-
[show abstract]
[hide abstract]
ABSTRACT: 3-methyl-2-quinoxalin benzenevinylketo-1, 4-dioxide (Quinocetone, QCT) is a newly used veterinary drug which has been proven to promote feed efficiency and growth of animals; however, its potential toxicity can't be ignored. Therefore, the present study was aimed to investigate the nephrotoxicity of QCT and the oxidative stress induced by it. Sprague-Dawley rats (SD rats) were randomly divided into 4 groups with doses of 2400, 800, 50 and 0 mg/kg/day with administration of QCT for 4 weeks. Results proved that QCT could induce nephrotoxicity and this phenomenon had dose dependent manner. Simultaneously, this phenomenon was accompanied by intracellular reactive oxygen species (ROS) accumulation, enhanced lipid peroxidation and inhibited antioxidant system, i.e. glutathione S-transferase (GST), glutathione peroxidase (GPx) and glutathione reductase (GSH). Additionally, the higher expression of Nrf2 in QCT treated groups illustrated that QCT-induced oxidative stress would be partly mitigated by the induction of phase II detoxifying enzymes via increasing Nrf2 expression.
Regulatory Toxicology and Pharmacology 04/2013; · 2.43 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: ETHNOPHARMACOLOGICAL RELEVANCE: Pu-erh black tea, which is obtained by first parching crude green tea leaves and followed by secondary fermentation with microorganisms, has been believed to be beneficial beverages for health in P.R. China. But its potential toxicity when administered at a high dose as concentrated extract has not been completely investigated. AIM OF THE STUDY: The present study was aimed at evaluating potential reproductive and developmental toxicities of Pu-erh black tea extract (BTE) in Sprague Dawley rats. MATERIALS AND METHODS: Growing rats were given BTE by gavage at levels of 0, 200, 700 and 2500mg/kg/day as the F0 generation in reproductive toxicity study. Additionally, BTE was administered to mate female rats from gestation day 0.5 through 19.5 at the doses of 0, 200, 700 and 2500mg/kg/day to evaluate the developmental toxicity. RESULTS: In the reproductive toxicity study, only 2500mg/kg/day BTE reduced the body weight gain and altered the relative organ weights including testes, prostata and ovary both for F0 parents and F1 offspring compared to the controls. High dose of BTE (2500mg/kg/day) administration caused developmental disturbances in embryo-to- foetus period including resorbed embryos, decreased embryo size and skeletal anomalies. CONCLUSION: In conclusion, the no-observed-adverse-effect level of BTE is 700mg/kg/day both for reproductive toxicity and developmental toxicities.
Journal of ethnopharmacology 04/2013; · 2.32 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Naturally occuring quercetin protects hepatocytes from ethanol-induced oxidative stress, and heme oxygenase-1 (HO-1) induction and carbon monoxide (CO) metabolite may be implicated in the beneficial effect. However, the precise mechanism by which quercetin counteracts CYP2E1-mediated ethanol hepatotoxicity through HO-1 system is still remained unclear. To explore the potential mechanism, herein, ethanol (4.0g/kg.bw.) was administrated to rats for 90 days. Our data showed that chronic ethanol over-activated CYP2E1 but suppressed HO-1 with concurrent hepatic oxidative damage, which was partially normalized by quercetin (100mg/kg.bw.). Quercetin (100μM) induced HO-1 and depleted heme pool when incubated to human hepatocytes. Ethanol-stimulated (100mM) CYP2E1 upregulation was suppressed by quercetin but further enhanced by HO-1 inhibition with resultant heme accumulation. CO scavenging blocked the suppression of quercetin only on CYP2E1 activity. CO donor dose-dependently inactivated CYP2E1 of ethanol-incubated microsome, which was mimicked by HO-1 substrate but abolished by CO scavenger. Thus, CYP2E1-mediated ethanol hepatotoxicity was alleviated by quercetin through HO-1 induction. Depleted heme pool and CO releasing limited protein synthesis and inhibited enzymatic activity of CYP2E1, respectively.
Phytomedicine: international journal of phytotherapy and phytopharmacology 04/2013; · 2.17 Impact Factor
-
Xiang Li,
Xiaolei Wang,
Rui Liu,
Yan Ma,
Huailan Guo,
Liping Hao, Ping Yao,
Liegang Liu,
Xiufa Sun,
Ka He,
Wenhong Cao,
Xuefeng Yang
[show abstract]
[hide abstract]
ABSTRACT: SCOPE: This study investigated the effect of chronic leucine supplementation on insulin sensitivity and the associated mechanisms in rats on high-fat diet (HFD). METHODS AND RESULTS: Male Sprague-Dawley rats were fed either normal chow diet or HFD supplemented with 0, 1.5, 3.0, and 4.5% leucine for 24 weeks. We found that chronic leucine supplementation increased insulin sensitivity together with increased body weight in rats on HFD, but had no effect on insulin sensitivity in rats on normal chow diet. The increased insulin sensitivity by leucine supplementation was not associated with altered ectopic fat accumulation in liver and muscle, plasma levels of lipids and cytokines, but is associated with reduced oxidative stress and improved insulin signaling. Chronic leucine supplementation did not enhance insulin receptor substract-1 (IRS-1) phosphorylation on serine 302, but elevated basal IRS-1 phosphorylation on tyrosine 632 and improved insulin-stimulated protein kinase B (Akt) and mammalian target of rapamycin (mTOR) phosphorylation in liver, skeletal muscle, and adipose tissue of rats on HFD rats, indicating leucine supplementation prevented HFD-induced insulin resistance in insulin-target tissues. CONCLUSION: Chronic leucine supplementation can increase insulin sensitivity and body weight likely by reducing oxidative stress and improving insulin signaling pathway in rats on HFD.
Molecular Nutrition & Food Research 02/2013; · 4.30 Impact Factor
-
Xuefeng Yang,
Shuang Mei,
Xiaolei Wang,
Xiang Li,
Rui Liu,
Yan Ma,
Liping Hao, Ping Yao,
Liegang Liu,
Xiufa Sun,
Haihua Gu,
Zhenqi Liu,
Wenhong Cao
[show abstract]
[hide abstract]
ABSTRACT: In this study, we addressed the direct effect of leucine on insulin signaling. In investigating the associated mechanisms, we found that leucine itself does not activate the classical Akt-or ERK1/2 MAP kinase-dependent signaling pathways but can facilitate the insulin-induced phosphorylations of Akt473 and ERK1/2 in a time- and dose-dependent manner in cultured hepatocytes. The leucine-facilitated insulin-induced phosphorylation of Akt at residue 473 was not affected by knocking down the key component of mTORC1 or 2 complexes, but was blocked by inhibition of c-Src (PP2), PI3K (LY294002), Gαi protein (pertussis toxin or siRNA against Gαi1 gene, or β-arrestin 2 (siRNA). Similarly, the leucine-facilitated insulin activation of ERK1/2 was also blunted by pertussis toxin. We further show that leucine facilitated the insulin-mediated suppression of glucose production and expression of key gluconeogenic genes in a Gαi1 protein-dependent manner in cultured primary hepatocytes. Together, these results show that leucine can directly facilitate insulin signaling through a Gαi protein-dependent intracellular signaling pathway. This is the first evidence showing that macronutrients like amino acid leucine can facilitate insulin signaling through G proteins directly.
Journal of Biological Chemistry 02/2013; · 4.77 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: OBJECTIVES: This systematic review and meta-analysis was conducted to estimate the effects of intravenous and nebulized magnesium sulfate on treating adults and children with acute asthma. METHODS: Electronic literature search and the manual search of key respiratory journals were performed up to October 18, 2011. Randomized controlled trials were included if patients had been treated with intravenous or nebulized magnesium sulfate in combination with β2-agonists and were compared with the use of β2-agonists. Standardized mean differences (SMDs) and the relative risks (RRs) were calculated for pulmonary functions and hospital admission respectively. RESULTS: 25 trials (16 intravenous, 9 nebulized) involving 1754 patients were included. In adults intravenous treatment was associated with a significant effect upon respiratory function (SMD, 0.30; 95% confidence interval (CI), 0.05 to 0.55; p = 0.02) but weak evidence of effect upon hospital admission (RR 0.86,95% CI 0.73 to 1.01; p = 0.06) in adults, and in children with significant effects upon both respiratory function (SMD, 1.94; 95% CI, 0.80 to 3.08; p = 0.0008) and hospital admission (RR, 0.70; 95% CI, 0.54 to 0.91; p = 0.008). Nebulized treatment was associated with significant effects upon respiratory function (SMD, 0.23; 95% CI, 0.06 to 0.41; p = 0.009) and hospital admission (RR, 0.63; 95% CI, 0.43 to 0.92; p = 0.02) in adults. CONCLUSION: The use of intravenous magnesium sulfate, in addition to β2-agonists and systemic steroids, in the treatment of acute asthma appears to produce benefits with respect to improve pulmonary function and reduce the number of hospital admissions for children, and only improve pulmonary function for adults. However, the use of nebulized magnesium sulfate just appears to produce benefits for adults.
Respiratory medicine 01/2013; · 2.33 Impact Factor
-
Xia Wang,
Wei Bao,
Jun Liu,
Ying-Ying Ouyang,
Di Wang,
Shuang Rong,
Xiao Xiao,
Zhi-Lei Shan,
Yan Zhang, Ping Yao,
Lie-Gang Liu
[show abstract]
[hide abstract]
ABSTRACT: OBJECTIVE There has been growing evidence that inflammatory markers play a role in the development of type 2 diabetes. We aimed to systematically review prospective studies on the associations of elevated levels of interleukin-6 (IL-6) and C-reactive protein (CRP) with increased risk of type 2 diabetes by conducting a meta-analysis. RESEARCH DESIGN AND METHODS A systematic search of the PubMed, EMBASE, ISI Web of Knowledge, and Cochrane Library databases up until 10 February 2012 was conducted to retrieve prospective studies matched to search terms. We used generalized least-squares trend estimation to assess dose-response relationships. The summary risk estimates were pooled using either fixed-effects or random-effects models to incorporate between-study variation. RESULTS The meta-analysis, including 10 prospective studies, with a total of 19,709 participants and 4,480 cases, detected a significant dose-response association of IL-6 levels with type 2 diabetes risk (relative risk [RR] 1.31 [95% CI 1.17-1.46]). For CRP, the meta-analysis involving 22 cohorts, with a total of 40,735 participants and 5,753 cases, showed that elevated CRP levels were significantly associated with increased risk of type 2 diabetes (1.26 [1.16-1.37]), with the absence of publication bias. Sensitivity and subgroup analyses further supported the associations. CONCLUSIONS This meta-analysis provides further evidence that elevated levels of IL-6 and CRP are significantly associated with increased risk of type 2 diabetes.
Diabetes care 01/2013; 36(1):166-75. · 8.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To attenuate alcohol liver disease (ALD) is extremely urgent since ALD has been emerged as a major liver disease. The aim of the present study is to investigate the hepatoprotective effect against ethanol-induced injury of bilirubin, a product of heme metabolism degradation via HO and biliverdin reductase catalysis. Ethanol-incubated primary rat hepatocytes (100 mmol/L) were treated by quercetin, bilirubin, inflammatory factors, and/or HO-1 inducer/inhibitor for 24 h, and the cellular damage was assayed. Quercetin lowered ethanol-induced glutathione depletion and superoxide dismutase inactivation, inhibited the overproduction of malondialdehyde and reactive oxygen species, and decreased the leakage of cellular aspartate aminotransferase and lactate dehydrogenase, accompanying the normalization of bilirubin level. The effect of quercetin was mimicked by exogenous bilirubin in a dose-dependent manner to some extent (within 25 μmol/L) and pharmacological HO-1 inducer hemin, but abolished by HO-1 inhibitor zinc protoporphyrin-IX. Inflammatory challenge of TNF-α plus IL-6 further aggravated ethanol-induced oxidative damage, which was also attenuated by bilirubin in part. These findings shed a light on the anti-oxidative and anti-inflammatory role of bilirubin released from quercetin/HO-1 and biliverdin reductase pathway against ethanol hepatotoxicity and highlight a prospective strategy of nutritional intervention for ALD by naturally occurring quercetin to induce HO-1 with the release of bioactive end-products.
Alcohol (Fayetteville, N.Y.) 12/2012; · 2.41 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: Quinocetone has been widely used as an animal growth promoter in China. However, available data showed that QCT has potential genotoxicity. This study was conducted to investigate the cytotoxicity and genotoxicity of QCT in human lymphocytes. RESULTS: CCK-8 assay demonstrated the severe inhibitory effects by QCT in a dose- and time-dependent manner. DNA damage analysis using alkalic Comet assay revealed a pronounced increase of DNA fragmentation in cells. In contrast, DNA damage was significantly decreased after incubation with S9 mix. This finding demonstrated that the intermediate metabolites of this drug exerted lower genotoxicity than its parent drugs. We further described chromosomal damage induced by this drug employing cytokinesis-block micronucleus assay. The micronucleus frequency was significantly increased in quinocetone groups as compared to controls. Similar to the observation in Comet assay, incorporation of S9 mix in the cytokinesis-block micronucleus assay could markedly alleviate the chromosomal damage. Moreover, QCT could invoke increase of reactive oxygen species generation in cells. Intriguingly, the toxicity of QCT was more prominent in samples from males than those from females under the same conditions. CONCLUSION: QCT could induce potential cytotoxicity and genotoxicity in human lymphocytes.
Journal of the Science of Food and Agriculture 08/2012; · 1.44 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The hemochromatosis gene (HFE) has been involved in the etiology of type 2 diabetes mellitus and investigated in numerous epidemiologic studies. The current meta-analysis was conducted to evaluate the gene-disease association in relevant studies. Electronic literature search was performed on June 18, 2011, from databases of PubMed/MEDLINE, EMBASE, and HuGE Navigator. Articles were inspected by 2 authors independently, and data were extracted by identical extraction form. A total of 5,528 type 2 diabetes cases and 6,920 controls in relation to HFE polymorphisms (a cysteine to tyrosine substitution at amino acid position 282 (C282Y) and a histidine to aspartate substitution at amino acid position 63 (H63D)) were included in the meta-analysis (1997-2011). A fixed- or random-effect model was used to calculate the pooled odds ratios based on the results from the heterogeneity tests. An increased odds ratio for type 2 diabetes mellitus was observed in persons carrying a D allele at the H63D polymorphism compared with those with an H allele (odds ratio (OR) = 1.21, 95% confidence interval (CI): 1.03, 1.41; P = 0.02). Moreover, carriers of a D allele had a modestly increased risk compared with persons with the wild genotype (OR = 1.12, 95% CI: 1.00, 1.25; P = 0.04). The C282Y variant was not significantly associated with diabetes risk. In summary, persons with a D allele may have a moderately increased risk of type 2 diabetes mellitus.
American journal of epidemiology 08/2012; 176(6):461-72. · 5.59 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The erythrocyte membrane lesion is a serious diabetic complication. A number of studies suggested that n-3 fatty acid could reduce lipid peroxidation and elevate α- or γ-tocopherol contents in membrane of erythrocytes. However, evidence regarding the protective effects of flaxseed oil, a natural product rich in n-3 fatty acid, on lipid peroxidation, antioxidative capacity and membrane deformation of erythrocytes exposed to high glucose is limited.
Human peripheral blood erythrocytes were isolated and treated with 50 mM glucose to mimic hyperglycemia in the absence or presence of three different doses of flaxseed oil (50, 100 or 200 μM) in the culture medium for 24 h. The malondialdehyde (MDA) and L-glutathione (GSH) were measured by HPLC and LC/MS respectively. The phospholipids symmetry and membrane fatty acid composition of human erythrocytes were detected by flow cytometry and gas chromatograph (GC). The morphology of human erythrocyte was illuminated by ultra scanning electron microscopy.
Flaxseed oil attenuated hyperglycemia-induced increase of MDA and decrease of GSH in human erythrocytes. Human erythrocytes treated with flaxseed oil contained higher C22:5 and C22:6 than those in the 50 mM glucose control group, indicating that flaxseed oil could reduce lipid asymmetric distribution and membrane perturbation. The ultra scanning electron microscopy and flow cytometer have also indicated that flaxseed oil could protect the membrane of human erythrocytes from deformation at high glucose level.
The flaxseed oil supplementation may prevent lipid peroxidation and membrane dysfunction of human erythrocytes in hyperglycemia.
Lipids in Health and Disease 07/2012; 11:88. · 2.17 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Lipid metabolism disorder and oxidative stress play an important role on the development and progression of alcoholic liver disease (ALD), and mitochondria compartment is presumed as the main source and susceptible target of intracellular ROS. The objective of this study was to evaluate the protective effect of quercetin, a naturally occurring flavonoids possessing both antioxidant and hypolipidemic effect, on ethanol-induced dyslipidemia and oxidative damage focused on mitochondria. Chronic alcohol administration for adult male rats (4.0 g/kg for 90 days) resulted in the leakage of alanine and especially aspartate aminotransferases, and morphological malformation mainly evidenced by sustained lipid infiltration and degenerative changes on mitochondria and rough endoplasmic reticulum, which was markedly alleviated by quercetin (100 mg/kg.bw.) pretreatment. Furthermore, quercetin prophylaxis evidently ameliorated ethanol-stimulated mitochondrial dysfunction manifested by decreased membrane potential and induced permeability transition though suppressing glutathione depletion, enzymatic inactivation of manganese superoxide dismutase and glutathione peroxidase, ROS over-generation, and lipid peroxidation in mitochondria. Quercetin, thus, may protect rat, especially hepatic mitochondria, from chronic ethanol toxicity through its hypolipidemic effect and antioxidative role, highlighting a promising preventive strategy for ALD by naturally occurring phytochemicals.
Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 02/2012; 50(5):1194-200. · 2.99 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Persimmon proanthocyanidin was fractionated on Toyopearl TSK-HW-50-F to yield a fraction with strong inhibition on the catalytic activity and edema-inducing activity and lethality of Chinese cobra PLA(2). Thiolysis suggested that the terminal units included C, EGCG and myricetin, and epicatechin, epigallocatechin, (epi)gallocatechin-3-O-gallate, and (epi)catechin-3-O-gallate occurred as extender units. The mean degree of polymerization was 23.7. MALDI TOF/MS, thioly-HPLC, FTIR and circular dichroism (CD) analyses showed that the fraction had high prodelphinidin content (55%) and a very high degree of 3-O-galloylation (92%). A type linkage is dominant in it and it had 4β linkage of the flavanyl substituent and 4R absolute configuration.
Fitoterapia 01/2012; 83(1):153-60. · 1.85 Impact Factor
-
Wei Bao,
Shuang Rong,
Muxun Zhang,
Xuefeng Yu,
Yanting Zhao,
Xiao Xiao,
Wei Yang,
Di Wang, Ping Yao,
Frank B Hu,
Liegang Liu
[show abstract]
[hide abstract]
ABSTRACT: Our previous study has recently shown that plasma heme oxygenase-1 (HO-1), a stress-responsive protein, is elevated in individuals with type 2 diabetes. The current study aimed to examine the association between plasma HO-1 concentration and impaired glucose regulation (IGR) in non-diabetic individuals.
We conducted a case-control study including a total of 865 subjects (262 IGR individuals and 603 healthy controls) in a Chinese population. Basic characteristics were collected by questionnaire and standardized anthropometric measurements. Plasma HO-1 concentration was determined by ELISA.
Plasma HO-1 concentration was significantly increased in IGR individuals compared with healthy controls (1.34 (0.81-2.29) ng/ml vs 0.98 (0.56-1.55) ng/ml, P<0.001). After adjustment for age, sex, and BMI, the ORs for IGR in the highest quartile of plasma HO-1 concentrations, compared with the lowest, was 3.42 (95% CI 2.11-5.54; P for trend <0.001). The trend remained significant even after additional adjustment for smoking, alcohol drinking, hypertension, family history of diabetes, lipid profiles and C-reactive protein. In the receiver-operating characteristic curve analysis, addition of plasma HO-1 concentration to a model with known risk factors yielded significantly improved discriminative value for IGR (area under the curves 0.75 (95% CI 0.71-0.78) vs. 0.72 (95% CI 0.69-0.76); P for difference = 0.026).
Elevated plasma HO-1 concentration is significantly associated with increased ORs for IGR. However, its clinical utility should be validated in further studies, especially in prospective cohort studies.
PLoS ONE 01/2012; 7(3):e32223. · 4.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Curcumin has a variety of pharmacological effects. However, poor water solubility and low oral bioavailability limit its clinical utility. A delivery system for nanostructured lipid carriers has been reported to be a promising approach to enhancing the oral absorption of curcumin. The aim of the present study was to investigate the pharmacokinetics, tissue distribution, and relative bioavailability of curcumin in rats after a single intragastric dose of a nanostructured lipid curcumin carrier formulation.
Nanostructured lipid curcumin carriers were prepared using the ethanol dripping method and characterized in terms of the particle size, polydispersity index, zeta potential, differential scanning calorimetry, drug-loading capacity, encapsulation efficiency, and in vitro release. The pharmacokinetics and tissue distribution of nanostructured lipid curcumin carriers and curcumin suspension were compared after intragastric administration.
Nanostructured lipid curcumin carriers showed a significantly higher peak plasma concentration (564.94 ± 14.98 ng/mL versus 279.43 ± 7.21 ng/mL, P < 0.01), a shorter time taken to reach peak plasma concentration (0.5 ± 0.01 hour versus 1.0 ± 0.12 hour, P < 0.01), and a greater AUC(0-∞) (820.36 ± 25.11 mg × hour/L versus 344.11 ± 10.01 mg × hour/L, P < 0.05) compared with curcumin suspension. In the tissue distribution studies, curcumin could be detected in the spleen, heart, liver, kidneys, lungs, and brain. Following intragastric administration of the nanostructured lipid curcumin carrier formulation, tissue concentrations of curcumin also increased, especially in the brain. The nanostructured lipid curcumin carrier formulation improved the ability of curcumin to cross the blood-brain barrier, with an 11.93-fold increase in the area under the curve achieved in the brain when compared with curcumin suspension.
The nanostructured lipid carrier formulation significantly improved the oral bioavailability of curcumin and represents a promising method for its oral delivery.
International Journal of Nanomedicine 01/2012; 7:5395-404. · 3.13 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: 3-Methyl-2-quinoxalin benzenevinylketo-1,4-dioxide (Quinocetone, QCT), has been used to treat dysentery and promote growth in animal feeding. However, available data show that QCT has potential nephrotoxicity. The present study was designed to investigate the protective effects of Pu-erh black tea extract (PBTE) which is a traditional remedy in China with antioxidant properties against oxidative DNA damage and oxidative stress in a rat model of QCT-induced renal dysfunction. Increased serum creatinine, blood urea nitrogen, pathological lesions, urinary 8-hydroxy 2-deoxyguanosine (8-OHdG) and renal DNA damage were observed in the QCT-fed rats. These were accompanied by intracellular reactive oxygen species accumulation, enhanced lipid peroxidation, and inhibited antioxidant system, i.e., glutathione glutathione S-transferase, glutathione peroxidase and glutathione reductase. Oral administration of PBTE effectively suppressed QCT-induced renal dysfunction, as evidenced by reduced serum creatinine, urinary 8-OHdG and DNA damage in isolated renal cells, amelioration of oxidative stress and modulation of antioxidative system. In conclusion, PBTE administration ameliorated QCT-induced nephrotoxicity by maintaining DNA's double-helix architecture and mitigating oxidative stress.
Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 11/2011; 50(2):147-54. · 2.99 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Quercetin, one of the most widely distributed flavonoids in plants, possesses strong free radical scavenging ability and potent hepatoprotective effects. However, the protective effect and mechanism of quercetin on ethanol-induced oxidative damage in hepatocytes remain unclear. In this study, primary rat hepatocytes were incubated with ethanol and quercetin in the presence or absence of ZnPP 9, an antagonist of HO-1 induction. The ethanol-induced hepatotoxicity was found to be greatly diminished by pre-treatment of quercetin and this hepatoprotective effect could be partly blocked by ZnPP 9. This study also showed that quercetin significantly stimulated HO-1 expression at both mRNA and protein levels, then subsequently induced HO-1 activity. To further study the signaling pathways underlying quercetin-induced HO-1 up-regulation, HO-1 expression and activity in cytosolic microsomal fractions and Nrf2 expression in nuclear fractions were analyzed following quercetin or/and MAPK inhibitor(s) as well as PI3K inhibitor incubation for primary rat hepatocytes. These results indicated that ERK was required to induce HO-1 expression in rat hepatocytes. In summary, these data suggested that quercetin attenuates ethanol-induced oxidative stress through a pathway which involves ERK activation and HO-1 upregulation.
Toxicology in Vitro 10/2011; 26(1):74-80. · 2.78 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Mice were subcutaneously injected with d-galactose (D-gal, 150 mg/kg per day) for 6 weeks and were administered high molecular weight persimmon condensed tannin (HMWPT) simultaneously. After 6 weeks of treatment, the animal behavior was observed in the open field test and water maze test, and the morphology of hippocampus and skin were checked. Meanwhile, the activities of antioxidant enzymes, the levels of non-enzymatic antioxidants, as well as malondialdehyde (MDA) were evaluated. The results indicated that HMWPT markedly inhibited the d-gal induced learning and memory impairment in both open field test and Morris water maze. Biochemical examination revealed that HMWPT significantly increased the decreased activities of superoxide dismutase (SOD), catalase (CAT), elevated the lowered total anti-oxidation capability (T-AOC), glutathione (GSH) and hydroxyproline (Hyp) contents (p<0.01 or p<0.05), and decreased the raised monoamine oxidase (MAO), total cholinesterase (TChE) activities and MDA level (p<0.01) in serum, liver or brain of aging mice induced by d-gal in a dose-dependent fashion. Furthermore, HMWPT significantly and (p<0.01) attenuated the d-gal induced number decrease, neuronal degeneration and karyopycnosis in cells in the hippocampus and decrease of thickness of skin epidermis and dermis.
Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 08/2011; 49(8):1728-36. · 2.99 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Quinocetone (3-methyl-2-quinoxalinbenzenevinylketo-1,4-dioxide, QCT), a new feed antibacterial agent of quinoxaline-1,4-dioxides family, has been used as an animal growth promoter. However, few data about its potential toxicity in vivo were available. In this study, genotoxicity of QCT and the relationship with oxidative stress were investigated. Balb/c mice with both sexes were administrated with QCT (12000, 6000 and 3000 mg/kg/bw, respectively) by gavage acutely. DNA damage, generation of reactive oxygen species (ROS) and activity of antioxidative system (total antioxidative capacity, glutathione, glutathione peroxidase, superoxide dismutase and catalase) in liver and kidney were determined. Moreover, Pu-erh black tea extract (BTE) was co-administrated with QCT to evaluate its protective effect against QCT-induced genotoxicity. The DNA damage was observed in all the groups treated with single QCT except the liver with dose of 3000 mg/kg/bw. ROS was accumulated and antioxidative system was suppressed both in liver and kidney. However, the DNA damage, as well as the ROS, was decreased, while the activity of antioxidative system was increased in mice after co-administration of QCT and BTE. These data demonstrate that oxidative stress mediated the genotoxicity induced by QCT in vivo. Furthermore, this oxidative DNA damage can be attenuated by pre-supplementation of BTE.
Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 02/2011; 49(2):477-84. · 2.99 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The major purpose of this study was to determine the effect of procyanidins extracted from the lotus seedpod (LSPC) on the nitric oxide (NO) system in the hippocampus and cerebral cortex in cognitively impaired aged rats. Using the Morris water maze, aged-unimpaired (AU) and aged-impaired (AI) rats were chosen from aged rats. All aged rats exhibited elevated inducible nitric oxide synthase (iNOS) activities and decreased neuronal nitric oxide synthase (nNOS) activities in the both brain regions. The changes were more pronounced in the brain of AI rats, especially in the hippocampus. Furthermore, AI rats greatly lowed the percentage of change of hippocampal nNOS activity in the presence of protein kinase inhibitors or phosphatase inhibitor, which meant that AI animals existed in a hardly modified nNOS dephosphorylated state in hippocampus. LSPC supplementation [50, 100 mg/kg of body weight (BW), per os (p.o.)] for 7 weeks significantly decreased iNOS activities and improved hippocampal nNOS phosphorylation status in AI animals. These results suggested that changes in the NO system may involve in the ameliorative effects of LSPC on cognitive deficits in AI animals.
Rejuvenation Research 02/2011; 14(1):33-43. · 3.83 Impact Factor
