Hepatic Antioxidant Enzyme Activities Research Articles

Anti‐hypercholesterolemic influence of the spice cardamom (Elettaria cardamomum) in experimental rats

Cardamom (Elettaria cardamomum) is an aromatic seed spice grown extensively in India and used as a flavoring in sweets. In this study, the anti-hypercholesterolemic effect of cardamom was evaluated in Wistar rats by inducing hypercholesterolemia with a high-cholesterol diet for 8 weeks. Dietary interventions were made with (a) cardamom powder (50 g kg-1 ), (b) cardamom oil (3 g kg-1 , equivalent to 50 g kg-1 cardamom) and (c) de-oiled cardamom powder (50 g kg-1 ). A significant reduction in blood total cholesterol (31%) and low-density lipoprotein cholesterol (44%) was observed by oral administration of cardamom oil in hypercholesterolemic rats, accompanied by a marked decrease in serum triglycerides by 42%. The cholesterol content of cardiac muscle was beneficially lowered by 39% with administration of cardamom oil in hypercholesterolemic rats. Liver triglycerides were reduced by 33%. Incorporation of cardamom oil/powder in the diet did not alter feed consumption by rats. Compromised activities of hepatic antioxidant enzymes in the hypercholesterolemic situation were generally countered by dietary cardamom. Treatment with de-oiled cardamom as well as cardamom oil countered the diminished activity of catalase in hypercholesterolemic animals. Cardamom also enhanced the activity of heart superoxide dismutase in the hypercholesterolemic situation. The concentration of ascorbic acid in serum was significantly increased by dietary cardamom or its fractions in the hypercholesterolemic situation. This animal study has established the potential of cardamom oil in restoring the alteration in lipid homeostasis in conditions of hypercholesterolemia. The significant reduction in atherogenicity index by dietary intervention with cardamom powder and cardamom oil indicates the potential cardioprotective effect of cardamom. © 2016 Society of Chemical Industry.

Effects of zinc bearing palygorskite supplementation on the growth performance, hepatic mineral content, and antioxidant status of broilers at early age

ObjectiveThis study was conducted to investigate effects of zinc (Zn) bearing palygorskite (ZnPal) supplementation on growth performance, hepatic mineral content, and antioxidant status of broilers at early age.MethodsA total of 240 1-day-old Arbor Acres broiler chicks were allocated into 5 treatments with 6 replicates of 8 chicks each. Birds in 5 treatments were fed a basal diet supplemented with 0 (Control group; Analyzed Zn content: 81 mg/kg), 20, 40, 60, and 80 mg/kg Zn as ZnPal for 21 days, respectively. Blood, liver and intestinal mucosa were collected at 21 days of age.ResultsTreatments did not affect growth performance of broilers during the 21-day study (p> 0.05). The contents of hepatic Zn and magnesium (Mg) were linearly increased (p<0.001) by ZnPal supplementation. ZnPal inclusion linearly (p = 0.007) reduced malondialdehyde (MDA) concentration in serum. The activity of total superoxide dismutase (T-SOD) in liver increased linearly (p = 0.001) with concentration of ZnPal in diet. ZnPal inclusion linearly (p = 0.036) and quadratically (p = 0.005) increased T-SOD activity, and linearly (p = 0.012) increased copper/zinc superoxide dismutase (Cu/Zn SOD) activity in jejunal mucosa. The maximum responses of hepatic and jejunal antioxidant enzymes activities (T-SOD and Cu/Zn SOD) were found when supplementing the basal diet with 60 mg/kg Zn as ZnPal. Furthermore, ZnPal supplementation quadratically (p = 0.001) increased Cu/Zn SOD activity in ileal mucosa, and its maximum activity was observed in the diet supplemented with 20 mg/kg Zn as ZnPal.ConclusionZnPal supplementation did not alter growth performance of broilers. Dietary ZnPal inclusion could increase concentrations of hepatic trace minerals (Zn and Mg) and inhibit lipid peroxidation by reducing serum MDA accumulation, with the optimal dosage of Zn from ZnPal being 80 mg/kg diet (analyzed Zn content in the diet: 165 mg/kg), and 60 mg/kg Zn as ZnPal (analyzed Zn content in the diet: 148 mg/kg) was the optimum dosage for broilers to achieve maximum antioxidant enzyme activities.

Dietary supplementation of heat-treated Gracilaria and Ulva seaweeds enhanced acute hypoxia tolerance in gilthead sea bream (Sparus aurata).

ABSTRACTIntensive aquaculture practices involve rearing fish at high densities. In these conditions, fish may be exposed to suboptimal dissolved O2 levels with an increased formation of reactive O2 species (ROS) in tissues. Seaweeds (SW) contain biologically active substances with efficient antioxidant capacities. This study evaluated the effects of dietary supplementation of heat-treated SW (5% Gracilaria vermiculophylla or 5% Ulva lactuca) on stress bioindicators in sea bream subjected to a hypoxic challenge. 168 fish (104.5 g average weight) were distributed in 24 tanks, in which eight tanks were fed one of three experimental diets for 34 days: (i) a control diet without SW supplementation, (ii) a control diet supplemented with Ulva, or (iii) a control diet with Gracilaria. Thereafter, fish from 12 tanks (n=4 tanks/dietary treatment) were subjected to 24 h hypoxia (1.3 mg O2 l−1) and subsequent recovery normoxia (8.6 mg O2 l−1). Hypoxic fish showed an increase in hematocrit values regardless of dietary treatment. Dietary modulation of the O2-carrying capacity was conspicuous during recovery, as fish fed SW supplemented diets displayed significantly higher haemoglobin concentration than fish fed the control diet. After the challenge, survival rates in both groups of fish fed SW were higher, which was consistent with a decrease in hepatic lipid peroxidation in these groups. Furthermore, the hepatic antioxidant enzyme activities were modulated differently by changes in environmental O2 condition, particularly in sea bream fed the Gracilaria diet. After being subjected to hypoxia, the gene expression of antioxidant enzymes and molecular chaperones in liver and heart were down regulated in sea bream fed SW diets. This study suggests that the antioxidant properties of heat-treated SW may have a protective role against oxidative stress. The nature of these compounds and possible mechanisms implied are currently being investigated.

Genetically Engineered Escherichia coli Nissle 1917 Synbiotics Reduce Metabolic Effects Induced by Chronic Consumption of Dietary Fructose.

AimsTo assess protective efficacy of genetically modified Escherichia coli Nissle 1917 (EcN) on metabolic effects induced by chronic consumption of dietary fructose.Materials and MethodsEcN was genetically modified with fructose dehydrogenase (fdh) gene for conversion of fructose to 5-keto-D-fructose and mannitol-2-dehydrogenase (mtlK) gene for conversion to mannitol, a prebiotic. Charles foster rats weighing 150–200 g were fed with 20% fructose in drinking water for two months. Probiotic treatment of EcN (pqq), EcN (pqq-glf-mtlK), EcN (pqq-fdh) was given once per week 109 cells for two months. Furthermore, blood and liver parameters for oxidative stress, dyslipidemia and hyperglycemia were estimated. Fecal samples were collected to determine the production of short chain fatty acids and pyrroloquinoline quinone (PQQ) production.ResultsEcN (pqq-glf-mtlK), EcN (pqq-fdh) transformants were confirmed by restriction digestion and functionality was checked by PQQ estimation and HPLC analysis. There was significant increase in body weight, serum glucose, liver injury markers, lipid profile in serum and liver, and decrease in antioxidant enzyme activity in high-fructose-fed rats. However the rats treated with EcN (pqq-glf-mtlK) and EcN (pqq-fdh) showed significant reduction in lipid peroxidation along with increase in serum and hepatic antioxidant enzyme activities. Restoration of liver injury marker enzymes was also seen. Increase in short chain fatty acids (SCFA) demonstrated the prebiotic effects of mannitol and gluconic acid.ConclusionsOur study demonstrated the effectiveness of probiotic EcN producing PQQ and fructose metabolizing enzymes against the fructose induced hepatic steatosis suggesting that its potential for use in treating fructose induced metabolic syndrome.

Hypolipidemic and antioxidant effects of ethanol extract of Cassia fistula fruit in hyperlipidemic mice

Context: The plant Cassia fistula L. (Caesalpiniaceae) fruit was widely used by traditional practitioners to treat cardiovascular diseases (CVDs) in India. Hyperlipidemia is a lipid metabolism disorder and the major risk factor for the development of CVDs. Although most of the current hypolipidemic drugs are expensive and have potential side effects, the research focusing on natural alternative medicines is relevant.Objective: To investigate the hypolipidemic and antioxidant effects of ethanol extract of C. fistula fruit (CFE) in high-fat diet (HFD) induced hyperlipidemia in mice.Materials and methods: Oral administration of CFE at 100, 300 and 500 mg/kg body weight on HFD induced hyperlipidemia mice for 30 days. The standard drug atorvastatin (20 mg/kg) was used to compare the efficacy of CFE. Hypolipidemic effect was evidenced by the measurement of serum lipid profile and further confirmed by Oil Red O staining of adipose tissue. The hepatic and cardiac melondialdehyde (MDA) level and antioxidant enzyme activities including superoxide dismutase, catalase and glutathione peroxidase were determined.Results: Treatment with CFE at different doses has significantly restored the levels of serum lipid, MDA and enzymes activities in the liver and heart of hyperlipidemia mice. Oil Red O staining of visceral adipose tissue has shown marked reduction of lipid accumulation in adipocytes; whereas, administration of CFE at 500 mg/kg showed remarkable (p < 0.001) hypolipidemic and antioxidant effects in HFD fed mice.Conclusion: C. fistula fruit demonstrated hypolipidemic and antioxidant properties in vivo and the results corroborate the use of this plant in traditional medicine for cardiac ailments.

Protective effects of garlic oil against 1,3-dichloro-2-propanol-induced hepatotoxicity: role of CYP2E1 and MAPKs

1,3-Dichloro-2-propanol (1,3-DCP) is a well-known food contaminant that can be detected during the production of a wide range of foods. We investigated whether garlic oil (GO) has protective effects against 1,3-DCP-induced hepatotixicy and oxidative damage in rats. GO significantly attenuated the 1,3-DCP-induced increase in serum aminotransferase activities. This effect was accompanied by attenuation of the histopahological alterations in liver caused by 1,3-DCP. In 1,3-DCP-treated rats, GO prevented formation of hepatic malondialdehyde and depletion of reduced glutathione content, and promoted hepatic antioxidant enzymes activities. 1,3-DCP caused apoptosis in the liver with increases phosphorylation of mitogen-activated protein kinases (MAPKs); GO significantly attenuated these alterations and suppressed the expression of hepatic cytochrome P450 2E1 (CYP2E1). These results suggest that the protective effects of GO against 1,3-DCP-induced hepatotoxicity involve the ability to induce antioxidant enzymes, block metabolic activation of 1,3-DCP by suppressing CYP2E1 expression, and induce antiapoptotic activity by inhibiting phosphorylation of MAPKs.

Prevention of Aflatoxin B1 Hepatoxicity by Dietary Selenium Is Associated with Inhibition of Cytochrome P450 Isozymes and Up-Regulation of 6 Selenoprotein Genes in Chick Liver

Background: The involvement of cytochrome P450 (CYP450) isozymes and the selenogenome in selenium-mediated protection against aflatoxin B1 (AFB1)-induced adverse effects in broilers remains unclear.Objective: This study was designed first to determine whether selenium could reduce AFB1-induced hepatotoxic effects and then to determine whether these effects were due to changes in the CYP450 isozymes and selenogenome expression in the liver of chicks.Methods: Male avian broilers (aged 120 d) were allocated to 4 groups with 5 replicates of 6 birds to be included in a 2-by-2 factorial trial in which the main factors included supplementation of AFB1 (<5 compared with 100 μg/kg) and selenium (0.2 compared with 0.5 mg/kg) in a corn/soybean-based diet for 4 wk. Serum biochemistry, hepatic histology, and mRNA and/or activities of hepatic antioxidant enzymes, CYP450 isozymes, and 26 selenoproteins were analyzed at week 2 and/or 4.Results: Administration of AFB1 induced liver injury, decreasing (P < 0.05) total protein and albumin concentrations by 33.3–43.8% and increasing (P < 0.05) alanine aminotransferase and aspartate aminotransferase activities by 26.0–33.8% in serum, and induced hepatic necrosis and bile duct hyperplasia at week 2. AFB1 also decreased (P < 0.05) hepatic activities of glutathione peroxidase (GPX), thioredoxin reductase (TXNRD), and catalase, and the glutathione concentration by 13.1–59.9% and increased (P < 0.05) malondialdehyde, 8-hydroxydeoxyguanosine and exo-AFB1-8,9-epoxide (AFBO) DNA concentrations by 17.9–1200%. In addition, the mRNA and activity of enzymes responsible for the bioactivation of AFB1 into AFBO, which included CYP450 A1, 1A2, 2A6, and 3A4, were significantly induced (P < 0.05) by 29.2–271% in liver microsomes after 2-wk exposure to AFB1. These alterations induced by AFB1 were prevented by selenium supplementation. Dietary selenium supplementation increased (P < 0.05) mRNA and/or activities of 6 selenoprotein genes (Gpx3, Txnrd1, Txnrd2, Txnrd3, iodothyronine deiodinase 2, and selenoprotein N) in the liver of AFB1-treated groups at week 2.Conclusions: Dietary selenium protected chicks from AFB1-induced liver injury, potentially through the synergistic actions of inhibition of the pivotal CYP450 isozyme-mediated activation of AFB1 to toxic AFBO, and increased antioxidant capacities by upregulation of selenoprotein genes coding for antioxidant proteins.

Effect of 17α-methyltestosterone (MT) on oxidation stress in the liver of juvenile GIFT tilapia, Oreochromis niloticus.

The normal dose of 17α-methyltestosterone (MT) used in fish farming was 60 mg/L, and now the analysis of residual androgens was carried out in waste water obtained from the Beijing area, which could be detected in levels ranging from 4.1 to 7.0 ng/L. For the purpose of aquatic early warning, the present study clearly demonstrated that chronic exposure by higher concentration of MT than environmental relevant concentrations could trigger oxidative stress response to juvenile tilapia by modulating hepatic antioxidant enzyme activities and gene transcription. Some antioxidative parameters (T-GSH, GSH/GSSG and MDA) were significant decreased under 0.5 mg/L MT exposure at 7 and 14 days. Some antioxidant enzymes (SOD, CAT and GST) and transcriptional changes (sod and cat) were revealed significant decreases for MT treated groups at 7 days. Total antioxidant capacity was significant increased only in 5 mg/L MT exposure groups, but GR activities were not affected all through the whole exposure period. Almost all of the antioxidant enzymatic genes detected in the present study were showed significant increments for MT exposure both at 14 and 21 days, and the genotoxicity profile of antioxidant enzymatic genes were revealed dose-dependent manner. This study presented evidence that MT could result in oxidative stress response in the early stages of GIFT tilapia.Electronic supplementary materialThe online version of this article (doi:10.1186/s40064-016-1946-6) contains supplementary material, which is available to authorized users.

Hepatoprotective effect of resveratrol against ethanol-induced oxidative stress through induction of superoxide dismutase in vivo and in vitro.

The present study aimed to investigate the hepatoprotective effect of resveratrol (RSV) against ethanol-induced oxidative stress in vivo, and investigate the underlying mechanisms by which RSV exerts its anti-oxidative effects on hepatic cells. C57BL/6J mice were divided into four groups: Untreated control, ethanol-treated, RSV-treated, and ethanol + RSV-treated. The plasma lipid profile, hepatic lipid accumulation and antioxidative enzyme activities were analyzed. HepG2 cells were used as a cellular model to analyze the effects of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and peroxisome proliferator-activated receptors (PPARs) in the RSV-mediated protection of ethanol-induced oxidative stress. In C57BL/6J mice, ethanol caused a significant increase in plasma triglyceride levels and hepatic lipid accumulation (P<0.05), whereas RSV notably increased SOD activity. In HepG2 cells, SOD activity was enhanced in the RSV-treated HepG2 cells, whereas the activity of CAT and GPx was not affected. Western blot and quantitative polymerase chain reaction analyses demonstrated that RSV significantly increased SOD protein and mRNA expression levels (P<0.05). Using a transient transfection assay, PPARγ was observed to participate in the regulation of SOD gene expression in RSV-administered HepG2 cells. To conclude, the results from the present study suggest that RSV may contribute towards the protection of hepatic cells from ethanol-induced oxidative stress via the induction of SOD activity and gene expression.

Vescalagin from Pink Wax Apple [Syzygium samarangense (Blume) Merrill and Perry] Alleviates Hepatic Insulin Resistance and Ameliorates Glycemic Metabolism Abnormality in Rats Fed a High-Fructose Diet.

This study investigates the ameliorative effect of vescalagin (VES) isolated from Pink wax apple fruit on hepatic insulin resistance and abnormal carbohydrate metabolism in high-fructose diet (HFD)-induced hyperglycemic rats. The results show that in HFD rats, VES significantly reduced the values of the area under the curve for glucose in an oral glucose tolerance test and the homeostasis model assessment of insulin resistance index. VES significantly enhanced the activity of hepatic antioxidant enzymes while reducing thiobarbituric acid-reactive substances in HFD rats. Western blot assay revealed that VES reduced hepatic protein expression involved in inflammation pathways while up-regulating expression of hepatic insulin signaling-related proteins. Moreover, VES up-regulated the expression of hepatic glycogen synthase and hepatic glycolysis-related proteins while down-regulating hepatic gluconeogenesis-related proteins in HFD rats. This study suggests some therapeutic potential of VES in preventing the progression of diabetes mellitus.

Aerobic interval exercise improves parameters of nonalcoholic fatty liver disease (NAFLD) and other alterations of metabolic syndrome in obese Zucker rats

Metabolic syndrome (MS) is a group of metabolic alterations that increase the susceptibility to cardiovascular disease and type 2 diabetes. Nonalcoholic fatty liver disease has been described as the liver manifestation of MS. We aimed to test the beneficial effects of an aerobic interval training (AIT) protocol on different biochemical, microscopic, and functional liver alterations related to the MS in the experimental model of obese Zucker rat. Two groups of lean and obese animals (6 weeks old) followed a protocol of AIT (4 min at 65%-80% of maximal oxygen uptake, followed by 3 min at 50%-65% of maximal oxygen uptake for 45-60 min, 5 days/week, 8 weeks of experimental period), whereas 2 control groups remained sedentary. Obese rats had higher food intake and body weight (P < 0.0001) and suffered significant alterations in plasma lipid profile, area under the curve after oral glucose overload (P < 0.0001), liver histology and functionality, and antioxidant status. The AIT protocol reduced the severity of alterations related to glucose and lipid metabolism and increased the liver protein expression of PPARγ, as well as the gene expression of glutathione peroxidase 4 (P < 0.001). The training protocol also showed significant effects on the activity of hepatic antioxidant enzymes, although this action was greatly influenced by rat phenotype. The present data suggest that AIT protocol is a feasible strategy to improve some of the plasma and liver alterations featured by the MS.

Antidiabetic, antioxidant, antihyperlipidemic effect of extract of Euryale ferox salisb. with enhanced histopathology of pancreas, liver and kidney in streptozotocin induced diabetic rats.

BackgroundEthanolic extract of Euryale ferox salisb. (EFx) may have an effect on the activity of hepatic antioxidant enzymes, glycemic control and lipid profile and histopathology of pancreas, liver and kidney of streptozotocin (STZ)—induced diabetic wistar rats.MethodsWistar albino rats were divided into eight groups viz. non-diabetic (normal control), diabetic control (STZ-induced), diabetic treated (infused with different doses of Euryale ferox. Salisb. ethanolic extract) and diabetic conventional treated (treated with Glibenclamide). Diabetes was induced by administering streptozotocin (60 mg/kg body weight) intraperitoneal (i.p). The ethanolic extract was supplemented in different doses through oral route. Biochemical investigations were carried out according to previously reported methods. Histopathological examinations were done accordingly.ResultsThe EFx supplemented diabetic rats significantly (p < 0.001) decreased the blood glucose level in a dose dependent manner. Plasma insulin level was significantly increased in EFx treated rats. The hepatic gluconeogenic enzymes activities were restored to normal in EFx treated rats. Activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and reduced glutathione (GSH) were significantly increased (p < 0.001) among EFx treated rats. Lipid profile was reinstated to nearly normal level among EFx treated rats. Histopathological investigations revealed that microscopic architecture of pancreatic, hepatic and renal cells improvised in EFx treated diabetic rats.ConclusionEFx supplement could improve the glycemic control as well as lipid profile in diabetic rats along with improvised antioxidant enzymes which has beneficial effect in preventing the diabetic complications by scavenging the free radicals in diabetic rats.

Hepatic biotransformation and antioxidant enzyme activities in Mediterranean fish from different habitat depths

Marine fish are threatened by anthropogenic chemical discharges. However, knowledge on adverse effects on deep-sea fish or their detoxification capabilities is limited. Herein, we compared the basal activities of selected hepatic detoxification enzymes in several species (Solea solea, Dicentrarchus labrax, Trachyrhynchus scabrus, Mora moro, Cataetix laticeps and Alepocehalus rostratus) collected from the coast, middle and lower slopes of the Blanes Canyon region (Catalan continental margin, NW Mediterranean Sea). The xenobiotic-detoxifying enzymes analysed were the phase-I carboxylesterases (CbEs), and the phase-II conjugation activities uridine diphosphate glucuronyltransferase (UDPGT) and glutathione S-transferase (GST). Moreover, some antioxidant enzyme activities, i.e., catalase (CAT), glutathione peroxidase (GPX) and glutathione reductase (GR), were also included in this comparative study. Because CbE activity is represented by multiple isoforms, the substrates α-naphthyl acetate (αNA) and ρ-nitrophenyl acetate (ρNPA) were used in the enzyme assays, and in vitro inhibition kinetics with dichlorvos were performed to compare interspecific CbE sensitivity.Activity of xenobiotic detoxification enzymes varied among the species, following a trend with habitat depth and body size. Thus, UDPGT and some antioxidant enzyme activities decreased in fish inhabiting lower slopes of deep-sea, whereas UDPGT and αNA-CbE activities were negatively related to fish size. A trend between CbE activities and the IC50 values for dichlorvos suggested S. solea and M. moro as potentially more sensitive to anticholinesterasic pesticides, and T. scabrus as the most resistant one. A principal component analysis considering all enzyme activities clearly identified the species but this grouping was not related to habitat depth or phylogeny. Although these results can be taken as baseline levels of the main xenobiotic detoxification enzymes in Mediterranean fish, further research is needed to evaluate their response to environmental contaminant exposure.

Effect of Tofu Manufactured from Lipoxygenase-free Genotypes Soybean on the Fecal Lipid Level and Hepatic Antioxidant Enzyme Activity in Rat Fed a High Fat-cholesterol Diet

Effect of Tofu Manufactured from Lipoxygenase-free Genotypes Soybean on the Fecal Lipid Level and Hepatic Antioxidant Enzyme Activity in Rat Fed a High Fat-cholesterol Diet

Chronic effects of tributyltin on multiple biomarkers responses in juvenile common carp, Cyprinus carpio.

In this study, the chronic toxic effects of tributyltin (TBT), an antifouling paints commonly present in surface and ground water, on morphological indices, reactive oxygen species (ROS) generation, and ATPase activity and heat shock protein (Hsp) 70 protein in tissues (liver, gill, and white muscle) of common carp were investigated. Fish were exposed at sublethal concentrations of TBT (75 ng/L, 0.75 μg/L, and 7.5 μg/L) for 60 days. When compared with the control, there was significant lower condition factor in fish exposed at the higher concentration of TBT. ROS levels in three tissues increased significantly at higher TBT concentrations (0.75 and 7.5 μg/L). The hepatic antioxidant enzymes (total antioxidative capacity and superoxide dismutase) activities were induced at higher concentrations (0.75 μg/L) of TBT. When compared with the hepatic antioxidant enzymes activities in fish exposed to 0.75 μg/L of TBT, there was a decreasing trend in those exposed to TBT with a concentration of 7.5 μg/L. However, all the antioxidant enzymes activities were significantly inhibited in gill and muscle of fish exposed to higher TBT concentrations (0.75 and 7.5 μg/L). Moreover, there was significant lower Na-K-ATPase in three tissues after long-term exposure to higher concentration of TBT, but a significant higher Hsp70 protein levels was observed. In short, environmental concentrations of TBT could not induce obvious impacts on fish, but long-term exposure to higher concentrations of TBT could affect seriously the health status of fish. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 937-944, 2016.

Effect of curcumin on hepatic antioxidant enzymes activities and gene expressions in rats intoxicated with aflatoxin B1.

Twenty-eight rats were examined in a 5-week experiment to investigate the effect of curcumin on gene expression and activities of hepatic antioxidant enzymes in rats intoxicated with aflatoxin B1 (AFB1 ). The rats were divided into four groups. Rats in 1-4 groups served as control, oral curcumin treated (15 mg/kg body weight), single i.p. dose of AFB1 (3 mg/kg body weight) and combination of single i.p. dose of AFB1 with oral curcumin treated, respectively. AFB1 Liver damage and oxidative stress were evident in untreated AFB1 -intoxicated rats as indicated by a significant elevation in hepatic transaminases, elevation in lipid peroxide biomarkers (thiobarbituric acid reactive substances; TBARS), reduction of reduced glutathione (GSH) concentration, reduction in the activities of antioxidant enzymes namely catalase (CAT), total superoxide dismutase (SOD), glutathione peroxidase (GPX) and glutathione-S-transferase (GST) and down-regulation of gene expression of these antioxidant enzymes compared to control. Liver sections of rats intoxicated with AFB1 showed a disrupted lobular architecture, scattered necrotic cells and biliary proliferation. Administration of curcumin with AFB1 resulted in amelioration of AFB1 -induced effects compared to untreated AFB1 -intoxicated rats via an up-regulation of antioxidant enzyme gene expression, activation of the expressed genes and increase in the availability of GSH.

Comparative Hepatoprotective Activity of Ethanolic Extracts of Cuscuta australis against Acetaminophen Intoxication in Wistar Rats.

This study investigates the comparative hepatoprotective activity of crude ethanol extracts of Cuscuta australis against acetaminophen (APAP) intoxication. Thirty-six rats were randomly divided into six groups of 6 replicates: Group 1 which served as control received water. Group 2 was orally administered 835 mg/kg body wt. of paracetamol on day 8. Groups 3 and 4 were orally administered ethanolic extracts of the seed of Cuscuta australis in doses of 125 mg/kg and 250 mg/kg, respectively, for 7 days and then intoxicated as in Group 2 on the 8th day. Groups 5 and 6 received similar oral doses of Cuscuta australis stem extracts for 7 days and then intoxicated as in Groups 3 and 4. Group 2 rats showed severe periportal hepatic necrosis, significantly elevated serum hepatic injury markers, markedly increased lipid peroxidation, and decreased hepatic antioxidant enzymes activities. Remarkably, Cuscuta australis (seed and stem) extract pretreatments in Groups 3, 4, 5, and 6, most especially, the stem extract pretreatment in Groups 5 and 6, improved better the hepatic histoarchitecture, the hepatocellular, and the oxidative stress injury markers in a dose-dependent manner. Conclusively, ethanol extractions of Cuscuta australis stem appear to protect the liver from acetaminophen intoxication better than the seed counterpart.

Preventive effects of ZPDC glycoprotein (24 kDa) on hepatotoxicity induced by mercury chloride in vitro and in vivo.

Mercury is a potent environmental contaminant that exerts toxic effect on various vital organs in the human body. Recently, we isolated glycoprotein from Zanthoxylum piperitum DC (ZPDC), which has antioxidant and anticancer effects. In the present study, we determined the preventive effects of ZPDC glycoprotein on hepatic damage induced by mercury chloride (HgCl2 ). We evaluated the activities of lactate dehydrogenase (LDH), alanine aminotransferase (ALT), antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)], extracellular signal-regulated kinase (ERK)1/2, p38 mitogen-activated protein kinase (MAPK), cyclo-oxygenase (COX-2), inducible nitric oxide synthetase (iNOS), and activator protein (AP-1) and the quantitative expressions of nuclear factor E2-related factor (Nrf2), heme oxygenase (HO-1), metallothionein (MT) and reduced glutathione (GSH) in mercury-chloride-exposed (50 μM and 10 mg/kg body weight) primary cultured hepatocytes and ICR mice, using biochemical assays, radioactivity and immunoblot analysis. The results demonstrated that ZPDC glycoprotein decreased the levels of LDH, ALT, HO-1 and MT, whereas it increased the activities of hepatic antioxidant enzymes (SOD, CAT and GPx) and reduced GSH in mercury-chloride-exposed primary cultured hepatocytes. Also, it suppressed arachidonic acid release and expression of ERK, p38 MAPK, COX-2, iNOS, AP-1 and Nrf-2 in primary cultured hepatocytes and ICR mice exposed to mercury chloride. Collectively, ZPDC glycoprotein may have potential applications to prevent hepatotoxicity induced by mercury chloride.

The protective effect of Phoenix dactylifera L. seeds against CCl4-induced hepatotoxicity in rats

Ethnopharmacological relevanceIn traditional Egyptian medicine, Phoenix dactylifera L. (date palm) seeds are listed in folk remedies for the management of diabetes, liver diseases and gastrointestinal disorders. The present study was conducted to investigate the protective effect of Phoenix dactylifera L. seeds aqueous suspension against the chemically-induced hepatic injury in rats. MethodsLiver injury was achieved by exposing Wistar rats to CCl4 (10% in olive oil; 0.5mL/rat; IP) twice a week for 4 weeks. Along with CCl4, aqueous suspensions of raw or roasted Phoenix dactylifera seeds (1.0g/kg) were administered orally in a daily manner. ResultsOur results demonstrated that Phoenix dactylifera seeds significantly improved the CCl4-induced alterations in liver function parameters (AST, ALT, ALP and albumin). Moreover, the CCl4-induced oxidative stress, represented by elevated thiobarbituric acid reactive substance (TBARS), nitric oxide and oxidative DNA damage, was ameliorated by Phoenix dactylifera seeds treatment. In addition, Phoenix dactylifera seeds restored the activities of hepatic antioxidant enzymes (superoxide dismutase and glutathione S-transferase) that were declined after CCl4 treatment. Examination of liver histopathology revealed that Phoenix dactylifera seeds attenuate the incidence of liver lesions (including vacuolization and fibroblast proliferation) triggered by CCl4 intoxication. ConclusionThe Phoenix dactylifera seeds could be a promising candidate for protection against the CCl4-induced liver intoxication, and this hepatoprotective effect might be attributed to the antioxidant and free radical scavenging activities.

Temporal changes in hepatic antioxidant enzyme activities after ischemia and reperfusion in a rat liver ischemia model: effect of dietary fish oil.

This study investigated the hypothesis that administration of tilapia fish oil diet would attenuate warm liver ischemia/reperfusion injury (IRI) and whether fish oil modulates prooxidant/antioxidant status. Male Wistar rats were subjected to 30 min of approximately 70% hepatic ischemia followed by 1, 12, and 24 h reperfusion. Rats were randomly divided into three groups: sham-operated group (SO), control-warm hepatic ischemia (WI) group, and Oil-WI group given tilapia oil for 3 weeks followed by liver IRI. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were measured in the plasma. Levels of thiobarbituric acid reactive substances (TBARS) and antioxidant enzymes as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities were measured in liver fractions. In the sham group, there was no enzymatic or histological change. I/R caused significant increase in serum AST, ALT, and tissue TBARS levels. As compared to the control group, animals treated with tilapia oil experienced a significant decrease (p < 0.05) in AST and ALT levels in reperfusion periods. Tissue TBARS levels in Oil-WI group were significantly (p < 0.05) reduced as compared to control group at 60 min after reperfusion. After ischemia, 1, 12, and 24 h of reperfusion, CAT, SOD, and GPx values were the lowest in the Oil-WI group and highest in the control group and were statistically significant (p < 0.05). Histological analysis also revealed that fish oil provided some protection compared with the control group. Tilapia oil exerts a protective effect during the early phase of reperfusion, and it modulates prooxidant/antioxidant status of rat liver subjected to warm IRI.