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Dandelion-enriched diet of mothers alleviates lead-induced damages in liver of newborn rats
Abstract
Lead (Pb) is a highly toxic metal present in the environment. It causes disturbances of several functions, including hematologic, renal, reproductive and nervous ones. Preventive or curative use of medicinal plants against these disorders may be a promising and safe therapeutic strategy. This study evaluated the hepatic toxic effects of prenatal exposure to lead in rats and the possible protective effect of dandelion (Taraxacum officinale) added to the diet. Female rats were given a normal diet (control) or a diet enriched with dandelion (treated). In addition, lead acetate was administered to half of the rats through drinking water from the 5th day of gestation until the 14th day postpartum. Lead toxicity was evaluated in their offspring by measuring body and liver weights, plasma biochemical parameters, liver damage, as well as protein content and activities of antioxidant enzymes in the liver tissues. Lead poisoning of mothers caused lead deposition in blood and stomach of their pups as well as hepatic tissue damages. Moreover, significant decreases in liver weight and protein content were found. Lead treatment caused oxidative stress and marked changes in the activity of antioxidant enzymes. However, no damages or biochemical changes were observed in puppies from the rats co-treated with lead and dandelion. These results indicate that supplementation of pregnant and lactating rats with dandelion protects their offspring against lead poisoning, likely through reduction of oxidative stress and liver damages.
... The DNA became fragmentated significantly in the liver of rats exposed to lead [25]. Lead also caused the disturbance in the lipid peroxide oxidation system in the mature liver and inhibition of the aminoacids and other small molecules transformation into glucose, which impaired the normal function of mitochondria [20]. The mitochondrial membranes and cell membranes became more vulnerable [23,25]. ...
... Lead intoxication during pregnancy caused the reduction of liver weight in newborn rats. It also led to the increase of the level of oxidative stress, meanwhile the level of hepatic mRNA, DNA, protein and antioxidant enzyme activities decreased [20]. The lead impact during pregnancy caused the liver dystrophy and decomposition of liver lobules in newborn rats and during the first month after birth, as well as the sinusoidal hypertrophy, edema of interstitial spaces, lymphocyte infiltration of the portal tracts, and the reduction of glycogen in hepatocytes [3,10,25]. ...
... The supplementation of natural products like spirulina or dandelion during pregnancy diminished the signs of oxidative stress, restored the level of hepatic DNA, mRNA and protein, and eliminated the inhibition of the antioxidant enzymes in the liver induced by lead [20,34]. The powder of wine yeast Sassharamyces vini administreted before and during pregnancy showed the significant protective effect for the restoring of the blood cell population in the fetal liver; this result can be explained by its antioxidant effect. ...
Lead is one of the most widespread pollutant which alters the mature liver and is especially harmful for the fetal liver. The typical alterations in the mature liver after the lead exposure are the hypertrophy and vacuolization of hepatocytes, circulatory disorders, mononuclear cellular infiltration. The morphological changes in the liver during prenatal development under the maternal lead treatment are inhibition of hematopoiesis, dystrophy of hepatocytes, disturbances in the liver architecture, its vessels and stroma with a gradient of pathological changes toward the peripheral parts of the organ. The manifestations of liver alteration after birth become deeper with age and develop to the necrosis, edema and inflammation. The biochemical disturbances in the liver are the decrease in the activity of enzyms of energy metabolism, inhibition of protein and nucleic acids synthesis, imbalance of the lipid peroxide oxidation system, and the increasing of oxidative stress with the further alteration of the membranes of the endothelium, red blood cells, hepatocytes, as well as mitochondrial membrane. The changes in expression of the immunohistochemical markers can differentiate the processes in the liver, which are relatively stable or sensitive to lead, especially in prenatal development, whereas the biochemical parameters are valuable for estimation of the liver damage in postnatal life. The immunohistochemical changes under the lead treatment reflect the inhibition in protein synthesis such as albumin and cytokeratins, as well as growth factors, nitric oxide synthases and matrix metalloproteinases expression; whereas the expression of apoptotic markers increases. The search for the natural products, dietary supplements and drugs with the protective properties is ongoing and covers the wide spectrum of agents, including vitamins, micro- and macroelements, antioxidants, chelating agents, natural extracts, proteins, sorbents and complex-producing drugs. The immunohistochemical markers as well as biochemical parameters can be used to prove the efficacy of protectants for chronic lead intoxication.
... Moreover, it was shown that supplementing female rats' diet with up to 2% dandelion extract does not provide a toxic effect, nor does it increase oxidative stress. It was finally assumed that the microsphere extract's antioxidant action from the dandelion root would be responsible for improving the oxidative status during the lead poisoning [67]. ...
... The highlighted therapeutic actions of Taraxacum officinale L. leaves are mainly attributed to their content of natural products such as polyphenols, flavonoids, tannins, and sesquiterpenes. Thus, extracts of dandelion leaves were reported to have hepatoprotective properties in liver cancer [46], lead-poisoning [67], drug-induced hepatic damage [59,65], and non-alcoholic fatty liver disease [68,69]. However, other studies indicate that aqueous extracts of dandelion leaves are also beneficial in managing diabetes by improving carbohydrate metabolism and having α-amylase and α-glucosidase inhibitory activities [51,55]. ...
The current pharmacological agents advised for the management of diabetes as well as cardiovascular and hepatic diseases are subject to numerous studies for safety and efficacy. Therefore, it is worth looking into alternative therapeutic aids such as natural products of medicinal plants. By a broad review of in vitro and in vivo studies on the various dandelion, chicory, and mulberry extracts, this work highlights their bioactive compounds and therapeutic action when used as a prevention and management aid in public health such as diabetes, cardiovascular disease, and hepatic disorders like non-alcoholic steatohepatitis. Natural products of dandelion leaves and root extracts can suppress the development of liver cancer, decrease insulin resistance, and suppress total triglyceride and cholesterol levels. Recent studies on mulberry leaves extracts indicated that they could decrease palmitic acid-induced lipotoxicity, increase total cholesterol and bile acid excretion, improve superoxide dismutase expression, and improve insulin resistance. Chicory root extracts boost satiety, reverse insulin resistance, and augment lipid metabolism thanks to their contents in chicoric acid, chlorogenic acid, and polysaccharides. Taraxacum officinale L., Morus nigra L., and Cichorium intybus L. present hepatoprotective, anti-inflammatory, antioxidant, hypolipidemic, and hypoglycemic activities and are shown to be advantageous in the management of obesity, dyslipidemia, Type 2 diabetes, and non-alcoholic fatty liver diseases. These plants are commonly available in the European spontaneous flora and more attention could be paid to their natural products.
... The beneficial impacts on various cardiovascular parameters in animals fed with a diet enriched with dandelion have also been observed. Firstly, neither a toxic effect nor increased oxidative stress have been revealed by supplementation of the diet of adult female rats with dandelion doses up to 2% [28]. Dandelion alcohol leaf fractions administered to male rats (200-400 mg/kg BW) have been found to possess protective actions against The E max and pD 2 parameters are presented in Table 1. ...
... The beneficial impacts on various cardiovascular parameters in animals fed with a diet enriched with dandelion have also been observed. Firstly, neither a toxic effect nor increased oxidative stress have been revealed by supplementation of the diet of adult female rats with dandelion doses up to 2% [28]. Dandelion alcohol leaf fractions administered to male rats (200-400 mg/kg BW) have been found to possess protective actions against CCl 4 -induced liver tissue toxicity [29]. ...
Alcoholic leaf and petal fractions of Taraxacum officinale (dandelion) were previously demonstrated to exert in vitro antioxidant and antithrombotic activities in blood plasma and platelets. Eight-week-old male Wistar rats (n = 6) were supplemented for four weeks with dandelion fractions (694 mg/kg of diet = 11.9 ± 0.6 mg daily). Dandelion leaf and petal fractions, which delivered daily 4.10 ± 0.05 and 1.41 ± 0.07 mg l-chicoric acid, respectively, were shown to exert antioxidative actions, measured as decreased levels of thiobarbituric acid-reactive substances (TBARS) in the spleen (≈0.8-fold, leaves and petals), brain (0.53-fold, leaves) and thoracic arteries (0.59-fold, petals). Moreover, petal fraction increased thiols in the blood plasma (1.58-fold), while leaf fraction decreased protein carbonylation levels (0.59-fold). Additionally, dandelion leaf fractions modified the lipid profile: decreased triglyceride (0.44-fold), total cholesterol (0.73-fold), lipoprotein combine index (0.32-fold) and the atherogenic index of plasma (0.62-fold). Dandelion fractions showed a beneficial decrease effect in the participation of cyclooxygenase products in the noradrenaline-induced vascular contractions of thoracic arteries. Meanwhile, only the dandelion leaf fraction augmented acetylcholine-induced vasodilation and upregulated KATP channels. The heart rate and blood pressure were not modified. Dandelion leaf and petal phenolic fractions, enriched with l-chicoric acid, are promising plant materials that may exert in vivo beneficial antioxidant effects.
... The pathogenesis of lead toxicity is multifactorial, as lead directly interrupts enzyme activation, competitively inhibits trace mineral absorption, interrupting the structural protein synthesis, as well as, mimics biologically helpful minerals such as calcium, iron and zinc (Ercal et al. 2001). Pb is a nonthreshold multitargeted toxicant that causes alterations in different organs of the body, including nephrotoxicity (Moneim et al. 2011;Mandal et al. 2012), hepatoxicity (Gargouri et al. 2016(Gargouri et al. , 2017, oxidative stress, excitotoxicity and DNA damage (Gargioni et al. 2006;Jurczuk et al. 2007;Yurekli et al. 2009;Dai et al. 2010). In addition, the immunosuppressive effect has been documented with lead toxicity (Ahamed & Siddiqui 2007). ...
... As such, it is one of the major organs involved in the storage, bio-transformation and detoxification of toxic substances (Mudipalli 2007). Previous studies have already reported that the heavy metals cause different damages at the hepatic levels in rats under different experimental conditions (Liu et al. 2015;Gargouri et al. 2017). Plasma enzymes, such as AST and ALT, are an important class of enzymes linking carbohydrate and amino acid metabolisms. ...
Lead (Pb) is a very toxic metal present in the environment, causing disturbances of several functions. Preventive or curative effects of halophytic plants against these disorders may be a promising and safe therapeutic strategy. Thus, this study was designed to evaluate in vivo immunomodulatory and antioxidant effects of Sarcocornia perennis extract (Sp) against lead toxicity in rats. Groups of six animals each were treated with plant extract (via food), 6 g/L lead acetate (via drinking water) or a combination of both. At the end of the 3-week period, rat exposure to lead caused reduction of liver weight but an increase of that of kidney. Moreover, lead intoxication induced oxidative stress manifested by significant increases of inflammatory cytokines (except IL-10) and lipid peroxidation (TBARS), compared with the control group. Meanwhile, interleukin 10 and glutathione levels (GSH), as well as antioxidant activities of superoxide dismutase (SOD), Catalase (CAT) and glutathione-peroxidase (GPx), were decreased. Considering liver and renal markers, lead treatment induced a significant increase in the activities of aminotransferases (AST, ALT), and in the levels of urea, creatinine and phosphorous, whereas total plasma protein, albumin and calcium levels were significantly decreased. S. perennis extract alone did not induce any significant changes in hepatic or renal markers, whereas the antioxidant markers were significantly increased.
S. perennis supplementation significantly reduced the lead-induced elevation of serum IL-1ß, IL-6, TNF-α, IFN-γ and TBARS, but increased the IL-10 and antioxidant enzyme activities. Overall, plant components ameliorated hepatorenal damages caused by lead.
... Plasma samples were mmol.L −1 of NaCl using an ultra-Turrax device. The homogenates were centrifuged at 5000g for 25 minutes at 4 C and aliquots of supernatant were kept at −20 C until analyses and for RNA extraction.In parallel, portions of liver were immediately fixed into Bouin solution (saturated picric acid added with 37-40% formaldehyde and glacial acetic acid, 75:25:5 v/v) for histological studies.30 2.5 | Serum parametersSerum samples were obtained by the centrifugation of blood at 2700g for 15 minutes at 4 C and were then divided into Eppendorf tubes. ...
The present study aimed (1) to investigate the chemical composition as well as the anti‐inflammatory properties and in vitro antioxidant activity of Citrus aurantium peel essential oil (p EOCa ) and (2) to evaluate its potential effect in vivo. The main results showed that the major components of p EOCa are Limonene and Linalool. Additionally, DPPH scavenging ability and β‐carotene bleaching inhibition tests confirmed the antioxidant capacity of p EOCa . Our oil reduced the production of NO by LPS‐stimulated RAW264,7 macrophages in a concentration‐dependent. This inhibition occurred at a transcriptional level. p EOCa in CCl4 treated rats alleviated hepatotoxicity as monitored by the improvement of hepatic oxidative stress biomarkers levels plasma biochemical parameters, and DNA molecule aspect. Furthermore, the mRNA gene expression of Cu‐Zn SOD, CAT, and GPx increased under CCl4+ p EOCa exposure to reach the same value to the control. Similarly, antioxidant activities of these three enzymes changed in accordance with the mRNA levels. These results were confirmed by the histological results. It seems obvious that the treatment with p EOCa prevented liver damage induced by CCl4, thus preventing the harmful effects of free radicals.
... A number of pharmacological activities have been attributed to this plant such as anti-inflammatory, anti-proliferative, and anti-oxidant effects [8]. It has been reported that T. officinale extract protects against lead-induced brain damage [9]. It has been also shown to exhibit hepatoprotective effects [10]. ...
Background
Depression is a common disorder linked with high levels of chronicity, psycho-social and physical problems, and suicide. Here, we assessed the antidepressant effects of the hydromethanolic extract of Taraxacum officinale and investigated the underlying mechanism.
Material/Methods
Antidepressant effects were examined by use of the tail suspension test (TST). Concentrations of corticosterone, dopamine, noradrenaline, and adrenaline were examined by biochemical assays. The mRNA expression was assessed by quantitative RT-PCR. Phytochemical analysis was performed by LC/MS.
Results
The results showed that the extract at the dosage of 50 and 100 mg/kg significantly (p<0.01) alleviated the TST-induced immobility in the mice, and the effects were comparable to the antidepressant drug Bupropion, which was used as the positive control. Investigation of the underlying mechanism revealed that the T. officinale extract exerts it effects by significantly (p<0.05) decreasing the levels of corticosterone and increasing the concentrations of dopamine, noradrenaline, and adrenaline. Further, the extract also increased the expression of brain-derived neurotrophic factor (Bdnf), which was associated with significant (p<0.05) decrease in the expression of mitogen-activated protein kinase phosphatase-1 (Mkp-1), indicative of the antidepressant potential of T. officinale. Finally, the active constituents of the extract, which include isoetin, hesperidin, naringenin, Kaempferol, sinapinic, and gallic acid, were also identified, which could potentially be responsible for its antidepressant effects.
Conclusions
In conclusion, T. officinale exerts significant antidepressant effects in a mouse model of depression by inhibition of corticosterone levels and modulation of Mkp-1 and Bdnf expression.
... Plasma samples were mmol.L −1 of NaCl using an ultra-Turrax device. The homogenates were centrifuged at 5000g for 25 minutes at 4 C and aliquots of supernatant were kept at −20 C until analyses and for RNA extraction.In parallel, portions of liver were immediately fixed into Bouin solution (saturated picric acid added with 37-40% formaldehyde and glacial acetic acid, 75:25:5 v/v) for histological studies.30 2.5 | Serum parametersSerum samples were obtained by the centrifugation of blood at 2700g for 15 minutes at 4 C and were then divided into Eppendorf tubes. ...
... 28 Several bibliographic data has demonstrated that Pb is a chemical widely used for induction of liver damage in experimental animals. 14,29 Susceptibility of the liver to injury can trigger and eventually lead to various liver diseases and is attributed to the ROS and free radicals generated during its metabolism. 30,31 In this study, lead injected during 10 days had no effect on body and liver weights and OSI thus suggesting that the general metabolic Values are expressed as means AE SD of 6 animals in each group. ...
Environmental pollutants, particularly lead, pose a serious threat to human and animal health that causes disturbances of several functions, including hepatotoxicity. Therefore, the search for a new treatment that could safely and effectively block or reverse liver injuries remains a challenge. This study was carried out to investigate the protective efficacy of Juglans regia vegetable oil (JRVO) against the hepatotoxicity induced by lead. To achieve this aim, adults male rats were treated for 10 days with Pb (0.344 g/kg bw) associated or not with JRVO (0.9 g/kg bw). The rats intoxicated by lead exhibited oxidative stress determined by TBARS, protein carbonyls, liver tumor necrosis factor‐α (TNF‐α), caspase‐3, and antioxidant status: SOD, CAT, GPx, and GSH. Administration of lead increased the levels of plasma hepatic markers (AST, ALT, LDH) and bilirubin, the lipid profiles (total cholesterol, triglycerides, VLDL‐Ch, LDL‐Ch levels, TBARS, NOx, and PCO), the plasmatic lipase activity and the inflammatory markers, while the plasmatic ALP decreased. Coadministration of JRVO restored all the hepatic markers, the lipid profiles and the antioxidants to near‐normal values and lowered the plasmatic lipase activity as well as the elevated thiobarbituric acid reactive substances. Hepatic histological studies confirmed the beneficial role of JRVO through the amelioration of all biochemical parameters. Our results suggest that Juglans regia vegetable oil contains promising substances to counteract the lead intoxication and may be efficient in the prevention of hepatotoxicity complications.
... After one week of acclimatization, the animals were randomly divided into three groups of six rats as follows: • Group One (Controls): rats received distilled water injected intarperitoneally 1 mL of saline solution (0.9 %). • Group Two (Pb): rats received distilled water injected daily with lead (0.344 g/kg body weighs) (Gargouri et al., 2016). • Group Three (Pb+J): rats received oral gavage with JRVO (0.9 g/kg body weight) associated with lead (0.344 g/kg body weighs) injected intraperitoneally. ...
Lead (Pb) intoxication remains a major health hazard causing various deleterious effects especially on renal and hematologic system. The current study elucidated the potential protective effect of JRVO against nephrotoxicity induced by lead. Male rats were randomly divided into three groups: group one (control) received ad libitum distilled water and 1 mL of saline solution (0.9 %) given by intra-peritoneal (i.p) injection, group two (Pb) was kept on tap distilled water and animals were i.p, injected daily with lead every two days from day five until day ten, namely the sacrifice day, and group three (Pb+J) was administered by intra-peritoneal injection of Pb with the same dose and same way with Group two, while JRVO extract was administered daily by gavage during ten days. The exposure of lead reduced the number of red and white blood cells. Besides, plasma biomarkers (urea, uric acid, creatinine, LDH and ALP) levels were reduced. Lipid and protein per-oxidations increased and objectified by high TBARS and PCOs levels, while glutathione peroxidase, superoxide dismutase and catalase activities showed a significant decline after ten-day treatment. Conversely, the JRVO prevented kidney biomarker changes by improving hepatotoxicity induced by lead as evidenced by restoring the biochemical markers cited above to near normal levels. Kidney histoarchitecture confirmed the biochemical parameters and the beneficial role of JRVO. It can be concluded that the administration of JRVO alleviates Pb-induced toxicity, thus demonstrating its potent antioxidant efficacy.
... [25] Dandelion has been widely used as a traditional medicine against various disorders. [26,27] It has been found the phenolic compounds in dandelion including: luteolin, chrysoeriol, chicoric acid, and chlorogenic acid. [6] Among them, luteolin and chicoric acid are the most abundant phenolic compounds. ...
Background: Dandelion is commonly used in traditional Chinese medicine with several active compounds found in extracts. It has a variety of pharmacological effects, such as a reduction in swelling and inflammation, and detoxification. The mechanism by which dandelion extract inhibits the inflammatory response in skeletal muscle cells remains unknown; therefore, the aim of this study was to investigate the effects of dandelion extract root on the proliferation of skeletal muscle cells and the alleviation of lipopolysaccharide (LPS)-induced inflammatory response in vitro.
Methods: Rat skeletal muscle cells were isolated from Sprague-Dawley rat and cultured in vitro which were cultured in basal medium, or medium containing LPS or dandelion extract. Cell counting kit-8 (CCK-8) was employed to measure cell proliferation; meanwhile, the optimal concentration of dandelion extract and treatment time were selected. Crystal violet staining was used to detect the proliferation of muscle cells. Western blotting analysis was used to detect the levels of inflammatory factors, myogenic factor, and p-AKT protein expression.
Results: The optimal concentration and treatment time of dandelion extract for the following study were 5 mg/ml and 4 days, respectively. Dandelion extract was found to increase proliferation of rat skeletal muscle cells (t = 3.145, P < 0.05), with the highest effect observed at 5 mg/ml. LPS was found to decrease proliferation of skeletal muscle cells (t = −131.959, P < 0.001), and dandelion extract could against this affection (t = 19.466, P < 0.01). LPS could induce expression of inflammatory factors, including interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α (IL-1β: t = 9.118, P < 0.01; IL-6: t = 4.346, P < 0.05; TNF-α: t = 15.806, P < 0.05), and dandelion extract was shown to reduce LPS-induced expression of IL-1β, IL-6 and TNF-α (IL-1β: t = −2.823, P < 0.05; IL-6: t = −3.348, P < 0.01; and TNF-α: t = −3.710, P < 0.01). Furthermore, LPS was also shown to decrease expression of myogenic factor, including myod1 and myogenin (MyoD1: t = 4.039, P < 0.05 and myogenin: t = 3.300, P < 0.01), but dandelion extract was shown to against this effect of LPS (MyoD1: t = −3.160, P < 0.05 and myogenin: t = −3.207, P < 0.01). And then, LPS was found to increase expression of p-AKT protein (p-AKT/AKT: t = 4.432, P < 0.05). Moreover, expression of p-AKT protein was found to decrease, with 5 mg/ml of dandelion extract (p-AKT/AKT: t = −3.618, P < 0.05).
Conclusions: The findings indicate that dandelion extract plays an important role in skeletal muscle cells viability regulation, promote cells proliferation by increasing level of p-AKT protein expression, and reduce LPS-induced expression of inflammatory factors, inhibiting the inflammatory response of rat skeletal muscle cells.
... Group I (C): normal control group, treated intraperitoneally (i.p.) with isotonic saline (0.9%). Group II (Pb): Pb toxin group, treated by intraperitoneal injection (343.6 mg Pb/kg body weight (bw) dissolved in 0.2 ml isotonic saline) (Gargouri et al., 2016). Group III (Pb þ Zn): received Pb (343.6 mg Pb/ kg bw) by the same route as group II and 10 mg/kg bw of Zn by intraperitoneal injection (Alam and Kelleher, 2012). ...
Lead (Pb) is a toxic metal that induces a wide range of biochemical and physiological effects in humans. Oxidative damage has been proposed as a possible mechanism involved in Pb toxicity. The current study was carried out to evaluate the antioxidant activities of zinc (Zn) supplement against lead acetate–induced kidney injury in rats. In this study, adults male rats were treated for 15 days with Pb (0.344 g/kg body weight (bw)) associated or not with Zn (10 mg/kg bw). Our study showed that supplementation with Zn prevented renal dysfunction as indicated by plasma biomarkers (urea, uric acid, creatinine, lactate dehydrogenase, and alkaline phosphatase levels) and oxidative stress–related parameters (thiobarbituric acid reactive substances, protein carbonyl, advanced oxidation protein product, superoxide dismutase, catalase, glutathione peroxidase, and vitamins (A, E)) in kidney tissue. The corrective effect of Zn on Pb-induced kidney nephrotoxicity recovered normal kidney histology. Overall, this study indicates that Zn alleviated the toxic effects of this heavy metal on renal tissue, suggesting its role as a potential antioxidant and nephroprotective agent.
... AST is amply expressed in the brain, skeletal muscle, kidney, and heart [53]. Viral hepatitis, alcohol abuse, exposure to lead, mercury, organophosphorus compounds, medicines (acetaminophen, statins, HIV medications) have shown increase ALT and AST levels [54][55][56]. Bilirubin, a breakdown product of heme catabolism is elevated by infections, biliary obstruc- tion, metabolic disorders and exposure to drugs/toxins [55,57]. Re- markably, our results show that ALT, AST and bilirubin were sig- nificantly increased due to the exposure to Corexit alone or to DWH oil, suggesting that exposure to these contaminants can significantly in- crease the risk for hepatocellular damage and result in biochemical impairment and lesions in the tissue and cellular functions. ...
The 2010 Deepwater Horizon (DWH) oil spill is the largest marine oil spill in US history. In the aftermath of the spill, the response efforts used a chemical dispersant, Corexit, to disperse the oil spill. The health impacts of crude oil and Corexit mixture to humans, mammals, fishes, and birds are mostly unknown. The purpose of this study is to investigate the in vivo effects of DWH oil, Corexit, and oil-Corexit mixture on the general behavior, hematological markers, and liver and kidney functions of rodents. C57 Bl6 mice were treated with DWH oil (80 mg/kg) and/or Corexit (95 mg/kg), and several hematological markers, lipid profile, liver and kidney functions were monitored. The results show that both DWH oil and Corexit altered the white blood cells and platelet counts. Moreover, they also impacted the lipid profile and induced toxic effects on the liver and kidney functions. The impacts were more pronounced when the mice were treated with a mixture of DWH-oil and Corexit. This study provides preliminary data to elucidate the potential toxicological effects of DWH oil, Corexit, and their mixtures on mammalian health. Residues from the DWH spill continue to remain trapped along various Gulf Coast beaches and therefore further studies are needed to fully understand their long-term impacts on coastal ecosystems.
As a well-recognized dietary and medicinal plant, Taraxacum mongolicum Hand.-Mazz (TMHM) has been used for making wines, candies, energy drinks, and other functional foods. The TMHM contains a diverse range of active phytoconstituents, including flavonoids, triterpenoids, phenolic acids, sesquiterpene lactones, pigments, coumarins and sterols. Recent pharmacological evidence has revealed multiple biological effects of TMHM, including anti-inflammatory, antioxidant, antibacterial, and gastric-protective effects, which contribute to the ameliorative effects of TMHM on inflammation-associated diseases, constipation, gastric disorders, empyrosis, hyperlipidemia, and swollen carbuncles. Although recent advances have highlighted the potential of TMHM to be applied in the clinical practice, food, and nutraceutical industry, the mechanistic understanding and systematic information on TMHM are still scarce. Here, in this timeline review, we have attempted to compile literary documents on pharmacological potential of TMHM concerning its chemical composition, biological activities, toxicity, and pharmacokinetics to promote further researches on clinical and therapeutic potential of TMHM and its food/nutraceutical applications.
Taraxacum syriacum (TS) with natural antioxidant and pharmacological activities may be considered for treatment of oxidative stress induced by acetaminophen (APAP). The aim of the present study was to evaluate the ameliorative effects of the ethanol extract of TS root against hepatorenal toxicity induced by APAP in comparison to N-acetylcysteine (NAC) as a standard drug. Thirty male Wistar rat were randomly divided into five groups. Control group; APAP (1g/kg) group; APAP-NAC (160 mg/kg) group and APAP-TS100 and APAP-TS200 groups: APAP plus 100 and 200 mg/kg of TS extract, respectively. After 7 days treatment, serum and liver and kidney tissues were prepared and evaluated. TS extract ameliorated the increased lipid peroxidation level and decreased antioxidant enzymes activities and glutathione level in liver and kidney of APAP-treated rats. Moreover, treatment with the TS extract caused significant reduction in the histopathological damages and high levels of serum biochemical markers of hepatic and renal functions after APAP treatment. This study suggests that the extract of TS roots has dose-dependent ameliorative effect against APAP-induced oxidative damage in liver and kidney due to its free radical scavenging and antioxidant properties. The overall efficacy of the extract at 200 mg/kg dose is comparable with NAC.
Evidence has accumulated that exposure to widespread environmental toxicants, such as heavy metals, persistent organic pollutants, and tobacco smoke adversely affect fetal development and organ maturation, even after birth. The developing immune and respiratory systems are more sensitive to environmental toxicants due to their long-term physical development, starting from the early embryonic stage and persisting into early postnatal life, which requires complex signaling pathways that control proliferation and differentiation of highly heterogeneous cell types. In this review, we summarize the effect of early-life exposure to several widespread environmental toxicants on immune and lung development before and after birth, including the effects on immune cell counts, baseline characteristics of cell-mediated and humoral immunity, and alteration of lung structure and function in offspring. We also review evidence supporting the association between early-life exposure to environmental toxicants and risk for immune-related diseases and lung dysfunction in offspring in later life.
Lead is the major environmental toxin resulting in the ill health and deleterious effect on almost all organs in the human body in a slow and effective manner. The best treatment for lead poisoning is chelation therapy which is next only to prevention. The authors describe the disruption of homeostasis of the human body by lead in various tissues like blood, bones, liver, kidneys and brain; and the ability of lead to enter the cell using calcium channels and calcium receptors like Ca++ dependant K+ ion channels, transient receptor potential channels, T-tubules, calmodulin receptors, inositol trisphosphate receptors and ryanodine receptors. We report a few novel chelating agents like ionophores, decadentate ligands, picolinate ligands, octadentate ligand, allicin, thiamine, that show good potential for being used in chelation therapy. Future of lead poisoning is a challenge to all and it needs to be meticulously studies to have an economic and health approach.
Lead (Pb) is a highly toxic heavy metal for both plants and animals; the environment is increasingly polluted with heavy metals and reduces crop productivity. Plants possess homeostatic mechanisms that allow them to keep correct concentrations of essential metal ions in cellular compartments and to minimize the damaging effects of an excess of nonessential ones. One of their adverse effects on plants are the generation of harmful active oxygen species, leading to oxidative stress and the antioxidative activity seems to be of fundamental importance for adaptive response of plant against environmental stress. The present study explores the effects of lead (soil treated twice/ week) with (10, 30 and 60 mM) on the specific activities of phosphatases which might lead to reducing power assay in (Triticum aestivum PBW344) seedling. A significant decrease in the redox potential of shoot compared to root was observed at the similar concentration of lead. A similar trend on leaves was also noted. Acid and alkaline phosphatase activities were significantly higher in roots than in shoot at all the three concentration of lead i.e. 10, 30 and 60 mM, compared to controls. The above mentioned changes were more pronounced at 60 mM concentration of lead than two other concentrations. These results lead us to suggest that increased lead concentration in soil might lead to adverse effects on plant growth and phosphatase activities.
Adult males of the Wistar albino rats (Rattus norvegicus) were exposed to lead acetate trihydrate in drinking water (0.0%, 0.25%, 0.5%, 1% and 2% for 1-12 months) to investigate histological and histochemical alterations induced by lead intoxication in the liver. Chronic exposure to subtoxic concentrations of lead produced changes in the hepatocytes, portal triads and the sinusoids. The alterations in the hepatocytes were mainly anisokaryosis, nuclear vesiculation, binucleation, cytoplasmic inclusions, cytoplasmic swelling, hydropic degeneration, necrosis and reduction in glycogen content. In addition, portal triads mild chronic inflammation, Kupffer cells hyperplasia and occasional fatty change were seen together with hemosiderosis. No portal fibrosis or cirrhosis was detected due to chronic subtoxic doses of lead exposure in the liver of any member of the dose groups over the entire period of the study. Chronic lead exposure also increased the activities of alkaline phosphatase and α-glycerophosphate-dehydrogenase which might be an adaptation to the metabolic, structural and functional changes in the organelles of hepatic cells due to lead intoxication. The findings revealed that chronic exposure to lead produced significant histological and histochemical changes in the liver of the Wistar albino rats.
This study aimed to investigate the protective effect of dandelion water extract (DWE) on liver injury induced by D-galactosamine (GalN) in Sprague-Dawley rats. Fifty rats were divided into 5 groups; normal control (C), DWE-control (DWE-C: saline injection after feeding 3% DWE diet), GalN-control (GalN-C: GalN injection after normal diet), DWE I (GalN injection after feeding 1.5% DWE diet), and DWE II (GalN injection after feeding 3% DWE diet). After 2 weeks, the acute hepatitis was induced by GalN (650 mg/kg, i.p.) and 24 hrs later, all rats were sacrificed. The DWE supplement ameliorated the serum alanine and aspartate aminotransferase (AST, ALT) as well as alkaline phosphatase (ALP) and tumor necrosis . Hepatic antioxidative enzyme activities, such as catalase, GSH peroxidase, GSH reductase, and Mn-superoxide dismutase (SOD) were slightly or significantly elevated by the treatment of DWE. Moreover, the histological examination corresponded with these biochemical observations. According to these findings, dandelion could be used as a potential therapeutic material for treating chemically induced acute hepatitis.
This study deals with the impact of chronic exposure to lead on male and female fertility in rats. Male and female rats (3 months old) were fed on commercial tablets (SICO, Sfax). For drinking, some rats were given distilled water (T = controls), the other ones were given distilled water enriched with lead acetate, either 3 (P1 group) or 6 mg ml–1 (P2 group), for 15, 30, 45, 60 or 90 days. In male rats, absolute and relative weights of testis, epididym, prostate and seminal vesicles were found to significantly decrease at day 15 in the P2 group and at day 45 in the P1 group. However, at day 60, these absolute and relative weights returned to control values. Lead-induced pathological changes in spermatogenesis were observed at day 15 by histological study: arrest of cell germ maturation, changes in the Sertoli cells, and presence of apoptotic cells revealed by borated toluidine blue in the testis. Presence of lead deposits was observed after histochemical staining using sodium rhodizonate. Serum testosterone level was found to be lowered at day 15 in both (P1) and (P2) groups, to display a peak at day 60, then to return to controls values, in spite of the continuation of the treatment. In female rats, absolute and relative weights of ovary and uterus were found unchanged. The vaginal smears practised in females revealed the oestrus phase in all groups. Exposed females were mated with control males, and fecundity was assessed 15 days later by counting the number of pregnancies and the number of conspectuses per pregnancy. Fertility was found to be reduced in females of P1 and P2 groups as compared to control females (T group). Lead level in blood was found to be poorly correlated with the level of poisoning, whereas lead accumulation in tail was found to be dose-dependent. Therefore, lead accumulation in tail appears as a more reliable biomarker of exposure to lead. In summary, our study shows that chronic exposure to lead causes a double sexual disorder in rats: first, disorder deals with the hormonal function, which is affected at the early stages of poisoning, but is rapidly corrected; second, disorder deals with the genital tract, affecting the testis and the ovary, resulting in a reduced fertility in both P1 and P2 females, in spite of the presence of a normal oestrus. The cytotoxic effect of lead in males seems to be related to an apoptotic process.
Amino acid transfer to the fetus is dependent on several different factors. While these factors can be understood in isolation, it is still not possible to predict the function of the system as a whole. In order to do this an integrated approach is required which incorporates the interactions between the different determinants of amino acid transfer. Computational modelling of amino acid transfer in the term human placenta provides a mechanism by which this integrated approach can be delivered. Such a model would be invaluable for understanding amino acid transfer in both normal and pathological pregnancies. In order to develop a computational model it is necessary to determine all the biological factors which are important contributors to net amino acid transfer and the ways in which they interact. For instance, how different classes of amino acid transporter must interact to transfer amino acids across the placenta. Mathematically, the kinetics of each type of transporter can be represented by separate equations that describe their transfer rate as a non-linear function of amino acid concentrations. These equations can then be combined in the model to predict the overall system behaviour. Testing these predictions experimentally will demonstrate the strengths and weaknesses of the model, which can then be refined with increasing complexity and retested in an iterative fashion. In this way we hope to develop a functional computational model which will allow exploration of the factors that determine amino acid transfer across the placenta. This model may also allow the development of strategies to optimise placental transfer in pathologies associated with impaired amino acid transfer such as fetal growth restriction.
Bank voles free living in a contaminated environment are known to be more sensitive to cadmium (Cd) toxicity than the rodents exposed to Cd under laboratory conditions, but the reasons for this difference are poorly defined. The present work was designed to determine whether dietary lead (Pb), a common environmental co-contaminant, and/or animal density that affects various physiological processes, would influence susceptibility to Cd toxicity in the kidneys and liver of these animals. For 6 weeks, the female bank voles were kept individually or in a group of six and provided with diet containing environmentally relevant concentrations of Cd [<0.1 μg/g (control) and 60 μg/g dry wt] and Pb [<0.2 μg/g (control) and 300 μg/g dry wt] alone or in combination. At the end of exposure period, histopathology and analyses of metallothionein, glutathione and zinc that are linked to a protective effect against Cd toxicity, as well as Cd, Pb, copper, iron and lipid peroxidation were carried out. Histopathological changes in the kidneys (a focal glomerular swelling and proximal tubule degeneration) and liver (a focal hepatocyte swelling, vacuolation and inflammation) occurred exclusively in some bank voles kept in a group and exposed to Cd alone (2/6) or Cd + Pb (4/6). The observed toxicity in grouped bank voles appeared not to be based on altered (1) tissue disposition of Cd and/or Pb, (2) metallothionein, glutathione and zinc concentrations, or (3) tissue copper, iron and lipid peroxidation. The data indicate that high population density in combination with environmental Pb may be responsible for an increased susceptibility to Cd toxicity observed in bank voles free living in a contaminated environment; the mechanism by which animal density affects Cd toxicity deserves further study.
Oxidative damage has been proposed as a possible mechanism involved in lead toxicity, specially affecting the liver and kidney. Previous studies have shown the antioxidant effect of Spirulina maxima in several experimental models of oxidative stress. The current study was carried out to evaluate the antioxidant activity of Spirulina maxima against lead acetate-induced hyperlipidemia and oxidative damage in the liver and kidney of male rats. Control animals were fed on a standard diet and did not receive lead acetate (Control group). Experimental animals were fed on a standard laboratory diet with or without Spirulina maxima 5% in the standard laboratory diet and treated with three doses of lead acetate (25 mg each/weekly, intraperitoneal injection) (lead acetate with Spirulina, and lead acetate without Spirulina groups).
The results showed that Spirulina maxima prevented the lead acetate-induced significant changes on plasma and liver lipid levels and on the antioxidant status of the liver and kidney. On the other hand, Spirulina maxima succeeded to improve the biochemical parameters of the liver and kidney towards the normal values of the Control group.
It was concluded that Spirulina maxima has protective effects on lead acetate-induced damage, and that the effects are associated with the antioxidant effect of Spirulina.
The protective effects of Taraxacum officinale (dandelion) root against alcoholic liver damage were investigated in HepG2/2E1 cells and ICR mice. When an increase in the production of reactive oxygen species was induced by 300 mM ethanol in vitro, cell viability was drastically decreased by 39%. However, in the presence of hot water extract (TOH) from T. officinale root, no hepatocytic damage was observed in the cells treated with ethanol, while ethanol-extract (TOE) did not show potent hepatoprotective activity. Mice, which received TOH (1 g/kg bw/day) with ethanol revealed complete prevention of alcohol-induced hepatotoxicity as evidenced by the significant reductions of serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase activities compared to ethanol-alone administered mice. When compared to the ethanol-alone treated group, the mice receiving ethanol plus TOH exhibited significant increases in hepatic antioxidant activities, including catalase, glutathione-S-transferase, glutathione peroxidase, glutathione reductase, and glutathione. Furthermore, the amelioration of malondialdehyde levels indicated TOH's protective effects against liver damage mediated by alcohol in vivo. These results suggest that the aqueous extract of T. officinale root has protective action against alcohol-induced toxicity in the liver by elevating antioxidative potentials and decreasing lipid peroxidation.
Oxidative stress plays a key role in lead (Pb)-induced nephrotoxicity. N-acetylcysteine (NAC) is a potent oxygen free radicals scavenger and a metal chelator. In the present study, female Sprague-Dawley rats received PbAc(2) (300 mg/L, via drinking water) and/or NAC (100 mg/kg/day, by intraperitoneal injection) to investigate the protective effect of NAC on Pb-induced renal damage and oxidative stress as well as its mechanism of action. Renal toxicity was evaluated by measuring urinary excretion of total protein, beta(2)-microglobulin, albumin and urinary enzyme markers of tubular necrosis, as well as serum urea nitrogen level. Activities of antioxidant enzymes, contents of glutathione and malondialdehyde in kidney were also measured. Renal cell damage was assessed by electron microscopy. Animals that received both Pb and NAC showed a better renal function than those receiving Pb alone. Lead-induced tubular lesions and mitochondrial damage were markedly reduced in rats that also received NAC. Also, NAC significantly reduced the levels of lipid peroxidation and markedly restored the enzymic and non-enzymatic antioxidants levels in kidney of Pb-treated rats. Moreover, NAC administration significantly increased urinary Pb excretion and decreased its level in the serum and kidney. In conclusion, NAC treatment prevents renal tubular damage induced by chronic Pb administration, most probably through its antioxidant properties and chelating ability.
To evaluate the combined effects of repeated, closely spaced reproductive cycles and dietary intake on maternal nutritional status, lactational performance and litter growth, rats were fed ad libitum or 75 or 60% of ad libitum intake. Dietary treatment began 28 d before breeding and continued until d 14 of the first (L1) or second (L2) lactation. Body weight and carcass fat concentration of dams and their litters were affected in the 75% group; milk yield, milk protein and lactose concentrations and energy content were affected only in the 60% group. Dams and their litters were heavier, had more total carcass protein and higher plasma albumin values in L2 than L1. There was no effect of reproductive period on milk yield or composition. These results indicate that repeated reproductive cycles did not compromise maternal nutritional status, lactational performance or litter growth. Improved outcomes in L2 among the restricted rats appeared to result from gains during the interval between reproductive periods and early in the second pregnancy.
1 Twenty three adults ingested 203Pb as lead acetate on the 12th hour of a 19 h fast. Retention measured 7 days later in a whole-body counter was 61% and whole-body turnover rates suggested that initial uptake had been considerably greater.
2 Balanced meals eaten with 203Pb reduced lead uptake to 4% and the influence of the food lasted for up to 3 h. The effects of phytate, ethylenediaminetetra acetate (EDTA), caffeine, alcohol, glucose, a liquid meal and a light snack were tested separately with intermediate results.
3 The effect of a meal was probably largely due to its content of calcium and phosphate salts but lead uptake was probably further reduced by phytate which is plentiful in whole cereals and it was probably increased by a factor in milk. Uptake with skimmed milk was the same as with whole milk and we suggested that the factor was not fat. Comestibles with low mineral and phytate contents reduced lead uptake by intermediate amounts, possibly by stimulation of digestive secretions.
4 The avid uptake of lead during a fast, the large reduction of lead uptake with meals and the likelihood of variations in gastric-emptying rates and dietary habits may be major causes of variation in body burdens of lead in the population.
Previous rat studies with lead (Pb) have shown that exposure throughout the full gestational period results in persistent immunotoxicity detectable in both juvenile and adult offspring. Gender differences are also evident. However, little is known about the persistent immunotoxic effects of Pb when administered during specific stages of embryonic development. Adult Sprague-Dawley female rats were administered Pb acetate (or control acetate) in their drinking water early in gestation (days 3-9) or late in gestation (days 15-21). Significantly depressed delayed type hypersensitivity (DTH) responses as well as elevated IL-10 production, relative monocyte numbers, and increased relative thymic weights were observed in late-gestation Pb-exposed female offspring assessed as adults. In contrast, late-gestation Pb-treated male offspring had significantly increased IL-12 production and decreased IL-10 production, while the DTH response, relative monocyte numbers and thymic weights were unchanged. With early exposure, the primary alteration was decreased nitric oxide production in Pb-treated males, whereas in Pb-treated females nitrite production was unaltered. These results suggest that at the Pb dosage employed, the embryo may be more sensitive to the full range of Pb-induced immunotoxic effects with late gestational Pb exposure, and the effects of Pb on DTH function are more pronounced in females. The data also indicate that adherent splenocytes (probably macrophages) and T lymphocytes are the primary immune cells affected during fetal Pb exposure, and that gender may influence the impact of Pb exposure on these cells. Therefore, additional developmental immunotoxicity studies are needed to examine critical windows of immune development for immunotoxicity and differential susceptibility based on gender.
Lead is a toxic metal that induces a wide range of biochemical and physiological effects. The present investigation was designed at evaluating the toxic effects of a prenatal exposure to lead of mothers on hepatic tissue of newborn rats, and potent protective effects of spirulina. Female rats were randomly divided into 4 groups which were given a normal diet (control),a diet enriched with spirulina (S), lead acetate administered through drinking water (Pb), or a diet enriched with spirulina and lead contaminated water (S Pb), respectively. The duration of treatments was from the 5th day of gestation to 14 days postpartum. Lead toxicity was assessed by measuring body and liver weights, blood and stomach lead levels, hepatic DNA, RNA and protein amounts, blood enzyme activities (AST and ALT), as well as lipid peroxidation level and activities of antioxidant enzymes in hepatic tissues of neonates. Lead intoxication of mothers caused reduction of liver weight as well as of hepatic DNA, mRNA and protein levels in newborns. Moreover, oxidative stress and changes in antioxidant enzyme activities were recorded. Conversely, supplementation of mothers with spirulina mitigated these effects induced by lead. These results substantiated the potential hepatoprotective and antioxidant activity of spirulina.
Dandelion is a quite widespread medicinal plant, which is widely used as soup, salad, coffee substitute, wine and natural source of flavouring. Its choleretic, diuretic, anti-inflammatory, appetite-stimulating and laxative properties are well known. The aim of this study was to verify the antioxidant properties of lyophilized extracts derived from dandelion root and leaves. The total polyphenol, flavonoid and free SH-group contents of root and leaf extracts were determined spectrophotometrically as well as the hydrogen donating ability and reducing power property. Radical scavenging capacity of extracts was measured in H2O2/·OH-luminol-microperoxidase system by chemiluminometric method. The folium extract with approximately 3 times higher polyphenol (9.9 g%) and 6 times higher flavonoid content (0.086 g%) proved to be more effective as hydrogen-donor (I50=160 μg), reducing agent (740 ASE mg-1) and H2O2 scavenger (I50=155 μg) compared to radix extract with lower polyphenol and flavonoid content.
This study was aimed at evaluating the toxic effects of a prenatal exposure to lead acetate on brain tissues of newborn rats, and potent protective effects of spirulina (Arthropira platensis) or dandelion (Taraxacum officinalis) added to rat diet. Female rats were given a normal diet (control) or a diet enriched with spirulina or dandelion. Additionally, lead acetate was administered to one half of these rats through drinking water from the 5th day of gestation, to day 14 postpartum. Lead toxicity was assessed by measuring blood lead levels, brain weight, tissue damage, as well as protein content, lipid peroxidation and activities of antioxidant enzymes in brain tissues of neonates. Lead poisoning of mothers caused lead deposition in the brain and cerebellum of newborns and cerebellum tissue damages. Moreover, a significant decrease in weight and protein content of these tissues was found. Oxidative stress and changes in antioxidant enzyme activities in brain tissues were also recorded. Conversely, no such damages or biochemical changes were found in neonates from plant fed lead-poisoned mothers. These results strongly suggest that beneficial effects of spirulina- or dandelion-added diet on lead-intoxicated rats proceeded through the reduction of the lead-induced oxidative stress and related damages.
Most assays for superoxide dismutase depend upon competition between the enzyme and some indicating scavenger for O2−. We have investigated the effects of experimental variables on assays based upon the use of either ferricytochrome c or nitro blue tetrazolium. Our results should help investigators to avoid the numerous potential pitfalls which necessarily surround these assay methods.
Quercetin, a flavonoid, effectively improved the lead-induced histology changes including structure damage and leukocyte infiltration in rat liver. The present study was designed to explore the protective mechanism of quercetin against lead-induced hepatic injury. We found that quercetin markedly decreased the MDA and H(2)O(2) levels and lowered the GSH/GSSG ratio in the liver of lead-treated rat. Moreover, quercetin markedly restored Cu/Zn-SOD, Mn-SOD, CAT and GPx activities and upregulated mRNA expression levels of these proteins in the liver of lead-treated rat. Western blot analysis showed that quercetin significantly inhibited apoptosis by modulating the ratio of Bax to Bcl-2 expression and suppressing the expression of phosphorylated JNK1/2 and cleaved caspase-3 in the liver of lead-treated rat. In conclusion, these data suggest that quercetin protects the rat liver from lead-induced injury by attenuating lipid peroxidation, renewing the activities of antioxidant enzymes and inhibiting apoptosis.
The concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), dioxin-like polychlorinated biphenyls (dl-PCBs) and polybrominated diphenylethers (PBDEs) in 33 breast milk samples collected in 2006-2007 from primipara mothers close to four industrial areas of Slovak Republic were determined. The total PCDDs/PCDFs and dl-PCBs expressed as TEQ based on WHO TEFs 1998 in breast milk samples varied from 5.0 to 51.8 pg g(-1) fat (median: 13.1 pg g(-1) fat; mean: 18.0 pg g(-1) fat). The measurements of seven PBDE congeners (IUPAC No. 28, 47, 99, 100, 153, 154, and 183) were performed for the first time in human milk from Slovakia. PBDE levels ranged between 0.22 and 1.62 ng g(-1) fat, with median and mean value of 0.43 ng g(-1) fat and 0.57 ng g(-1) fat respectively. No statistically significant differences were observed between studied areas in total PBDE concentrations. Furthermore, this study presents first results concerning the daily intake (DI) of PCDDs/PCDFs and dioxin-like compounds for the most vulnerable breast-fed infant population in Slovakia. The total PCDD/PCDF and dl-PCB DI for an infant during the first 2 months of life was estimated in a range from 14.4 to 230 pg TEQ kg(-1)b.w., with a median value of 58.9 pg TEQ kg(-1)b.w.. The DI values substantially exceeded the tolerable daily intake (TDI) 1-4 pg TEQ kg(-1)b.w. recommended by WHO. The dietary infant intake concerning PBDEs was estimated to be between 0.69 and 7.1 ng kg(-1)b.w.d(-1), with median value of 1.7 ng kg(-1)b.w.d(-1).
Taraxacum officinale (L.) Weber ex F.H. Wigg. is commonly used in Jordan folk medicine for the treatment of panophthalmitis, chronic constipation, and diabetes. In addition, herbalists prescribe the aqueous extract of Taraxacum officinale to enhance male's fertility. The current work was undertaken to investigate the validity and/or invalidity of the aqueous extract of Taraxacum officinale on enhancing the reproductive activity in male rat.
Thirty three adult male rats were divided into three groups. Experimental groups received the aqueous extract of Taraxacum officinale orally for 60 days in two different sublethal doses; 1/10 LD(50) as high dose and 1/20 LD(50) as low dose, whereas the control group received distilled water.
The administration of the aqueous extract of Taraxacum officinale resulted in a significant decrease in testis weight in the two experimental groups in comparison to the control group but had no effect on body or organ weight. The extract of this plant caused a decrease of the following in the two experimental groups, compared to the control group: sperm count, motility and normal morphology, pregnancy rate and diameter and wall thickness of seminiferous tubules. Also, distortion of morphology of the seminiferous tubules and arrest in spermatogenesis was observed in the experimental groups. In addition, the percentage of sperm with damaged chromatin integrity was significantly higher in the two experimental groups.
From the present study, we can conclude that the aqueous extract of Taraxacum officinale acts as an anti-fertility agent rather than a fertility booster as prescribed by Jordanian herbalists.
The protective effects of common dandelion leaf water extract (DLWE) were investigated by carbon tetrachloride (CCl4) induced hepatitis in Sprague-Dawley rats. The animals were divided into five groups: normal control, DLWE control, CCl4 control, and two DLWE groups (0.5 and 2 g/kg bw). After 1 week of administering corresponding vehicle or DLWE, a single dose of CCl4 (50% CCl4/olive oil; 0.5 mL/kg bw) was administered 24 h before killing in order to produce acute liver injury. The DLWE treatment significantly decreased CCl4-induced hepatic enzyme activities (AST, ALT and LDH) in a dose dependent manner. Also, the obstructed release of TG and cholesterol into the serum was repaired by DLWE administration. Hepatic lipid peroxidation was elevated while the GSH content and antioxidative enzyme activities were reduced in the liver as a result of CCl4 administration, which were counteracted by DLWE administration. Furthermore, the hepatocytotoxic effects of CCl4 were confirmed by significantly elevated Fas and TNF-α mRNA expression levels, but DLWE down-regulated these expressions to the levels of the normal control. Highly up-regulated cytochrome P450 2E1 was also lowered significantly in the DLWE groups. These results indicate that DLWE has a protective effect against CCl4-induced hepatic damage with at least part of its effect being attributable to the attenuation of oxidative stress and inflammatory processes resulting from cytochrome P450 activation by CCl4.
To assess liver damages in pregnant and lactating rats and in their suckling pups, wistar female rats were given through drinking water 350 ppm of CoCl(2) (157 ppm Co(2+)) from the 14th day of pregnancy until day 14 after delivery. The effects of cobalt chloride on lipid peroxidation levels, antioxidant enzyme activities, lipid profile and histopathology aspects of liver were evaluated. Biochemical results showed that lipid peroxidation increased significantly in Co-treated rats, as evidenced by high liver thiobarbituric acid-reactive substance (TBARS) levels. Alteration of the antioxidant system in treated group was confirmed by the significant decline of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities and reduced glutathione (GSH) content in liver of suckling pups and their mothers. Moreover, CoCl(2) exposure induced an increase in the activities of the aspartate transaminase (AST), alanine transaminase (ALT), lactate deshydrogenase (LDH) and bilirubin levels in pups and their mothers while liver LDH activity and plasma albumin level were significantly decreased. On the other hand, cobalt chloride induced a marked hypoglycemia, a significant decline in triglycerides and total cholesterol levels. Histological studies showed an infiltration of mononuclear cells and vascular congestion in liver of pups and their mothers. Based on the present findings, exposure of rats to CoCl(2) during late pregnancy and early postnatal period affects antioxidant enzyme activities and lipid peroxidation indicating liver damage in mothers and their offspring.
To assess the co-effect of Se and Zn on Cd accumulation in the liver and kidney and on their histology, male rats were exposed either to Cd, Cd+Zn, Cd+Se, or Cd+Zn+Se in their drinking water, during 35 days. Exposure to Cd resulted in its accumulation in the liver and kidney. In the Cd-Zn and Cd-Zn-Se groups, Cd contents in the two organs were significantly (p < 0.01) higher than those in the Cd group. Se did not induce any significant difference in hepatic and renal concentrations of Cd in comparison to Cd-treated group. Light microscopic examination indicated severe histological changes in the two organs under Cd influence. Se or Zn partially alleviated the damage observed in the liver. The same effect was remarked in the kidney with Se, but no differences in the renal histological structure have been observed between the Zn-Cd and the control groups. With Se and Zn simultaneous treatment during Cd exposure, the observed morphological changes had practically disappeared from the liver, but were only reduced in the kidney. CONCLUSION: Se and Zn can have a cooperative effect in the protection against Cd-induced structural damage in the liver but not in the kidney.
The relationship between prenatal low-level lead exposure and fetal growth was evaluated in a sample of 4354 pregnancies in which the mean umbilical cord blood lead level was 7.0 micrograms/dl (SD = 3.3; 10th percentile, 3.4 micrograms/dl, 90th percentile, 10.9 micrograms/dl). Higher cord blood lead levels were significantly associated with gestations of slightly longer duration. Comparing infants with cord blood lead levels greater than or equal to 15 micrograms/dl to those with levels less than 5 micrograms/dl, adjusted risk ratios of 1.5 to 2.5 were observed for low birth weight (less than 2500 g) and for fetal growth indices that express birth weight as a function of length of gestation (e.g., small-for-gestational age, intrauterine growth retardation). The 95% confidence intervals of these risk ratios included 1, however, precluding rejection of the null hypothesis of no association. We conclude that the risk of adverse fetal growth is not increased at cord blood lead levels less than 15 micrograms/dl but that modest increases in risk may be associated with levels greater than or equal to 15 micrograms/dl.
Neurotoxicity is the major health effect from exposure to lead for infants and young children, and there is current concern regarding possible toxic effects of lead on the child while in utero. There is no placental-fetal barrier to lead transport. Maternal and fetal blood lead levels are nearly identical, so lead passes through the placenta unencumbered. Lead has been measured in the fetal brain as early as the end of the first trimester (13 weeks). There is a similar rate of increase in brain size and lead content throughout pregnancy in the fetus of mothers in the general population, so concentration of lead probably does not differ greatly during gestation unless exposure of the mother changes. Cell-specific sensitivity to the toxic effects of lead, however, may be greater the younger the fetus. Lead toxicity to the nervous system is characterized by edema or swelling of the brain due to altered permeability of capillary endothelial cells. Experimental studies suggest that immature endothelial cells forming the capillaries of the developing brain are less resistant to the effects of lead, permitting fluid and cations including lead to reach newly formed components of the brain, particularly astrocytes and neurons. Also, the ability of astrocytes and neurons to sequester lead in the form of lead protein complexes occurs only in the later stages of fetal development, permitting lead in maturing brain cells to interact with vital subcellular organelles, particularly mitochondria, which are the major cellular energy source. Intracellular lead also affects binding sites for calcium which, in turn, may affect numerous cell functions including neurotransmitter release.
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This paper addresses several methodological issues relevant to an assessment of the association between low-level lead exposure and early development. In particular, we discuss methods for choosing, from a large pool of candidates, the covariates to control when estimating this association. We examine the issue of confounding and explain why adjusting increased, rather than decreased, the estimate of the association between blood lead level and development at 6 months of age in our sample. A step-by-step description of our strategy for model building is presented. Finally, we demonstrate the robustness of the findings by showing that the magnitude and standard error of the estimated lead effect is not affected appreciably by the method of selecting covariates to be controlled for or by the characterization of lead as a continuous, ordinal, or dichotomous variable. Although these issues arose in the course of analyses of data collected by the Boston lead study (D. Bellinger, H. Needleman, A. Leviton, C. Waternaux, M. Rabinowitz, and M. Nichols (1984), Neurobehav. Tox. Teratol., 6, 387-402), they apply to other current prospective lead studies as well.
Smelter workers are exposed to a number of metals and other substances in dust, fumes and gases. The concentrations of lead in liver, lung, kidney, brain, hair and nails were determined in 32 deceased, long-term exposed male lead smelter workers, and compared with those of 10 male controls. The lead levels in liver, lung, kidney and brain were analyzed by atomic absorption spectrophotometry. X-ray fluorescence was used for the determinations in hair and nails. Lead in blood had been determined repeatedly in the lead workers since 1950, which made it possible to calculate a time-integrated blood lead index for each worker. The highest lead levels in soft tissues were found in liver, followed in order of concentration by kidney, lung and brain, among both exposed workers and controls. These organ lead concentrations were all significantly higher among the workers as compared with the control group (p < or = 0.02). The largest difference between workers and controls was found in brain tissue (ratio between median values = 5.6). The lead levels in hair and nails were of the same magnitude in the two groups. The workers showed positive correlations between lead concentrations in liver and kidney (Spearman's rho = rs = 0.59; p < 0.001), liver and hair (rs = 0.51; p = 0.003), liver and nails (rs = 0.52; p = 0.002) and hair and nails (rs = 0.52; p = 0.002). Lead concentrations in kidney correlated well with lead levels in hair (rs = 0.57; p = 0.001) and nails (rs = 0.51; p = 0.003), respectively. The positive correlation between the lead concentrations in liver and kidney indicates that these organs belong to the same soft tissue lead pool in the body. In retired lead workers, positive correlations were observed between the lead concentrations in liver and the cumulative blood lead index (CBLI) (rs = 0.50; p = 0.016), as well as between lead levels in kidney and CBLI (rs = 0.51; p = 0.014).
This paper examines the quantitative relationships between dust loading, lead loading, and lead concentration in house dust. Bare floor, interior sill, and carpet dust samples were collected in 216 Jersey City, New Jersey, homes using quantitative wipe and vacuum sampling techniques. Comparison of wipe and vacuum sample distributions for these homes indicated that lead loading was more variable than dust loading or lead concentration measured on floors, sills, or carpets. These data also indicated that increased lead loading on carpets relative to sills or floors was due to higher dust loading on carpets. Correlation analysis of wipe samples indicated that dust loading was more strongly correlated with lead loading on floors (r = 0.73) than on sills (r = 0.53), that dust loading was not correlated with lead concentration on either surface, and that lead loading and lead concentration were more strongly correlated in samples collected from sills (r = 0.81) than from floors (r = 0.65). Most importantly, carpets and rugs served as large reservoirs for house dust and consequently were a large potential source of dust exposure in children's common microenvironments.
The phytotherapy should be understood as being integrated into the rational pharmacotherapy. The modern phytotherapy tries hard to proof effects with pharmacological and clinical studies. The task force E of the federal bureau of health of Germany has made a statement regarding this problem. This article reviews only controlled clinical trials about the application of extracts of echinacea purpura or echinacea pallida.
Three flavonoid glycosides: luteolin 7-glucoside and two luteolin 7-diglucosides were isolated from dandelion flowers and leaves together with free luteolin and chrysoeriol in the flower tissue. The hydroxycinnamic acids, chicoric acid, monocaffeyltartaric acid and chlorogenic acid were found throughout the plant and the coumarins, cichoriin and aesculin were identified in the leaf extracts. This represents the first report of free chrysoeriol (luteolin 3'-methyl ether) in Taraxacum officinale agg. An earlier provisional identification of chicoric acid, chlorogenic acid, cichoriin and aesculin in a phenolic survey of the tribe Cichorieae is confirmed. Chicoric acid and the related monocaffeyltartaric acid were found to be the major phenolic constituents in flowers, roots, leaves and involucral bracts and also in the medicinal preparations tested.
The absorption and disposition of lead in blood was examined in 10-day-old suckling mice exposed via milk. Lactating dams were administered a single intravenous injection of 0.05 mg Pb (2.5 mCi 203Pb)/kg body wt. Lead concentrations in blood of the suckling offspring were measured for 10 days after administration to the dams. Maximum blood lead concentrations in the pups were recorded between 50 and 74 hr after dams' administration despite the fact that the majority of the lead dose to the sucklings was delivered within 24 hr after dams' administration. Kinetic analysis of pups' blood lead data revealed a rate-limited absorption in the suckling pups with an absorption half-life of approximately 17 hr in the pups. This delayed absorption is most likely due to a retention of casein-bound lead in the ileal mucosa which has a high pinocytotic activity of dietary proteins in infant rodents. The present results also indicated that the distribution of lead to the peripheral tissues in the suckling mice was different than that of adults. The conflicting evidence on whether milk enhances or inhibits the absorption of lead in infant rodents may thus be explained by measurements of lead absorption at different time periods after administration to the animals. It is also suggested that the milk diet is one reason for the increased absorption of lead seen in immature rodents.
The potential human health risk of lead in the environment remains a topic of current debate and concern. Given sufficient exposure, lead can exert severe and chronic health effects. Today, due to successful efforts to reduce the commercial use of lead and control its release to the environment, lead "poisoning" is uncommon in our society. Blood-lead levels among the U.S. population, including those of children, have decreased dramatically over the past decade and according to current surveillance programs continue to decline. Because lead poisoning among children is no longer as prevalent as it once was, the focus has shifted to the long-term effects lead may exert on the intellectual development of children. Continued toxicological and epidemiological research will expand the understanding of this important facet of the lead issue. Trace levels of lead in consumer products remain a low health risk to humans, despite the fear and uncertainty which often accompany such concerns. Future efforts to reduce lead exposure should be aimed at high-risk groups which include the socioeconomically disadvantaged and certain minority sectors of the population. Through educational programs, improvement in personal hygiene practices, and abatement of lead-containing paint (when warranted), blood lead levels should continue to decline, reducing the health risk to lead in the environment.
To determine how chronic alcohol administration during lactation affects milk composition and the nutritional status of the dam, EtOH (3 g/kg) as a 20% solution was administered by intubation to Sprague-Dawley rats from days 2 through 15 of lactation. Control dams were pair fed to account for the reduction in food intake observed in the alcohol group, while another control group maintained ad lib food intake. Dams and their litters were weighed daily throughout the study. On day 16, dams were sacrificed and samples taken for further analysis. Blood alcohol levels as well as serum levels of calcium, cholesterol, glucose, iron, lipids, phosphorous, and triglycerides were measured. Liver lipid levels and the total composition and fatty acid profile of the phospholipids in milk were also measured. Results indicate that EtOH administration and pair feeding reduced dam body weight, but not litter growth. Serum iron levels was increased in both EtOH-exposed and pair-fed controls, whereas serum cholesterol was elevated only in EtOH-exposed dams. Finally, of the phospholipids in milk, only one, phosphatidylserine, was slightly but significantly increased by EtOH. If and how these changes impact the development of the offspring remain to be studied.
Reactive oxygen species are widely generated in biological systems. Consequently humans have evolved antioxidant defence systems that limit their production. Intracellular production of active oxygen species such as *OH, O2- and H2O2 is associated with the arrest of cell proliferation. Similarly, generation of oxidative stress in response to various external stimuli has been implicated in the activation of transcription factors and to the triggering of apoptosis. Here we review how free radicals induce DNA sequence changes in the form of mutations. deletions, gene amplification and rearrangements. These alterations may result in the initiation of apoptosis signalling leading to cell death, or to the activation of several proto-oncogenes and or the inactivation of some tumour suppressor genes. The regulation of gene expression by means of oxidants, antioxidants and the redox state remains as a promising therapeutic approach. Several anticarcinogenic agents have been shown to inhibit reactive oxygen species production and oxidative DNA damage, inhibiting tumour promotion. In addition, recombinant vectors expressing radical-scavenging enzymes reduce apoptosis. In conclusion, oxidative stress has been implicated in both apoptosis and the pathogenesis of cancer providing contrived support for two notions: free radical reactions may be increased in malignant cells and oxidant scavenging systems may be useful in cancer therapy.
Despite a steady decline in average blood lead levels in the U.S. population, approximately 0.5% of women of childbearing age may have blood levels exceeding 10 microg/dl. Strong correlations between maternal and umbilical cord blood lead levels demonstrate that lead is transferred from the mother to the fetus. High lead levels are known to cause neurobehavioral effects in infants and children, and the cumulative effects of low levels of lead exposure in utero and after birth can have similar detrimental effects. Modern sources of exposure include occupational exposure during automotive or aircraft paint manufacturing, lead production or smeltering, exposure to stained glass soder, and environmental exposure during home renovation. Prenatal screening for lead exposure may include use of a five-item questionnaire similar to the pediatric questionnaire. Management of prenatal lead exposure focuses on removal of the lead source. Rarely, highly toxic chelation therapy is needed for maternal indications. Recognition and removal of lead sources during the prenatal period can prevent maternal and neonatal morbidity.
Dandelion water extract (DWE), an herbal medication, may have an effect on the activity and mRNA expression of hepatic antioxidant enzymes and lipid profile in streptozotocin (STZ)-induced diabetic rats.
Male Sprague-Dawley rats were divided into nondiabetic (control), diabetic, and diabetic-DWE-supplemented groups. Diabetes was induced by injecting streptozotocin (55 mg/kg BW, i.p.) in a citrate buffer. The extract was supplemented in 2.4 g of a DWE/kg diet.
The DWE supplement significantly decreased the serum glucose concentration in the diabetic rats. The hepatic superoxide dismutase and catalase activities significantly increased and the GSH-Px activity decreased in the diabetic rats, compared with the control group. When the DWE supplement was given to the diabetic rats, the antioxidant enzyme activity reverted to near-control values. However, there was no difference in the mRNA expression concentrations of these enzymes between the groups. With regard to the hepatic lipid peroxidation product, the malondialdehyde (MDA) content was significantly higher in the diabetic group than in the nondiabetic group. However, the DWE supplement lowered the hepatic MDA concentration in the diabetic-induced rats. The DWE supplement also lowered the total cholesterol and triglyceride concentrations in the serum and hepatic tissue, while increasing the serum HDL-cholesterol in the diabetic rats.
A DWE supplement can improve the lipid metabolism and is beneficial in preventing diabetic complications from lipid peroxidation and free radicals in diabetic rats.
Phytoestrogens such as the soy isoflavonoid daidzein have potential health benefits. The antioxidant properties of phytoestrogens are considered to be responsible in part for their protective effects. The antioxidant enzyme (AOE) system plays an important role in the defense of cells against oxidative insults. To determine whether flavonoids can exert antioxidative effects not only directly but also indirectly by modulating the AOE system, we investigated the influence of the flavonoid daidzein on the expression of different AOE. Daidzein treatment of hepatoma H4IIE cells increased catalase mRNA expression two- to threefold. Expression levels of copper zinc superoxide dismutase (CuZnSOD) were not affected by exposure to daidzein. Manganese superoxide dismutase (MnSOD) mRNA expression levels decreased slightly and glutathione peroxidase (GPx) levels increased slightly after daidzein exposure. Changes in AOE mRNA expression levels were significant at 300 micromol/L daidzein. To elucidate the mechanisms underlying the strong increase in catalase mRNA, transfection experiments were performed. Transient transfection of hepatoma cells with reporter plasmids containing different parts of the upstream region of the catalase gene showed a significant one- to threefold increase in reporter gene activity after daidzein exposure. This indicates that daidzein can directly activate the rat catalase promoter region. Despite the increase in catalase mRNA, daidzein pretreatment of cells did not protect against oxidative stress resulting from H(2)O(2) exposure. On the contrary, daidzein itself exerted a mild oxidative stress. In conclusion, the changes in the AOE system provoked by daidzein affected the oxidant rather than the antioxidant properties of daidzein.
The toxic effects derived from overproduction of oxygen radicals [reactive oxygen species (ROS)] by immune cells can be partially abolished by the antioxidant activities of plant polyphenols. In the present study, we investigated the antioxidant action of a catechin, (-)-epigallocatechin-3-gallate (EGCG), on the respiratory-burst responses of rat peritoneal macrophages. EGCG at concentrations of 50-200 microM blocked the production of nitric oxide by macrophages stimulated in vivo with sodium thioglycollate then 5 days later in vitro with lipopolysaccharide and gamma-interferon. At 1-100 microM, EGCG also inhibited the extracellular liberation of oxygen radicals by resident peritoneal macrophages stimulated with the protein kinase C activator phorbol 12-myristate 13-acetate (PMA). At low concentrations (1-5 microM), EGCG increased the reduction of nitro blue tetrazolium (NBT) by the superoxide anions generated in the non-enzymatic system NADH/PMS, acting as a pro-oxidant agent, while at concentrations above 10 microM, EGCG acts as a scavenger of superoxide anions. These results show that EGCG is capable of modulating ROS production during the respiratory burst of rat peritoneal macrophages by acting as a superoxide anion scavenger. EGCG may therefore be useful in the prevention and treatment of diseases due to increased free radical production.