the reaction mixture as was the case for linoleic acid hydroperoxide. The optimum pH was found to be 3.5. Taking this fact into consideration, a standard procedure for the assay of lipid peroxide level in animal tissues by their reaction with thiobarbituric acid was developed as follows. Ten percent ( tissue homogenate was mixed with sodium dodecyl sulfate, acetate buffer (pH 3.5), and aqueous solution of thiobarbituric acid. After heating at 95°C for 60 min, the red pigment produced was extracted with n-butanol-pyridine mixture and estimated by the absorbance at 532nm. As an external standard, tetramethoxy-propane was used, and lipid peroxide level was expressed in terms of nmol malondialdehyde. Using this method, the liped peroxide level in the liver of rats suffering from carbon tetrachloride intoxication was investigated. The results were in good agreement with previously reported data obtained by measuring diene content.

Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver

Article

Feb 1979
Biochim Biophys Acta

Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver have been investigated. After perfusing the lung to remove contaminating blood, this organ was found to have an apparent concentration of glutathione (2mM) which is approx. 20% of that found in the liver. Both organs contain very low levels of glutathione disulfide. Neither phenobarbital nor methylcholanthrene had a significant effect on the levels of reduced glutathione in lung and liver. In addition, the activities of some glutathione-metabolizing enzymes--glutathione reductase and glutathione S-transferase activity assayed with four different substrates--were observed to be 5-to 60-fold lower in lung tissue than in the liver.

Provisional recommendations on IFCC methods for the measurement of catalytic concentrations of enzymes Part 2. IFCC method for aspartate aminotransferase

Article

Aug 1976
CLIN CHIM ACTA

Mechanisms of Carbon Tetrachloride Hepatotoxicity

Article

Feb 1989

Gary A Clawson

CCI4 has long served as a model compound for study of hepatotoxicity. While its simple chemical structure held the allure of a simple mechanism of action, decades of study have disclosed a complex series of responses. Significant early damage following CCI4 administration includes: (1) A number of alterations affecting Ca2+ homeostasis, which conspire to redistribute cellular Ca2+ from endoplasmic reticulum and mitochondria to cytosol, and (2) hypomethylation of ribosomal RNA, which disrupts protein synthesis. The genesis of the injury in vivo appears to encompass early 'metabolism-dependent' effects (which appear to be largely independent of CCI4 concentration at the levels studied) and later 'metabolism-independent' effects, which parallel CCI4 concentration. The inability of injured hepatocytes to respond anabolically to early damage may be a critical feature in CCI4 hepatotoxicity.

Carbon Tetrachloride Hepatotoxicity: An Example of Lethal Cleavage

Article

Dec 1973
CRC Crit Rev Toxicol

Mechanism of fatty liver in protein deficiency. An experimental study in the rhesus monkey

Article

Apr 1972
GASTROENTEROLOGY

Solid-phase extraction and gas chromatography mass spectrometry determination of kaempferol and quercetin in human urine after consumption of Ginkgo biloba tablets

Article

Mar 1999
J Chrom B Biomed Sci Appl

A method was developed for the quantification of the flavonoids quercetin and kaempferol in human urine using a solid-phase extraction procedure followed by gas chromatography-mass spectrometry. Deuterated internal standards of the analytes were spiked into the samples prior to extraction. The limit of detection of the method was ca. 10 pg on column and precision of the method for quantification in a sample of urine was +/-9.40% for kaempferol and +/-7.34% for quercetin (n = 6). The levels of quercetin and kaempferol found in urine samples were only a small fraction of the amount ingested. The treatment of urine samples with beta-glucuronidase markedly increased the levels of flavonoids detected, supporting the view that kaempferol and quercetin are eliminated in the urine as glucuronides.

Height and breast cancer risk--the bias of self-reported versus measured results. Comments on height and breast cancer risk, Tavani et al., Eur J Cancer 1998, 34, 543-547

Article

Feb 1999
EUR J CANCER

Induction of Apoptosis by Apigenin and Related Flavonoids Through Cytochrome c Release and Activation of Caspase-9 and Caspase-3 in Leukaemia HL-60 Cells

Article

Oct 1999
EUR J CANCER

The aim of this study was to investigate the mechanism of flavonoid-induced apoptosis in HL-60 leukaemic cells. Thus, the effect of structurally related flavonoids on cell viability, DNA fragmentation and caspase activity was assessed. Loss of membrane potential and reactive oxygen species generation were also monitored by flow cytometry. The structurally related flavonoids, such as apigenin, quercetin, myricetin, and kaempferol were able to induce apoptosis in human leukaemia HL-60 cells. Treatment with flavonoids (60 microM) caused a rapid induction of caspase-3 activity and stimulated proteolytic cleavage of poly-(ADP-ribose) polymerase (PARP). Furthermore, these flavonoids induced loss of mitochondrial transmembrane potential, elevation of reactive oxygen species (ROS) production, release of mitochondrial cytochrome c into the cytosol, and subsequent induction of procaspase-9 processing. The potency of these flavonoids on these features of apoptosis were in the order of: apigenin > quercetin > myricetin > kaempferol in HL-60 cells treated with 60 microM flavonoids. These results suggest that flavonoid-induced apoptosis is stimulated by the release of cytochrome c to the cytosol, by procaspase-9 processing, and through a caspase-3-dependent mechanism. The induction of apoptosis by flavonoids may be attributed to their cancer chemopreventive activity. Furthermore, the potency of flavonoids for inducing apoptosis may be dependent on the numbers of hydroxyl groups in the 2-phenyl group and on the absence of the 3-hydroxyl group. This provides new information on the structure-activity relationship of flavonoids.

5′-Methylthioadenosine administration prevents lipid peroxidation and fibrogenesis induced in rat liver by carbon-tetrachloride intoxication

Article

Apr 2001
J HEPATOL

5'-Methylthioadenosine (MTA), a product of S-adenosylmethionine (SAM) catabolism, could undergo oxidation by mono-oxygenases and auto-oxidation. MTA and SAM effects on oxidative liver injury were evaluated in CCl4-treated rats. Male Wistar rats were killed 1-48 h after poisoning with a single intraperitoneal CCl4 dose (0.15 ml/100 g) or with the same dose twice a week for 14 weeks. Daily doses of MTA or SAM (384 micromol/kg), started 1 week before acute CCl4 administration or with chronic treatment, were continued up to the time of sacrifice. Acute and chronic CCl4 intoxication decreased MTA and, to a lesser extent, SAM and reduced glutathione (GSH) liver levels. MTA administration increased liver MTA without affecting SAM and GSH. SAM treatment caused complete/partial recovery of these compounds. MTA and, to a lesser extent, SAM prevented an increase in liver phospholipid hydroperoxides in acutely and chronically intoxicated rats and in prolyl hydroxylase activity and trichrome-positive areas in chronically treated rats. MTA prevented upregulation of Tgf-beta1, Collagen-alpha1 (I) and Tgf-alpha genes in liver of chronically intoxicated rats, and TGF-beta1-induced transdifferentiation to myofibroblasts and growth stimulation by platelet-derived growth factor-b of stellate cells in vitro. MTA and SAM protect against oxidative liver injury through partially different mechanisms.

Early gene expression of hepatocyte growth factor in mononuclear phagocytes of rat liver after administration of carbon tetrachloride

Article

Jan 2003

Hepatocyte growth factor (HGF) is a potent hepatocyte mitogen supposed to be a main stimulant of hepatocyte replication during liver regeneration. During acute liver injury, HGF has been detected in nonparenchymal cells of the liver. We performed in situ hybridization of HGF in rat livers after administration of carbon tetrachloride (CCl4). Mononuclear phagocytes (MNP) were isolated from normal and injured livers and HGF expression was analyzed by Northern blotting, in situ hybridization, and immunoprecipitation of 35S-labeled proteins. In situ hybridization of normal liver revealed few HGF positive cells within hepatic sinusoids. In injured livers, the number of cells containing HGF transcripts was increased at 6-24 h after CCl4. Hepatocyte growth factor transcripts in MNP from normal liver were detectable in trace amounts, but became clearly detectable at 6 h and persisted up to 24 h after CCl4 administration. In situ hybridization of MNP isolated from normal liver did not reveal positive cells. Mononuclear phagocytes became HGF-positive when isolated 6 h after CCl4. Hepatocyte growth factor protein was detected in MNP isolated 24 h after CCl4. Hepatocyte growth factor in MNP is not directly induced by interferon-alpha, interferon-gamma or tumour necrosis factor-alpha (TNF-alpha). Stimulated resident mononuclear phagocytes may play a significant role in the increase of HGF expression in liver regeneration after acute liver injury.

Hepatotoxicity and Mechanism of Action of Haloalkanes: Carbon Tetrachloride as a Toxicological Model

Article

Feb 2003

The use of many halogenated alkanes such as carbon tetrachloride (CCl4), chloroform (CHCl3) or iodoform (CHI3), has been banned or severely restricted because of their distinct toxicity. Yet CCl4 continues to provide an important service today as a model substance to elucidate the mechanisms of action of hepatotoxic effects such as fatty degeneration, fibrosis, hepatocellular death, and carcinogenicity. In a matter of dose,exposure time, presence of potentiating agents, or age of the affected organism, regeneration can take place and lead to full recovery from liver damage. CCl4 is activated by cytochrome (CYP)2E1, CYP2B1 or CYP2B2, and possibly CYP3A, to form the trichloromethyl radical, CCl3*. This radical can bind to cellular molecules (nucleic acid, protein, lipid), impairing crucial cellular processes such as lipid metabolism, with the potential outcome of fatty degeneration (steatosis). Adduct formation between CCl3* and DNA is thought to function as initiator of hepatic cancer. This radical can also react with oxygen to form the trichloromethylperoxy radical CCl3OO*, a highly reactive species. CCl3OO* initiates the chain reaction of lipid peroxidation, which attacks and destroys polyunsaturated fatty acids, in particular those associated with phospholipids. This affects the permeabilities of mitochondrial, endoplasmic reticulum, and plasma membranes, resulting in the loss of cellular calcium sequestration and homeostasis, which can contribute heavily to subsequent cell damage. Among the degradation products of fatty acids are reactive aldehydes, especially 4-hydroxynonenal, which bind easily to functional groups of proteins and inhibit important enzyme activities. CCl4 intoxication also leads to hypomethylation of cellular components; in the case of RNA the outcome is thought to be inhibition of protein synthesis, in the case of phospholipids it plays a role in the inhibition of lipoprotein secretion. None of these processes per se is considered the ultimate cause of CCl4-induced cell death; it is by cooperation that they achieve a fatal outcome, provided the toxicant acts in a high single dose, or over longer periods of time at low doses. At the molecular level CCl4 activates tumor necrosis factor (TNF)alpha, nitric oxide (NO), and transforming growth factors (TGF)-alpha and -beta in the cell, processes that appear to direct the cell primarily toward (self-)destruction or fibrosis. TNFalpha pushes toward apoptosis, whereas the TGFs appear to direct toward fibrosis. Interleukin (IL)-6, although induced by TNFalpha, has a clearly antiapoptotic effect, and IL-10 also counteracts TNFalpha action. Thus, both interleukins have the potential to initiate recovery of the CCl4-damaged hepatocyte. Several of the above-mentioned toxication processes can be specifically interrupted with the use of antioxidants and mitogens, respectively, by restoring cellular methylation, or by preserving calcium sequestration. Chemicals that induce cytochromes that metabolize CCl4, or delay tissue regeneration when co-administered with CCl4 will potentiate its toxicity thoroughly, while appropriate CYP450 inhibitors will alleviate much of the toxicity. Oxygen partial pressure can also direct the course of CCl4 hepatotoxicity. Pressures between 5 and 35 mmHg favor lipid peroxidation, whereas absence of oxygen, as well as a partial pressure above 100 mmHg, both prevent lipid peroxidation entirely. Consequently, the location of CCl4-induced damage mirrors the oxygen gradient across the liver lobule. Mixed halogenated methanes and ethanes, found as so-called disinfection byproducts at low concentration in drinking water, elicit symptoms of toxicity very similar to carbon tetrachloride, including carcinogenicity.

Serum Enzymes in Hepatic Disease

Article

Apr 1959
MED CLIN N AM

Serum Lactic Dehydrogenase Activity: An Analytical Assessment of Current Assays

Article

Sep 1963

Serum LDH activities assayed spectrophotometrically by the "forward" (lactate + DPN to pyruvate + DPNH + H) method have linear reaction rates, activity proportional to the amount of serum added, and a reproducibility of 1.3%. The reagent mixture can be stored frozen for 6 months and in the lyophilized state indefinitely. Poor separation of normal from abnormal serum LDH activities results from the nonlinear calibration curves and decreasing reaction rates of the "backward" spectro-photometric assay. The dinitrophenylhydrazine colorimetric assay is deemed unsuitable for clinical use because large variations in activity result from minor variations in the reagent calibration curve, and because colorimetric activities are inaccurate as compared to activities obtained with the "forward" spectrophotometric assay.

Further studies on the antihepatotoxic activity of phyllanthus maderaspatensis LINN

Article

Jun 2004
J ETHNOPHARMACOL

Phyllanthus maderaspatensis (whole plant extracts) was evaluated for its antihepatotoxic and choleretic activities in rats. The plant extracts (200 mg/kg, n-hexane, ethyl alcohol or water) showed a remarkable hepatoprotective activity against acetaminophen-induced hepatotoxicity as judged from the serum marker enzymes. The water and ethyl alcohol extracts showed moderate activity compared to the n-hexane extract, which showed activity at a dose as low as 1.5 mg/kg. The antihepatotoxicity of the hexane extract was found to be better than silymarin, a standard hepatoprotective herbal drug. The effect of n-hexane extract was found to be concentration-dependent. This extract also exhibited choleretic activity in normal rats, and in vitro hydroxyl radical scavenging activity and inhibition of lipid peroxidation.

Evaluation of hepatoprotective effect of Amalkadi Ghrita against carbon tetrachloride-induced hepatic damage in rats

Article

Mar 2004
J ETHNOPHARMACOL

Amalkadi Ghrita (AG), a polyherbal formulation, was evaluated for its hepatoprotective activity against carbon tetrachloride (CCl4)-induced hepatic damage in rats. The hepatoprotective activity of AG was evaluated by measuring levels of serum marker enzymes like serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP), and acid phosphatase (ACP). The serum levels of total proteins and bilirubin were also estimated. The histological studies were also carried out to support the above parameters. Silymarin was used as standard drug. Administration of AG (100 and 300 mg/kg, p.o.) markedly prevented CCl4-induced elevation of levels of serum GPT, GOT, ACP, ALP, and bilirubin. The decreased level of total proteins due to hepatic damage induced by CCl4 was found to be increased in AG-treated group. The results are comparable to that of silymarin. A comparative histopathological study of liver exhibited almost normal architecture, as compared to CCl4-treated group. Hepatoprotective effect of AG is probably due to combined action of all ingredients.

Free Radical Scavenging and Hepatoprotective Actions of the Medicinal Herb, Crassocephalum crepidioides from the Okinawa Islands

Article

Feb 2005

Free radical scavenging and protective actions against chemically induced hepatotoxicity of Crassocephalum crepidioides were investigated. A water extract of C. crepidioides strongly scavenged superoxide anion, hydroxyl radical and also stable radical 1,1-diphenyl-2-picrylhydrazyl. Galactosamine (GalN, 400 mg/kg) and lipopolysaccharide (LPS, 0.5 microg/kg) induced hepatotoxicity of rats as seen by an elevation of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and of lipid peroxidation in liver homogenates was significantly depressed when the herbal extract was given intraperitoneally 1 and 15 h before GalN and LPS treatment. Similarly, carbon tetrachloride (CCl4) induced liver injury as evidenced by an increase in AST and ALT activities in serum was also inhibited by the extract pretreatment. Isochlorogenic acids, quercetin and kaempferol glycosides were identified as active components of C. crepidioides with strong free radical scavenging action. These results demonstrate that C. crepidioides is a potent antioxidant and protective against GalN plus LPS- or CCl4-induced hepatotoxicity.

Hepatoprotective effects of rubiadin, a major constituent of Rubia cordifolia Linn

Article

Mar 2006
J ETHNOPHARMACOL

The hepatoprotective effects of rubiadin, a major constituent isolated from Rubia cordifolia Linn., were evaluated against carbon tetrachloride (CCl4)-induced hepatic damage in rats. Rubiadin at a dose of 50, 100 and 200 mg/kg was administered orally once daily for 14 days. The substantially elevated serum enzymatic activities of serum glutamic oxaloacetic transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), serum alkaline phosphatase (SALP) and gamma-glutamyltransferase (gamma-GT) due to carbon tetrachloride treatment were dose dependently restored towards normalization. Meanwhile, the decreased activities of glutathione S-transferase and glutathione reductase were also restored towards normalization. In addition, rubiadin also significantly prevented the elevation of hepatic malondialdehyde formation and depletion of reduced glutathione content in the liver of CCl4 intoxicated rats in a dose dependent manner. Silymarin used as standard reference also exhibited significant hepatoprotective activity on post treatment against carbon tetrachloride induced hepatotoxicity in rats. The biochemical observations were supplemented with histopathological examination of rat liver sections. The results of this study strongly indicate that rubiadin has a potent hepatoprotective action against carbon tetrachloride induced hepatic damage in rats.

Preventive and curative effect of Lygodium flexuosum (L.) Sw. on carbon tetrachloride induced hepatic fibrosis in rats

Article

Sep 2006
J ETHNOPHARMACOL

The preventive and curative effect of Lygodium flexuosum on experimentally induced hepatic fibrosis by carbon tetrachloride (CCl(4)) was evaluated in rats. Hepatic fibrosis was induced in male Wistar rats by CCl(4) administration (150 microL/100g rat weight, oral) twice a week for 10 weeks. In preventive treatment daily doses of Lygodium flexuosum n-hexane extract (200 mg/kg, p.o) was administered for 10 weeks. In curative treatment Lygodium flexuosum extract (200 mg/kg, p.o) was given for 2 weeks after the establishment of fibrosis for 10 weeks. Treatment with CCl(4) caused a significant decrease in body and liver weight. Lygodium flexuosum n-hexane extract prevented or reversed the decline in body and liver weight. Treatment with the extract prevented or restored the elevation of serum AST, ALT and LDH levels. Lygodium flexuosum treatment remarkably prevented or reversed an increase in liver hydroxyproline content in chronically treated rats. Histopathological changes of hepatic lesions induced by CCl(4) were significantly (p < or = 0.05) improved by treatment with Lygodium flexuosum. These results support that Lygodium flexuosum exerts effective protection in carbon tetrachloride induced hepatic fibrosis in rats.

Ethno-medico-botany of the Southern Western Ghats of India Ethnobiology in Human Welfare Extraction and identification of antioxidative components of Hsian-tsao (Mesona procumbens Hemsl

Jan 1994
173-180

A N Henry
V B Hosagoudar
K Ravikumar
C Y Hung
G C Yen

Henry, A.N., Hosagoudar, V.B., Ravikumar, K., 1996. Ethno-medico-botany of the Southern Western Ghats of India. In: Jain, S.K., (Ed.), Ethnobiology in Human Welfare. Deep Publications, New Delhi, pp. 173–180, Proceedings of IV International Congress of Ethnobiology, Lucknow, India, November 17–21, 1994. Hung, C.Y., Yen, G.C., 2001. Extraction and identification of antioxidative components of Hsian-tsao (Mesona procumbens Hemsl.). Lebensm. Wiss. Technol. 34, 306–311.

Mechanisms of chemically induced liver disease

Jan 1996
875

Dahm

Dahm, J.L., Jones, P.D., 1996. Mechanisms of chemically induced liver dis-ease. In: Zakim, D., Boyer, T.D. (Eds.), Hepatology—A Textbook of Liver Disease. WB Saunders, Philadelphia, pp. 875–890.

Dictionary of Indian Folk Medicine and Ethnobotany. Deep publications

Jan 1991
120

S K Jain

Jain, S.K., 1991. Dictionary of Indian Folk Medicine and Ethnobotany. Deep publications, New Delhi, p. 120.

Ethno-medico-botany of the Southern Western Ghats of India

A N Henry
V B Hosagoudar
K Ravikumar

Early gene expression of hepatocytes growth factor in mononuclear phagocytes of rat liver after administration of carbon tetrachloride

Jan 2002
486

Armburst

Protective effect of Lygodium flexuosum (L.) Sw. extract against carbon tetrachloride-induced acute liver injury in rat

Abstract

No full-text available

Recommended publications

Improved biopharmaceutical properties of carvedilol employing α-tocopheryl polyethylene glycol 1000...

Antioxidant and hepatoprotective activity of chloroform and ethanol extracts of Gmelina asiatica aer...

Evaluation of the Protective Potential of Chromolaena odorata Linn. Extract on Carbon Tetrachloride-...

Allium tuberosum : Antidiabetic and hepatoprotective activities