Hepatic Glutathione Reductase Research Articles

Antioxidant and protective effect of inulin and catechin grafted inulin against CCl4-induced liver injury

In this study, the antioxidant activity and hepatoprotective effect of inulin and catechin grafted inulin (catechin-g-inulin) against carbon tetrachloride (CCl4)-induced acute liver injury were investigated. Results showed that both inulin and catechin-g-inulin had moderate scavenging activity on superoxide radical, hydroxyl radical and H2O2, as well as lipid peroxidation inhibition effect. The antioxidant activity decreased in the order of Vc>catechin>catechin-g-inulin>inulin. Administration of inulin and catechin-g-inulin could significantly reduce the elevated levels of serum aspartate transaminase, alanine transaminase and alkaline phosphatase as compared to CCl4 treatment group. Moreover, inulin and catechin-g-inulin significantly increased the levels of hepatic superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione and total antioxidant capacity, whereas markedly decreased the malondialdehyde level when compared with CCl4 treatment group. Notably, catechin-g-inulin showed higher hepatoprotective effect than inulin. In addition, the hepatoprotective effect of catechin-g-inulin was comparable to positive standard of silymarin. Our results suggested that catechin-g-inulin had potent antioxidant activity and potential protective effect against CCl4-induced acute liver injury.

Antioxidant effect of grapevine leaf extract on the oxidative stress induced by a high-fat diet in rats

This study was conducted to investigate the effect of grapevine leaf extract (GLE) on the oxidative stress of rats fed a high-fat diet. Rats were divided into six groups: a normal diet with 0% (NC), 1.0% (NG1.0), and 1.5% GLE (NG1.5); and a high-fat diet with 0% (HFC), 1.0% (HFG1.0), and 1.5% GLE (HFG1.5). Treatment with GLE to the high-fat diet reduced lipid peroxide concentrations in plasma and liver compared to those of HFC rats. Total glutathione and GSH/GSSG of the groups with GLE were higher than those of untreated groups. Hepatic glutathione peroxidase, glutathione-S-transferase, and glutathione reductase activities along with catalase and glutathione peroxidase activities in erythrocytes increased after GLE treatment to high-fat diet compared with HFC rats. Hepatic retinol and tocopherol increased in HFG1.5 group compared to those of HFC group. These results indicate that GLE can protect against oxidative stress induced by a high-fat diet in rats.

Impact of environmental concentrations of beta-cypermethrin on the antioxidant system in the brain and liver of zebrafish (Danio rerio)

Beta-cypermethrin (beta-CYP) is a widely used pyrethroid pesticide, the extensive application of which may potentially cause damage to non-target organisms. To investigate the effect of beta-CYP on the antioxidant system of aquatic animals, adult zebrafish were exposed to environmentally relevant dosages (0.01, 0.1 and 1.0 μg/L) of beta-CYP. The activities of four antioxidant enzymes in zebrafish liver and brain tissue were tested after 7, 15 and 30 days of exposure. Our results showed that exposure of beta-CYP could induce different levels of increase in hepatic superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) and glutathione peroxidase (GPx) activities at 7 and 15 days post exposure (dpe), but caused apparent inhibition of hepatic SOD, GR and GPx activities at 30 dpe. Unlike in liver tissue, SOD and CAT activities in zebrafish brain did not show any apparent response to beta-CYP during the whole treatment period. In addition, increased brain GPx activities were observed at 7 and 30 dpe.

Schisandra Chinensis Baillon regulates the gene expression of phase II antioxidant/detoxifying enzymes in hepatic damage induced rats.

BACKGROUND/OBJECTIVESThis study investigated the antioxidant activities and hepatoprotective effects of Schisandra chinensis Baillon extract (SCE) against tert-butyl hydroperoxide (t-BHP)-induced oxidative hepatic damage in rats.MATERIALS/METHODSSprague-Dawley (SD) rats were pretreated with SCE (300, 600, and 1,200 mg/kg BW) or saline once daily for 14 consecutive days. On day 14, each animal, except those belonging to the normal control group, were injected with t-BHP (0.8 mmol/kg BW/i.p.), and all of the rats were sacrificed 16 h after t-BHP injection.RESULTSAlthough no significant differences in AST and ALT levels were observed among the TC and SCE groups, the high-dose SCE group showed a decreasing tendency compared to the TC group. However, erythrocyte SOD activity showed a significant increase in the low-dose SCE group compared with the TC group. On the other hand, no significant differences in hepatic total glutathione (GSH) level, glutathione reductase (GR), and glutathione peroxidase (GSH-Px) activities were observed among the TC and SCE groups. Hepatic histopathological evaluation revealed that pretreatment with SCE resulted in reduced t-BHP-induced incidence of lesions, such as neutrophil infiltration, swelling of liver cells, and necrosis. In particular, treatment with a high dose of SCE resulted in induction of phase II antioxidant/detoxifying enzyme expression, such as glutathione S-transferase (GST) and glutamate-cysteine ligase catalytic subunit (GCLC).CONCLUSIONSBased on these results, we conclude that SCE exerts protective effects against t-BHP induced oxidative hepatic damage through the reduction of neutrophil infiltration, swelling of liver cells, and necrosis. In addition, SCE regulates the gene expression of phase II antioxidant/detoxifying enzymes independent of hepatic antioxidant enzyme activity.

Role of selenium and glutathione peroxidase on development, growth, and oxidative balance in rat offspring

Selenium (Se), an essential trace metal, is important in both growth and reproduction and is the constituent of different selenoproteins. The glutathione peroxidase (GPx) family is the most studied as it prevents oxidative stress. Liver oxidation is considered as another mechanism involved in low birth weight. Therefore, in order to ascertain whether GPx is related to the effects of Se on growth during gestation and lactation, three groups of rat pups were used: control, Se deficient (SD), and Se supplemented (SS). Morphological parameters and reproductive indices were evaluated. Hepatic Se levels were measured by graphite furnace atomic absorption while spectrophotometry was used for activity of antioxidant enzymes and oxidative stress markers in liver and western blotting for expression of hepatic GPx1 and GPx4. The SD diet increased mortality at birth; decreased viability and survival indices; and stunted growth, length, and liver development in offspring, thus decreasing hepatic Se levels, GPx, glutathione reductase, and catalase activities, while increasing superoxide dismutase activity and protein oxidation. The SS diet counteracted all the above results. GPx1 expression was heavily regulated by Se dietary intake; however, although Se dietary deficiency reduced GPx4 expression, this decrease was not as pronounced. Therefore, it can be concluded that Se dietary intake is intimately related to growth, length, and directly regulating GPx activity primarily via GPx1 and secondly to GPx4, thus affecting liver oxidation and development. These results suggest that if risk of uterine growth retardation is suspected, or if a neonate with low birth weight presents with signs of liver oxidation, it may be beneficial to know about Se status.

Confinement during field studies may jeopardize antioxidant and physiological responses of Nile tilapia to contaminants

This work evaluates the effects of caging, a known confinement stress, in Nile tilapia (Oreochromis niloticus) during an environmental study in Cubatão river, southern Brazil. Caging animals for 7 days, regardless of being at the reference or at a contaminated site, resulted in lower levels of antioxidant-related defenses (glutathione, glutathione S-transferase, glucose-6-phosphate dehydrogenase) in liver and physiological parameters (blood glucose and lactate) as compared with free-swimming animals. Higher hepatic glutathione reductase activity and elevated Hb content could be associated to contaminant exposure. In conclusion, the confinement stress in caged Nile tilapia biochemical and physiological disturbances, acting as a confounding factor in field studies.

Amelioration of ethanol-induced liver injury in rats by nanogold flakes

The purpose of this study was to investigate the protective effects of nanogold flakes against alcoholic liver disease. Six-week-old male Wistar rats were divided into 6 groups: C (control liquid diet), CLF (control liquid diet with gold flakes at 1.03 mg/kg body weight [BW]/day), CHF (control liquid diet with gold flakes at 5.15 mg/kg BW/day), E (ethanol liquid diet), ELF (ethanol liquid diet with gold flakes at 1.03 mg/kg BW/day), and EHF (ethanol liquid diet with gold flakes at 5.15 mg/kg BW/day). The liquid diets were prepared daily. Gold flakes were added to the ethanol 1 h before preparing the ethanol liquid diets, as an aging process. After 10 weeks, rats in group E showed significantly higher plasma aspartate transaminase (AST) and alanine transaminase (ALT) activities than those in group C. A significantly increased concentration of hepatic triglyceride (TG) was found in group E. Furthermore, higher hepatic glutathione reductase (GRD), superoxide dismutase (SOD), and catalase (CAT) activities together with higher tumor necrosis factor (TNF)-α concentration and higher hepatic cytochrome (CYP2E1) protein expression were also observed in group E. In contrast, the hepatic TG concentration in group EHF was significantly lower than that of group E. In addition, hepatic glutathione peroxidase (GPX), SOD, and CAT activities together with TNF-α concentration and hepatic CYP2E1 protein expression in group EHF were significantly lower than those in group E. We concluded that nanogold flakes might ameliorate alcohol-induced liver injury by maintaining the hepatic antioxidative status. In addition, nanogold flakes may reduce fat accumulation caused by chronic ethanol feeding via decreasing hepatic TNF-α.

Alleviation of Dimethylnitrosamine-Induced Liver Injury and Fibrosis by Supplementation of Anabasis articulata Extract in Rats.

Anabasis articulata (Forssk) Moq. (Chenopodiaceae) is an herb, grows in Egypt, and used in folk medicine to treat diabetes, fever, and kidney infections. The protective and therapeutic effects of the ethanol extract of A. articulata aerial parts were evaluated against dimethylnitrosamine (DMN)-induced liver fibrosis, compared with the standard drug, silymarin. Hepatic hydroxyproline content, serum transforming growth factor-β1 (TGF-β1), interleukin 10 (IL-10) and fructosamine were measured as liver fibrosis markers. Hepatic malondialdehyde (MDA), nitric oxide (NO), catalase (CAT), glutathione reductase (GR) and glutathione content (GSH) were measured as oxidant/antioxidant markers. Parallel histopathological investigations were also performed. Protective and therapeutic administration of A. articulata (100mg/kg daily for 4weeks), markedly prevented DMN-induced loss in body and liver weights. The extract significantly inhibited the elevation of hepatic hydroxyproline, NO and MDA (P<0.05), as well as serum fructosamine, and TGF-β1 (P<0.05) induced by DMN while it restored IL-10 to normal level in both protective and therapeutic groups. Furthermore, A. articulata prevented the depletion in CAT, GR, and GSH levels (P≤0.05). In addition, oral administration of A. articulata extract and silymarin to both protective and therapeutic groups reduced the increase in liver function enzyme activities; alanine and aspartate amintransferases, gamma-glutamyl transferase in addition to alkaline phosphatase, and caused significant increase in serum albumin concentration as compared to DMN group. These data corresponded closely with those obtained for the drug silymarin. Histopathological studies confirmed the biochemical data and revealed remarkable improvement in liver architecture. Thus, it could be concluded that, A. articulata extract exhibited in vivo hepatoprotective and therapeutic effects against DMN-induced liver injury and may act as a useful agent in controlling the progression of hepatic fibrosis through reduction of oxidative stress and improving liver function.

Prophylactic Effect of Resveratrol Against Ethinylestradiol-Induced Liver Cholestasis

Estrogens, and particularly glucuronides such as ethinylestradiol (EE), have been shown to cause cholestasis in animal studies, by reducing bile acid uptake by hepatocytes. The aim of the present article was to investigate anticholestatic activity of resveratrol (RES) against liver cholestasis induced by EE in adult female rats. The daily oral administration of the RES at a concentration of 25 mg/kg body weight for 15 days to rats treated with EE (100 μg/kg body weight for 5 days) resulted in a significant protection against EE-induced decrease in both serum cholesterol and bile acid levels as well as against an increase of serum bilirubin concentration. The treatment also resulted in a significant increase in hepatic superoxide dismutase, glutathione peroxidase, glutathione reductase, and catalase activities as well as hepatic protein-bound and nonprotein sulfhydryl groups. RES inhibited serum alkaline phosphatase, alanine aminotransferase, pi-glutathione-S-transferase, gamma-glutamyl transpeptidase, and alpha-glutathione-S-transferase activities, as well as reduced serum tumor necrosis factor-alpha, nitric oxide, and hepatic malondialdehyde as compared to EE-treated rats. The results clearly suggest that RES has a powerful prophylactic action in cholestasis induced by EE. Taken together, RES has potential as a preventive and therapeutic agent for cholestasis and deserves clinical trial in the near future as an adjuvant therapy in women treated with estrogen.

Protective effect of apigenin on mouse acute liver injury induced by acetaminophen is associated with increment of hepatic glutathione reductase activity

Apigenin, a natural plant flavone, has many beneficial effects, but there is no report about treatment of acetaminophen-induced liver injury. Our aim was to examine the protective effect of apigenin on acetaminophen-induced mouse acute liver injury and to investigate the potential mechanisms. A mouse model with acute liver injury was induced by intraperitoneally given acetaminophen 350 mg kg(-1) after oral administration of apigenin 100 and 200 mg kg(-1) for 7 days. The results showed that after treatment with apigenin, the levels of serum alanine aminotransferase and aspartate aminotransferase were gradually decreased, and the severity of liver injury was decreased. In particular, significant changes in liver necrosis were observed in the apigenin 200 mg kg(-1) group. Apigenin could gradually increase the hepatic glutathione reductase (GR) activity and reduced glutathione (GSH) content, and decrease the hepatic malondialdehyde content, but the activities of glutathione peroxidase and glutathione S-transferase in hepatic tissues between the model group and the apigenin-treated groups were not significantly different. It was concluded that apigenin could protect against acetaminophen-induced acute liver injury in mice, and the mechanisms might be associated with enhancing hepatic GSH content via increment of GR activity.

Japanese Butterbur (Petasites japonicus) Leaves Increase Hepatic Oxidative Stress in Male Rats

We investigated the adverse effects of Japanese butterbur leaves (Petasites japonicus, Compositae) in male F344/DuCrj rats. The rats were fed a control diet or a treatment diet containing 5% butterbur leaf powder for 4 weeks. No differences were observed in body weight gain, food intake or feed efficiency between treatments, but relative liver weight in the butterbur group was significantly higher than that of the control group. In addition, thiobarbituric acid reactive substances (TBARs) and glutathione levels in the serum and liver of the butterbur group were higher than those of the control group. Hepatic glutathione reductase and glutathione S-transferase activities and mRNA expression in the butterbur leaf group were higher than in the control group. Furthermore, hepatic cytochrome 2E1 mRNA expression was higher than in the control group. In vitro, an acetone extract of the butterbur leaf powder showed the strongest increase in TBARs level in a hepatic homogenate through 4 d. Our findings suggest that feeding 5% butterbur leaf powder to rats can cause adverse effects by increasing oxidative stress.

Effects of feeding corn naturally contaminated with aflatoxin B1 and B2 on hepatic functions of broilers

The purpose of this study was to evaluate the effects of feeding corn naturally contaminated with aflatoxin B(1) (AFB(1)) and aflatoxin B(2) (AFB(2)) on serum biochemical parameters, hepatic antioxidant enzyme activities, and pathological lesions of broilers. In total, 1,200 Cobb male broilers were randomly allocated into 5 treatments, with 8 replicates per treatment and 30 birds per replicate, in a 42-d experiment. The dietary treatments were as follows: control, 25, 50, 75, and 100% contaminated corn groups. Results showed that serum aspartate aminotransferase activity in the 75 and 100% contaminated groups were higher than that in the control group on d 21 (P < 0.05). Decreased content of hepatic total protein and increased activities of hepatic glutathione reductase and glutathione-S-transferase were observed as the percentage of contaminated corn increased (P < 0.05). The activity of superoxide dismutase and the content of hepatic malondialdehyde increased when the broilers were fed with more than 50% contaminated corn (P < 0.05). A reduction in glutathione peroxidase level was observed in the AFB(1)- and AFB(2)-contaminated groups on d 21 (P < 0.05). The average pathological lesion scores and apoptosis rate of liver cells increased as the concentration of dietary AFB(1) and AFB(2) increased. Ultrastructural changes were found in the livers of broilers fed 100% contaminated corn. In conclusion, diets containing AFB(1) and AFB(2) could induce pathological lesions in the livers, slightly change the serum biochemical parameters, and damage the hepatic antioxidant functions when the inclusion of AFB(1)- and AFB(2)-contaminated corn reached or exceeded 50%.

Novel protective mechanisms for S-adenosyl-l-methionine against acetaminophen hepatotoxicity: Improvement of key antioxidant enzymatic function

Acetaminophen (APAP) overdose leads to severe hepatotoxicity, increased oxidative stress and mitochondrial dysfunction. S-adenosyl-l-methionine (SAMe) protects against APAP toxicity at a mmol/kg equivalent dose to N-acetylcysteine (NAC). SAMe acts as a principle biological methyl donor and participates in polyamine synthesis which increase cell growth and has a role in mitochondrial protection. The purpose of the current study tested the hypothesis that SAMe protects against APAP toxicity by maintaining critical antioxidant enzymes and markers of oxidative stress. Male C57Bl/6 mice were treated with vehicle (Veh; water 15ml/kg, ip), SAMe (1.25mmol/kg, ip), APAP (250mg/kg, ip), and SAMe+APAP (SAMe given 1h following APAP). Liver was collected 2 and 4h following APAP administration; mitochondrial swelling as well as hepatic catalase, glutathione peroxidase (GPx), glutathione reductase, and both Mn- and Cu/Zn-superoxide dismutase (SOD) enzyme activity were evaluated. Mitochondrial protein carbonyl, 3-nitrotyrosine cytochrome c leakage were analyzed by Western blot. SAMe significantly increased SOD, GPx, and glutathione reductase activity at 4h following APAP overdose. SAMe greatly reduced markers of oxidative stress and cytochrome C leakage following APAP overdose. Our studies also demonstrate that a 1.25mmol/kg dose of SAMe does not inhibit CYP 2E1 enzyme activity. The current study identifies a plausible mechanism for the decreased oxidative stress observed when SAMe is given following APAP.

Nickel induces hyperglycemia and glycogenolysis and affects the antioxidant system in liver and white muscle of goldfish Carassius auratus L.

The toxicity of nickel to mammals is well studied, whereas information on nickel effects on fish is scant. Goldfish exposure to 10–50mgL−1 of waterborne Ni2+ for 96h showed reduced glycogen levels by 27–33% and 37–40% in liver and white muscle, respectively, accompanied by substantial increases in blood glucose levels (by 15–99%). However, indices of oxidative damage to proteins (carbonyl proteins) and lipids (lipid peroxides) were largely unaffected by nickel exposure. In liver, the activities of antioxidant enzymes, superoxide dismutase (SOD) and glutathione peroxidase (GPx), were not affected by Ni2+ treatment, while catalase activity was elevated by 26%. In white muscle, however, substantial increases in SOD (by 38–147%) and GPx (by 2.5–5.5-fold) activities appeared to compensate for decreased catalase activity (by 59–69%) in order to resist Ni-induced oxidative perturbations. Both hepatic and muscular glutathione reductase activities were suppressed by 10–30% and 12–21%, respectively, after goldfish exposure to all Ni2+ concentrations used. However, the activity of glucose-6-phosphate dehydrogenase was remarkably enhanced (by 1.6–5.4-fold) in white muscle of Ni-exposed fish, indicating a strong potential increase in NADPH production under Ni exposure. Thus, the exposure of goldfish to 10–50mgL−1 of Ni2+ for 96h induces glycogenolysis and hyperglycemia, showing some similarities with a hypoxia response, and leads to a substantial activation of defense systems against reactive oxygen species in liver and white muscle in tissue-specific and concentration-dependent manner.

Silymarin and naringenin protects nicotine induced oxidative stress in young rats

Protective efficacy of silymarin, a flavonoids complex known as ‘milk thistle’ and extracted from the fruit of Silybum marianum (L.) Gaertn. (Carduus marianus L., Asteraceae), and narigenin, a citrus bioflavanoid commonly found in citrus fruits, were studied against nicotine induced hepatic oxidative stress in young rats. Recent studies have shown that silymarin and naringenin possess antioxidant and free radical scavenging properties. Male wistar rats were injected with nicotine hydrogen tartarate (0.75mg/kg, intraperitoneally) and simultaneously given oral treatment with silymarin and naringenin (50 mg/kg each) for 21days to evaluate hepatic damage and antioxidant potential. Our results demonstrate a significant decrease in hepatic glutathione peroxidase (GPx) and glutathione reductase (GR) activities and an increase in glutathione S-transferase (GST) and thiobarbituric acid reactive substances (TBARs) levels on nicotine exposure. A similar trend was observed in blood and brain biochemical variables. Co-supplementation of silymarin or naringenin with nicotine was beneficial in the recovery of altered TBARS levels and GPx, GR and GST activity. Our results thus indicate the antioxidant potential of these flavonoids, which might be of benefit in the clinical recovery of subject exposed to nicotine. We thus recommend that diet rich in flavonoids may be of help in protecting nicotine-induced cytotoxicity.

Effect of exposure to perfluorooctanoic acid on hepatic antioxidants in mice

The present study was undertaken to evaluate hepatic antioxidants status in female mice after exposure to perfluorooctanoic acid (PFOA). A total number of 20 female mice were subjected to the study; out of them, 15 mice were treated with PFOA. PFOA solutions were prepared at 0.1, 0.5, and 1 mg/ml of deionized water and administered to the mice by gavage once daily for 3 weeks at a volume of 10 ml/kg. Controls (five mice) received an equivalent volume of deionized water. The results revealed significant increase in liver weight at dose of 5 (p < 0.01) and 10 mg/kg body weight (b.w., p < 0.01). Both hepatic total glutathione level and hepatic catalase activity were significantly increased (p < 0.01) at dose of 5 mg/kg b.w. On the other hand, hepatic glutathione reductase activity was significantly increased at dose of 10 mg/kg b.w. In this model system, PFOA administration was effective in inducing oxidative stress particularly reflected in the liver.

Effect of dietary selenium level on growth performance, body composition and hepatic glutathione peroxidase activities of largemouth bassMicropterus salmoide

An 8-week growth trial was conducted to determine the effect of dietary selenium (Se) level on growth performance, body composition and hepatic glutathione peroxidase (GPx) activities of largemouth bass. Sodium selenite was added to the fish meal basal diet at 0, 0.2, 0.4, 0.6, 0.8 and 1.0 mg kg−1 Se providing 0.97, 1.17, 1.42, 1.60, 1.85 and 2.06 mg Se kg−1 diet respectively. Each diet was fed to triplicate groups of fish (initial mean body weight: 4.95 ± 0.03 g) in a closed indoor recirculating system. The Se concentration in the rearing water was not detectable during the whole experimental period. The highest weight gain was obtained in fish fed diets with 1.60 mg Se kg−1, which was significant higher (P 0.05) with the other treatments. Feed conversion ratio, protein efficiency ratio, protein productive value, apparent digestibility coefficients of dry matter and muscle composition were not significantly impacted (P > 0.05) by dietary treatments. Fish fed diets with ≥1.42 mg Se kg−1 obtained higher liver lipid contents than treatments with lower dietary Se levels. Hepatic malondialdehyde (MDA) was unchanged (P > 0.05) in relation to dietary Se concentration. Hepatic GPx and glutathione reductase (GR) activities markedly increased and decreased (P < 0.05) with increasing dietary Se concentration, respectively, and both reached a plateau with ≥1.85 mg Se kg−1. Based on growth performance, hepatic MDA and enzymatic responses of GPx and GR, the highest Se concentration (2.06 mg kg−1) employed in our study was not harmful for largemouth bass, and the optimal dietary level should be 1.60–1.85 mg Se kg−1 from sodium selenite, at a dietary vitamin E level of 400 IU kg−1.

Influence of Selenium on Hepatic Mitochondrial Antioxidant Capacity in Ducklings Intoxicated with Aflatoxin B1

The aim of the study was to investigate the effect of selenium on hepatic mitochondrial antioxidant capacity in ducklings administrated with aflatoxin B(1) (AFB(1)). Ninety 7-day-old ducklings were randomly divided into three groups (groups I-III). Group I was used as a blank control. Group II was administered with AFB(1) (0.1 mg/kg body weight). Group III was administered with AFB(1) (0.1 mg/kg body weight) plus selenium (sodium selenite, 1 mg/kg body weight). All treatments were given once daily for 21 days. The results showed that the activities of mitochondrial superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione reductase (GR) in group II ducklings significantly decreased when compared with group I (P < 0.01). Furthermore, the content of hepatic mitochondrial malondialdehyde (MDA) significantly increased (P < 0.01). However, the activities of hepatic mitochondrial SOD, CAT, GSH-Px, and GR in group III ducklings significantly increased when compared with group II (P < 0.05). In addition, the content of hepatic mitochondrial MDA significantly decreased (P < 0.01). These results revealed that AFB(1) significantly induced hepatic mitochondrial antioxidant dysfunction. However, sodium selenite could significantly ameliorate the negative effect induced by AFB(1).

Antioxidant activity of guaiazulene and protection against paracetamol hepatotoxicity in rats.

The effect of guaiazulene, a lipophilic azulene derivative widely found in nature, on radical-mediated processes is examined. The ability of guaizulene to inhibit rat hepatic microsomal membrane lipid peroxidation and to scavenge hydroxyl radicals, as well as to interact with 1,1-diphenyl-2-picrylhydrazyl radical (DPPH), was estimated. It was found that guaiazulene can inhibit lipid peroxidation very significantly, having an IC50 value of 9.8 microM. It can also scavenge hydroxyl radicals and interact with DPPH. The protection afforded by guaiazulene to rats with paracetamol-induced liver injury was also investigated. Paracetamol hepatotoxicity is caused by the reactive metabolite N-acetyl-p-benzoquinone imine (NAPQI), which causes oxidative stress and glutathione (GSH) depletion. Hepatic cytosolic protein, GSH, glutathione transferase and glutathione reductase levels are determined as indices of hepatic injury with or without the administration of guaiazulene. It was found that all parameters affected by paracetamol are restored to normal by guaiazulene treatment, while the administration of guaiazulene alone has no effect on the performed tests compared with the control values. It was concluded that the significant protection against paracetamol-induced GSH depletion and hepatic damage afforded by guaiazulene is probably connected with its antioxidant activity. A molecular mechanism of action of guaiazulene is suggested.

Antilithogenic influence of dietary capsaicin and curcumin during experimental induction of cholesterol gallstone in mice

Spice bioactive compounds, capsaicin and curcumin, were both individually and in combination examined for antilithogenic potential during experimental induction of cholesterol gallstones in mice. Cholesterol gallstones were induced by feeding mice a high-cholesterol (0.5%) diet for 10weeks. Groups of mice were maintained on a lithogenic diet that was supplemented with 0.015% capsaicin/0.2% curcumin/0.015% capsaicin+ 0.2% curcumin. The lithogenic diet that contained capsaicin, curcumin, or their combination reduced the incidence of cholesterol gallstones by 50%, 66%, and 56%, respectively, compared with lithogenic control. This was accompanied by reduced biliary cholesterol and a marginal increase in phospholipid in these spice-fed groups. Increased cholesterol saturation index and cholesterol: phospholipid ratio in the bile caused by the lithogenic diet was countered by the dietary spice compounds. The antilithogenic influence of spice compounds was attributable to the cholesterol-lowering effect of these dietary spices in blood and liver, as well as a moderate increase in phospholipids. Decreased activities of hepatic glutathione reductase and glutathione-S-transferase caused by the lithogenic diet were countered by the combination of capsaicin and curcumin. The increased lipid peroxidation and the decreased concentration of ascorbic acid in the liver that was caused by the lithogenic diet was countered by the dietary spice compounds, individually or in combination. Thus, while the capsaicin and curcumin combination did not have an additive influence in reducing the incidence of cholesterol gallstones in mice, their combination nevertheless was more beneficial in enhancing the activity of hepatic antioxidant enzyme ─ glutathione reductase in the lithogenic situation. The antioxidant effects of dietary spice compounds are consistent with the observed reduction in cholesterol gallstones formed under lithogenic condition.