Hepatic Antioxidant System Research Articles

Oxidative stress and mitochondrial uncoupling protein 2 expression in hepatic steatosis induced by exposure to xenobiotic DDE and high fat diet in male Wistar rats.

Oxidative stress plays a key role in steatohepatitis induced by both xenobiotic agents and high fat diet (HFD). The present study aimed to evaluate hepatic oxidative stress and anti-oxidant systems response in rats exposed to HFD and/or non-toxic dose of dichlorodiphenyldichloroethylene (DDE), the first metabolite of dichlorodiphenyltrichloroethane. Groups of 8 rats were so treated for 4 weeks: 1- standard diet (N group); 2- standard diet plus DDE (10 mg/kg b.w.) (N+DDE group); 3- HFD (D group); 4- HFD plus DDE (D+DDE group). Oxidative stress was analyzed by determining malondialdehyde as lipid peroxidation product, while the anti-oxidant systems were evaluating by measuring the levels of the principal cytosolic and mitochondrial antioxidant proteins and enzymes, namely superoxide dismutase 1 and 2 (SOD1, SOD2), glutathione peroxidase 1 (GPx1) and uncoupling protein 2 (UCP2) involved in the control of hepatic reactive oxygens species (ROS) accumulation. The results showed malondialdehyde accumulation in livers of all groups, confirming the pro-oxidant effects of both HFD and DDE, but with a greater effect of DDE in absence of HFD. In addition, we found different levels of the analyzed anti-oxidant systems in the different groups. DDE mainly induced UCP2 and SOD2, while HFD mainly induced GPx1. Noteworthy, in the condition of simultaneous exposure to DDE and HFD, the anti-oxidant response was more similar to the one induced by HFD than to the response induced by DDE. Present findings confirmed that both HFD and xenobiotic exposure induced hepatic oxidative stress and showed that the anti-oxidant defense response was not the same in the diverse groups, suggesting that UCP2 induction could be an adaptive response to limit excessive ROS damage, mainly in condition of xenobiotic exposure.

Luteolin Targets the Toll-Like Receptor Signaling Pathway in Prevention of Hepatic and Adipocyte Fibrosis and Insulin Resistance in Diet-Induced Obese Mice.

This study was to investigate the protective role of luteolin on inflammation-mediated metabolic diseases, focusing on the role of luteolin in the modulation of the Toll-like receptor (TLR) signaling pathway. C57BL/6J mice were fed a normal, high-fat, or high-fat + 0.005% (w/w) luteolin diet for 16 weeks. Luteolin improved chronic low-grade inflammation by modulating the TLR signaling pathway, resulting in reduced pro-inflammatory cytokines and macrophage accumulation. A positive relationship was detected between gene expressions of Tlr5, Map2k7, Mapk12, Mapk13, and Mapk9 and lipogenesis in epididymal white adipose tissue (eWAT) of luteolin-treated mice, which was linked to attenuation of hepatic lipotoxicity by increasing free fatty acid (FFA) flux to the WAT. Luteolin prevented fibrosis by decreasing extracellular matrix accumulation and cathepsin gene expressions, while enhancing the hepatic antioxidant system. Emr1 and Ccl7, important markers inducing low-grade inflammation, were affected by advanced age and greater body weight, which were normalized by luteolin treatment. Luteolin improved insulin resistance by normalizing pancreatic islet dysfunction and differentially modulating the plasma glucagon-like peptide-1 and gastric inhibitory polypeptide levels. Our results suggest that luteolin ameliorates diet-induced obesity and its comorbidities. Overall, this study provides novel insights into the effect of luteolin on the links among adiposopathy, insulin resistance, hepatic steatosis, and fibrosis.

Discrepant effects of α-endosulfan, β-endosulfan, and endosulfan sulfate on oxidative stress and energy metabolism in the livers and kidneys of mice

Endosulfan, an organochloride pesticide, has been used for many commercial purposes. Endosulfan is composed of two isomers, α-endosulfan and β-endosulfan. In biological and soil systems, endosulfan is metabolized into endosulfan sulfate. In this study, the different toxicological effects of α-endosulfan, β-endosulfan, and endosulfan sulfate on the livers and kidneys of mice were comprehensively investigated. The results demonstrated that both endosulfan isomers and endosulfan sulfate disturbed the hepatic and renal antioxidant systems. Furthermore, 1H NMR metabolomics analysis revealed that endogenous metabolites involved in oxidative stress and energy metabolism were altered after exposure to these compounds. In the liver, the changes in hepatic endogenous metabolites and the induction of hepatic CYP450 mRNA isoforms were similar among mice treated with the three compounds, and the sulfate metabolite was the exclusive exogenous compound detected. Therefore, the metabolism of α- and β-endosulfan to endosulfan sulfate is likely the main cause of toxicological effects in the livers of mice. However, in kidneys, the changes in the metabolome and in CYP450 mRNA expression induced by α-endosulfan and β-endosulfan were stereoselective. Additionally, endosulfan sulfate, which induced a significant increase of renal Cyp3a11, showed a more robust disturbance of renal metabolites than either of the two isomers. These findings revealed that more attention should be given to the toxicological evaluation of endosulfan sulfate in the future.

Sub‐Chronic Exposure to Organic Arsenic Disrupts Hepatic Energy Metabolism and Antioxidant System

Arsenic is a ubiquitous toxicant, having a wide range of toxic effects on different systems in the body. To investigate the sub‐chronic effects of exposure to low doses of cacodylic acid (organic arsenic) on some enzymes of energy metabolism and antioxidant system in the liver, rats were exposed to cacodylic acid (20 ppm and 40 ppm) in their drinking water for ten weeks. Control animals received distilled water. Activities of catalase (CAT), glutathione peroxidase (GPx), glutathione‐S‐transferase (GST), superoxide dismutase (SOD), NAD glycohydrolase (NADase), xanthine oxidase (XO) and lactate dehydrogenase (LDH) and the levels of nitric oxide (NO), reduced glutathione (GSH) and lipid peroxidation (MDA) were determined in hepatic cytosol while malate dehydrogenase (MDH) and respiratory chain enzymes (complexes I, II and IV) activities were determined in the mitochondrial fraction. There were significant (p<0.05) decreases in the level of GSH and activities of NADase, MDH and complex IV in the exposed groups compared with the control. In the 20 ppm group, activity of hepatic SOD and level of NO increased by 419% and 142% respectively. A hormetic response was observed in the activity of GST. The activities of complexes I and II decreased as a result of exposure to cacodylic acid, these decreases were dose‐dependent. Our findings indicate that disruption of energy metabolism and antioxidant system by cacodylic acid might play a role in the pathogenesis of its hepatotoxicity.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

A novel therapeutics agent: antioxidant effects of hydroxylfasudil on rat kidney and liver tissues in a protamine sulphate-induced cystitis rat model; preliminary results

Cystitis is defined as an inflammation of the bladder caused by a bacterial infection, and it can be dangerous and painful when it spreads through the internal organs. In this study, antioxidant effects of hydroxylfasudil (HF) at the enzymatic and molecular level on kidney and liver tissues in cystitis rat model, which is caused by inflammation of the rat bladder with a protamine sulphate (PS), was examined. Quantitative changes of reduced glutathione (GSH) and lipid peroxidation (LPO) levels, which are a marker for oxidative stress, were determined in rat kidney and liver tissues for each groups. And then molecular and biochemical impact of HF treatment on antioxidant enzymes including superoxide dismutase (SOD) and catalase (CAT) in cystitis model were studied. The results suggest that HF could be beneficial to the renal and hepatic antioxidant system. Thus, HF might be used as a novel therapeutics agent to eliminate interstitial cystitis.

Adaptogenic potential of royal jelly in liver of rats exposed to chronic stress.

Restraint and cold stress increase both corticosterone and glycemia, which lead to oxidative damages in hepatic tissue. This study assessed the effect of royal jelly (RJ) supplementation on the corticosterone level, glycemia, plasma enzymes and hepatic antioxidant system in restraint and cold stressed rats. Wistar rats were allocated into no-stress, stress, no-stress supplemented with RJ and stress supplemented with RJ groups. Initially, RJ (200mg/Kg) was administered for fourteen days and stressed groups were submitted to chronic stress from the seventh day. The results showed that RJ supplementation decreases corticosterone levels and improves glycemia control after stress induction. RJ supplementation also decreased the body weight, AST, ALP and GGT. Moreover, RJ improved total antioxidant capacity, SOD activity and reduced GSH, GR and lipoperoxidation in the liver. Thus, RJ supplementation reestablished the corticosterone levels and the hepatic antioxidant system in stressed rats, indicating an adaptogenic and hepatoprotective potential of RJ.

Co-exposure to titanium dioxide nanoparticles (NpTiO2) and lead at environmentally relevant concentrations in the Neotropical fish species Hoplias intermedius.

Growing production and utilization of titanium dioxide nanoparticles (NpTiO2) invariably lead to their accumulation in oceans, rivers and other water bodies, thus increasing the risk to the welfare of this ecosystem. The progressive launch of these nanoparticles in the environment has been accompanied by concern in understanding the dynamics and the toxic effect of these xenobiotic in different ecosystems, either on their own or in tandem with different contaminants (such as organic compounds and heavy metals), possibly altering their toxicity. Nevertheless, it remains unknown if these combined effects may induce damage in freshwater organisms. Therefore, this study aimed to analyze the consequences caused by NpTiO2, after a waterborne exposure of 96 h to a Neotropical fish species Hoplias intermedius, as well as after a co-exposure with lead, whose effects for fish have already been well described in the literature. The characterization of NpTiO2 stock suspension was carried out in order to provide additional information and revealed a stable colloidal suspension. As a result, NpTiO2 showed some genotoxic effects which were observed by comet assay in gill, kidney and brain cells. Also, the activity of brain acetylcholinesterase (AChE) has not changed, but the activity of muscle AChE decreased in the group exposed only to PbII. Regarding the hepatic antioxidant system, catalase (CAT) did not show any change in its activity, whereas that of superoxide dismutase (SOD) intensified in the groups submitted only to PbII and NpTiO2 alone. As for lipid peroxidation, there was a decrease in the group exposed to the NpTiO2 alone and to the co-exposed group (NpTiO2+PbII). As far as metallothionein is concerned, its concentration rose for the co-exposed group (NpTiO2+PbII) and for the group exposed to PbII alone. Overall, we may conclude that NpTiO2 alone caused DNA damage to vital tissues. Also, some impairment related to the antioxidant mechanism was described but it is probably not related to the DNA damage observed, suggesting that the genotoxic effect observed may be due to a different mechanism instead of ROS production.

Serine alleviates oxidative stress via supporting glutathione synthesis and methionine cycle in mice.

Serine lies at the central node linking biosynthetic flux from glycolysis to glutathione synthesis and one-carbon metabolic cycle which are closely related to antioxidant capacity. The present study was conducted to determine the effects of serine supplementation on oxidative stress and its relative mechanisms. Diquat treatment was performed to induce oxidative stress in mice and primary hepatocytes. The results showed that hepatic glutathione anti-oxidant systems were impaired and reactive oxygen species and homocysteine were increased in diquat-induced mice and hepatocytes, while such disadvantageous changes were diminished by serine supplementation both in vivo and in vitro. However, when cystathionine β-synthase expression was inhibited by interference RNA in hepatocytes, the effects of serine supplementation on the improvement of glutathione synthesis and the alleviation of oxidative stress were diminished. Moreover, when hepatocytes were treated with cycloleucine, an inhibitor of methionine adenosyltransferase, the effects of serine supplementation on the improvement of methionine cycle and the alleviation of DNA hypomethylation and oxidative stress were also diminished. Our results indicated that serine supplementation alleviated oxidative stress via supporting glutathione synthesis and methionine cycle, mostly by condensing with homocysteine to synthesize cysteine and providing one-carbon units for homocysteine remethylation.

Melaleuca alternifolia essential oil prevents oxidative stress and ameliorates the antioxidant system in the liver of silver catfish (Rhamdia quelen) naturally infected with Ichthyophthirius multifiliis

Oxidative stress has been linked to a pathological mechanism that contributes to the initiation and progression of hepatic injury during Ichthyophthirius multifiliis infection. Thus, natural compounds with antioxidant and free radical scavenger properties, such as the Melaleuca alternifolia essential oil (TTO), might help to prevent or reduce hepatic damage. Thus, the aim of this study was to investigate whether TTO is capable of preventing or reducing hepatic oxidative damage in silver catfish naturally infected with I. multifiliis. After a TTO bath treatment of 1h/day for 4days, the number of trophonts on the skin of catfish was reduced by 94.87% compared to the control group. Hepatic samples from fish infected by I. multifiliis showed increased thiobarbituric acid reactive substances (TBARS) and protein carbonylation levels, while catalase (CAT) activity decreased compared to uninfected and untreated animals. Moreover, the histopathology analyses demonstrated the presence of necrosis, nuclear lateralization and cariorrexis, as well as swelling and vacuolization of cytoplasm. Treatment with TTO reduced hepatic TBARS and protein carbonylation levels and ameliorated the antioxidant system of infected fish, as well as preserve the hepatocytes morphology, but not prevented the occurrence of necrosis. Based on our findings, we propose that TTO is an alternative therapeutic option for silver catfish infected with I. multifiliis. Moreover, TTO treatment is a useful approach for avoiding or minimizing the hepatic oxidative stress caused by I. multifiliis, thus improving the hepatic antioxidant system.

Evidence for Chlordecone-Stimulated Oxidative Stress in Different Tissues of the Cichlid Fish, Pseudetroplus Maculatus (Bloch, 1795)

Abstract The present study was designed to assess the effect of chlordecone on the stimulation of oxidative stress in gill, liver and brain tissues of the cichlid fish, Pseudetroplus maculatus. Fishes were exposed to chlordecone at two sublethal concentrations, 3.5 and 7 μg/L, for 24, 72 and 96 h, maintaining ten animals in each group. Chlordecone treatment did not alter the body weight of the animal. However, significant increase in the secretion of mucous and decrease in the weights of gill, brain and hepatosomatic index were observed at 7 μg/L of chlordecone treatment only after 96 h. Gill tissue showed significant increase in the activities of superoxide dismutase, catalase and glutathione reductase along with elevated levels of hydrogen peroxide and lipid peroxidation in concentration and timedependent manner. This could be the defensive mechanism of gill tissue to escape the toxic effects of chlordecone. In the liver tissue, superoxide dismutase activity was increased by 39% at 3.5 μg/L and by 73% at 7 μg/L of chlordecone treatment. Activities of catalase and glutathione reductase were decreased 3 to 9 times at 3.5 and 7 μg/L concentrations, respectively, with concomitant increase in hydrogen peroxide generation (17 to 28 times) and lipid peroxidation (3 to 7 times) at the end of 96 h, which reveals the failure of hepatic antioxidant system to prevent free radical generation owing to chlordecone exposure. Activities of all antioxidant enzymes in the brain were inhibited by 29 to 80% along with the induction of hydrogen peroxide (13 to 20 times) and lipid peroxidation (6 to 11 times), thereby indicating imbalance in the antioxidant status. Activities of gill and liver marker enzyme - alkaline phosphatase - and acetylcholinesterase in brain were decreased. Therefore, imbalance in the antioxidant defence system as a result of chlordecone toxicity could lead to susceptible oxidative stress in various tissues of the fish.

Effects of coenzyme Q10 on the antioxidant system in SD rats exposed to lipopolysaccharide-induced toxicity

The study was performed to see the effects of coenzyme Q10 (CoQ10) on blood biochemical components and hepatic antioxidant system in rats exposed to lipopolysaccharide (LPS)-induced toxicity. A total of 24 rats were allocated to four groups: control (CON), 100 mg/kg BW of LPS (LPS), 100 mg of CoQ10/kg BW with LPS (LCQI) and 300 mg of CoQ10/kg BW with LPS (LCQII). The LPS and LCQI groups showed a significant (P<0.05) increase in the relative spleen weight compared with the CON group without affecting body and liver weights. The blood alanine aminotransferase (ALT) level in the LPS group was significantly (P<0.05) greater than that in the CON group, while supplementation with 100 or 300 mg CoQ10 to rats injected with LPS normalized the ALT level in the CON group. In antioxidant systems, the LPS group showed a significantly (P<0.05) higher mRNA and activity of superoxide dismutase (SOD) than the CON group. The supplementation with CoQ10 to the LPS-treated group normalized the level of SOD, which was comparable to the level of the CON group. Both the mRNA expression and activity of glutathione peroxidase in the LCQI and LCQII groups were higher (P<0.05) than that of the LPS group. However, administration of LPS or CoQ10 unaffected the level of catalase and total antioxidant power. The level of lipid peroxidation in the LCQII group was lower (P<0.05) than that in the LPS group. In conclusion, CoQ10 exerted its favorable effect against liver damage by modulation of antioxidant enzymes in LPS treated rats.

Активність ферментативної ланки антиоксидантної системи в печінці при введенні бісфенолу а за відсутності запасів ретиноїдів

Активність ферментативної ланки антиоксидантної системи в печінці при введенні бісфенолу а за відсутності запасів ретиноїдів

Imbalance of the antioxidative system by plumbagin and Plumbago indica L. extract induces hepatotoxicity in mice.

Background/Aim:Plumbago indica (PI) L. and its active constituent, plumbagin, has been traditionally claimed for several pharmacological activities; however, there is little information regarding their toxicity. The present study aims to examine the effects of plumbagin and PI extract (PI) on hepatic histomorphology and antioxidative system in mice.Materials and Methods:Adult male intelligent character recognition mice were intragastrically administered plumbagin (1, 5, and 15 mg/kg/day) or PI (20, 200, and 1,000 mg/kg/day) consecutively for 14 days. Hepatic histomorphology was examined. Plasma alanine transaminase (ALT) and aspartate transaminase (AST) levels, hepatic lipid peroxidation, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities, and the ratio of reduced to oxidized glutathione (GSH/GSSG) were determined.Results:Plumbagin and PI concentration-dependently induced hepatic injury based on histopathological changes via imbalance of antioxidative system. Plumbagin and PI significantly increased plasma ALT and AST levels, hepatic lipid peroxidation, and GPx activity but significantly decreased hepatic SOD and CAT activities. The GSH/GSSG ratio was significantly reduced by plumbagin.Conclusion:Plumbagin and PI caused hepatotoxic effects in the mice by unbalancing of the redox defense system. Therefore, plumbagin and PI-containing supplements should be used cautiously, especially when consumed in high quantities or for long periods.

The ameliorating effects of vitamin E on hepatic antioxidant system and xenobiotic-metabolizing enzymes in fenvalerate-exposed iodine-deficient rats

This study investigated the effects of vitamin E (VE) on hepatic antioxidant system and drug-metabolizing enzymes in fenvalerate (FEN)-exposed iodine-deficient (ID) Wistar rats. ID was produced by perchlorate containing drinking water. VE was introduced by a loading dose of 100 mg/kg/d, i.g. for the first three days in the last week of feeding period; then with a single maintenance dose of 40 mg/kg on the 4th day. During last week, FEN groups (F) received 100 mg/kg/d, i.p. FEN. VE alone did not significantly affect thyroid hormones and antioxidant parameters; however, significantly increased total cytochrome P450 (38%) and cytochrome b5 levels (36%). In all ID groups, plasma thyroid-stimulating hormone (TSH) levels increased markedly, but remained at control level in vitamin E plus FEN receiving iodine-deficient group (IDVF) group. Glutathione peroxidase activity showed marked increases in F (19%) and FEN-exposed iodine-deficient group (IDF, 48%) groups. FEN treatment significantly increased total cytochrome P450 (28%) and thiobarbituric acid reactive substance levels (36%), as well as 7-ethoxyresorufin O-deethylase (120%), 7-penthoxyresorufin O-deethylase (139%) and glutathione S-transferase (15%) activities and decreased total glutathione concentrations (28%) versus control. Overall results suggest that vitamin E has ameliorating effects on the measured parameters in ID and/or FEN exposure.

Alteration of hepatic anti-oxidant systems by 4-nonylphenol, a metabolite of alkylphenol polyethoxylate detergents, in Far Eastern catfish Silurus asotus.

ObjectivesThis study aimed to estimate the effects of 4-nonylphenol (NP), a ubiquitously present surfactant in aquatic environments, on the anti-oxidant systems of the liver in the Far Eastern catfish Silurus asotus.MethodsChanges in biochemical parameters involved in glutathione (GSH)-related and other anti-oxidant systems were analyzed following 4 weeks of 4-NP administration (0.1 and 1.0 mg/kg diet) via a formulated diet to catfish.Results4-NP exposure induced an elevation in hepatic lipid peroxide levels and an accompanying decrease in reduced state GSH after 2 weeks, suggesting pro-oxidant effects of the chemical in catfish. This oxidative stress was associated with an inhibition of the GSH-utilizing enzyme glutathione peroxidase at the same time point. This inhibition was restored after 4 weeks. The activities of other anti-oxidant enzymes, i.e., glutathione reductase, superoxide dismutase and catalase were increased after 4 weeks. These enzyme increases occurred more strongly at the higher 4-NP concentration (1.0 mg/kg diet).Conclusions4-NP given to catfish at 0.1 to 1.0 mg/kg diet, concentrations relevant to environmental levels, depletes the endogenous anti-oxidant molecule GSH and temporarily inhibits GSH-related anti-oxidant enzymes. Such declines in anti-oxidant capacity and elevated oxidative stress seem to be compensated eventually by subsequent activation of various anti-oxidant enzyme systems.

P1108 : Elevated acetaldehyde levels are detrimental to the hepatic antioxidant system

P1108 : Elevated acetaldehyde levels are detrimental to the hepatic antioxidant system

Effect of N-(D-Ribopyranosyl)taurine Sodium Salt Supplementation on the Hepatic Antioxidant System in Rat Models of Diet-Induced Obesity and Taurine Deficiency.

N-(d-Ribopyranosyl)taurine sodium salt (T-Rib) is a newly synthesized compound containing taurine and ribose. This study was conducted to investigate the effect of T-Rib supplementation on the hepatic antioxidant system in rat models of diet-induced obesity and taurine deficiency. To induce taurine deficiency, β-alanine was administered by dissolving it in drinking water (3 % w/v). Fifty-six male Sprague-Dawley rats (4-week-old) were randomly divided into the following seven groups with eight rats in each group for 6 weeks: N group, normal diet; HF group, high-fat diet; HFT group, high-fat diet and 4 mmol/kg/day taurine; HFA group, high-fat diet and β-alanine; HFR2 group, high-fat diet, β-alanine, and 2 mmol/kg/day T-Rib; HFR4 group, high-fat diet, β-alanine, and 4 mmol/kg/day T-Rib; and HFR6 group, high-fat diet, β-alanine, and 6 mmol/kg/day T-Rib. Taurine and T-Rib were orally administered to the HFT and HFR groups, respectively. To investigate the effect of T-Rib on the hepatic antioxidant system, serum glutamate oxaloacetate transaminase (GOT) and glutamate pyruvic transaminase (GPT) activities were analyzed. In addition, thiobarbituric acid reactive substance (TBARS) content, glutathione (GSH) content and glutathione peroxidase (GPx) activity in the liver were analyzed. Serum GOT levels, hepatic TBARS content, and GPx activities in the HFT and HFR groups significantly improved compared to the corresponding values in the HF and HFA groups. These results suggest that supplementation with T-Rib as well as with taurine could be beneficial to the hepatic antioxidant system in rat models of diet-induced obesity and taurine deficiency. Further study is needed to investigate the mechanism of T-Rib action.

N-(β- D-Xylopyranosyl)taurine Sodium Salt Supplementation Has Beneficial Effect on the Hepatic Antioxidant System of Rats Fed a High-Fat Diet and β-Alanine.

N-(β-d-Xylopyranosyl)taurine sodium salt (T-Xyl) was newly synthesized from taurine and xylose. We hypothesized that T-Xyl would have positive effects on the hepatic antioxidant system of rats fed a high-fat diet and β-alanine. β-Alanine was administered for induction of taurine depletion by dissolving in feed water (3 % w/v). Fifty-six male Sprague-Dawley rats (4-week-old) were randomly divided into seven groups with eight rats per group and fed an experimental diet for 6 weeks (N, normal diet; HF, high-fat diet; HFT, high-fat diet + 4 mmol/kg/day taurine; HFA, high-fat diet + 3 % β-alanine; and HFTX 2,4,6, high-fat diet + 3 % β-alanine + 2, 4, 6 mmol/kg/ day T-Xyl). To investigate the effect of T-Xyl on the hepatic antioxidant system, we examined the activities of glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) in serum, hepatic thiobarbituric acid reactive substances (TBARS) and glutathione (GSH) content, and glutathione peroxidase (GPx) activity. In addition, we evaluated the histology of hepatocytes. The activity of GPT in serum was significantly lower in the HFT and HFTX groups than in the HF group (p < 0.05). TBARS content increased following administration of the HF diet, but significantly decreased upon administration of taurine and T-Xyl (p < 0.05). GPx activity was significantly higher in the HFTX4 and HFTX6 groups than in the HFA group. These results suggest that T-Xyl supplementation in rats fed a high-fat diet and β-alanine seems to have beneficial effects on the hepatic antioxidant system.

Chemical composition of Pleurotus eryngii polysaccharides and their inhibitory effects on high-fructose diet-induced insulin resistance and oxidative stress in mice.

High intake of dietary fructose exerts a number of adverse metabolic effects. The present study investigates the preventive effects of Pleurotus eryngii polysaccharides (PEP), which showed powerful antioxidant activity in vitro, on insulin resistance and oxidative stress in mice fed a high-fructose diet. PEP was identified by HPLC as the heteropolysaccharides with d-glucose (62.8%, mol%), d-galactose (24.4%) and d-mannose (9.8%) being the main component monosaccharides. Mice fed 20% fructose in drinking water for 6 weeks significantly displayed hyperglycemia, hyperinsulinemia, dyslipidemia and liver oxidative stress with impaired insulin sensitivity (p < 0.05). The administration of PEP at 400 and 800 mg kg(-1) bw significantly reduced the fasting serum glucose and insulin concentrations and lipid deposition in HF-fed mice, and caused the reduction of liver lipid peroxidation and the elevation of the hepatic antioxidant system. The histopathology of the liver by conventional H&E and oil red O staining confirmed the liver steatosis induced by a HF diet and the hepatoprotective effect of PEP. These results suggest that Pleurotus eryngii is a potential source of polysaccharides, and might be regarded as a novel preventive and therapeutic product for the mitigation of insulin resistance, oxidative stress and liver dysfunction.

Stimulation of gene expression and activity of antioxidant related enzyme in Sprague Dawley rat kidney induced by long-term iron toxicity

The trace elements such as iron are vital for various enzyme activities and for other cellular proteins, but iron toxicity causes the production of reactive oxygen species (ROS) that causes alterations in morphology and function of the nephron. The present study was designed to determine the effect of long-term iron overload on the renal antioxidant system and to determine any possible correlation between enzymatic and molecular levels. Our data showed that reduced glutathione (GSH) levels, which is a marker for oxidative stress, strikingly decreased with a long-term iron overload in rat kidney. While renal mRNA levels of glucose 6-phosphate dehydrogenase (G6pd), 6-phosphogluconate dehydrogenase (6pgd) and glutathione peroxidase (Gpx) were significantly affected in the presence of ferric iron, no changes were seen for glutathione reductase (Gsr) and glutathione S-transferases (Gst). While the iron affected the enzymatic activity of G6PD, GSR, GST, and GPX, it had no significant effect on 6PGD activity in the rat kidney. In conclusion, we reported here that the gene expression of G6pd, 6pgd, Gsr, Gpx, and Gst did not correlate to enzyme activity, and the actual effect of long-term iron overload on renal antioxidant system is observed at protein level. Furthermore, the influence of iron on the renal antioxidant system is different from its effect on the hepatic antioxidant system.