Biochemical changes induced in liver and serum of aflatoxin B1-treated male wistar rats: preventive effect of picroliv

Administration of aflatoxin B1 to rats (2 mg/kg intraperitoneally) caused significant increase in the activities of gamma-glutamyl transpeptidase, 5'-nucleotidase, acid phosphatase, acid ribonuclease as well as content of lipid peroxides in liver after six weeks. However, the activities of succinate dehydrogenase, glucose-6-phosphatase, catalase, superoxide dismutase, glutathione-S-transferase, glutathione peroxidase and glutathione reductase in liver were decreased. The levels of glycogen and reduced glutathione were also decreased. There were significant elevations in the levels of serum transaminases, phosphatases (acid and alkaline), dehydrogenases (sorbitol, lactate and glutamate) and bilirubin following aflatoxin B1 administration. Picroliv (25 mg/kg/day orally for six weeks), an iridoid glycoside isolated from the roots and rhizomes of Picrorhiza kurroa, significantly prevented the biochemical changes induced by aflatoxin B1.     

Comparative effects of curcumin and resveratrol on aflatoxin B1-induced liver injury in rats

Aflatoxin B₁ is a potent hepatotoxic and hepatocarcinogenic mycotoxin. Lipid peroxidation and oxidative DNA damage are the principal manifestations of aflatoxin B₁-induced toxicity that could be counteracted by antioxidants. Many plant constituents have been reported to prevent liver damage associated with lipid peroxidation. In this study, curcumin (polyphenolic antioxidant purified from turmeric) and resveratrol (polyphenol obtained from grapes) were evaluated for possible protection against liver injury induced by aflatoxin B₁ in rats. Adult male Fischer rats were divided into six groups including untreated control, curcumin control (200 mg/kg BW), resveratrol control (10 mg/kg BW) and aflatoxin B₁ (25 μg/kg BW). Other two groups were administered either curcumin or resveratrol along with aflatoxin B₁. The study was carried out for 90 days. At the end of the experiment period, blood and tissue samples were collected from the animals before they were killed. Livers were collected for histopathologic studies and fixed in 10% buffered formalin solution. Serum was used for estimation of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyl transferase (γ-GT) enzymes. The lipid peroxidation, reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were estimated in liver homogenates. The results revealed that aflatoxin B₁ administration caused liver damage as indicated by statistically significant (P < 0.05) increase in serum ALT, AST and γ-GT levels. In addition, there were general statistically significant reductions in the activities of GSH, SOD, CAT, GSH-Px, and an increase in lipid peroxidation in the liver of aflatoxin B₁-treated group compared to the untreated control group. Curcumin showed a significant hepatoprotective activity by lowering the levels of serum marker enzymes, lipid peroxidation and elevating the levels of GSH, SOD, CAT and GSH-Px. However, resveratrol failed to protect from the aflatoxin B₁-induced liver injury. These findings suggest that curcumin but not resveratrol has a hepatoprotective effect against aflatoxin B₁-induced liver injury.     

Hepatocurative effect of picroliv and silymarin against aflatoxin B1 induced hepatotoxicity in rats

Single doses of aflatoxin B1 (2 mg/kg, i.p.) caused significant increases in the activities of tau-glutamyl transpeptidase, 5'-nucleotidase, acid phosphatase and acid ribonuclease, and decreases in the activities of succinate dehydrogenase and glucose-6-phosphatase in liver, after 8 weeks. The level of lipid peroxides, DNA, RNA, and cholesterol increased while glycogen decreased. It also increased the serum level of transaminases, sorbitol dehydrogenase, glutamate dehydrogenase, lactate dehydrogenase, acid phosphatase, alkaline phosphatase, and bilirubin. Oral administration of picroliv (25 mg/kg/day for 15 days), a standardised iridoid glycoside fraction of Picrorhiza kurroa, 6 weeks after aflatoxin B1 toxication, significantly prevented the biochemical changes induced in liver and serum of aflatoxin B1 treated rats. The hepatocurative effect of picroliv and silymarin, a plant based standard hepatoprotective are comparable.     

Changes in hepatic polyamine levels during acute and chronic administration of aflatoxin B1 to rats

A subacute dose of aflatoxin B₁ (3 mg/kg body weight) increases liver putrescine levels within 1 hr after administration, with high levels persisting over 24 hr. Higher doses of the carcinogen elicited larger increases in liver polyamine levels. A marked elevation of putrescine, spermidine and spermine were noted in aflatoxin B₁-induced preneoplastic liver. Pretreatment of rats with phenobarbital prior to aflatoxin B₁ administration resulted in no synergistic or additive effects.     

Effect of ammoniation on the toxicity of corn artificially contaminated with aflatoxin B1

The effect of an aqueous ammonia treatment of aflatoxin B₁-containing corn was determined on toxicity of the corn administered orally to male Fischer rats. Corn was contaminated with aflatoxin B₁ (5 mg/g corn) and administered per se (2.0 or 4.0 g corn/kg) or after treatment with ammonium hydroxide. Body weight changes, liver weight, hexobarbital sleeping times, hepatic microsomal concentrations of protein and cytochromes P-450 and b₅, and mortality were determined 72 hr after dosing with corn, and serum alkaline phosphatase activity was determined 96 hr after dosing. The ammonia treatment of contaminated corn prevented the changes in these parameters caused by aflatoxin B₁. Ammoniation of corn free of aflatoxin had no adverse effect on the parameters, although ammoniation per se did raise the concentrations of hepatic microsomal protein. The results of the study indicate that ammoniation may prevent acute aflatoxicosis produced by aflatoxin-contaminated corn.     

Effects of aflatoxin B1 on the activity of drug-metabolizing enzymes in rat liver

Aflatoxin B₁ (AFB₁) is one of the most active hepatotoxic and hepatocarcinogenic compounds known for rats. In order to evaluate the mechanism of action of the toxin on the liver, the effects of aflatoxin B₁ on the enzymes involved in its transformation, such as the monooxygenase-cytochromes P-450-dependent and conjugating enzymes, were studied. At the same time, liver damage was determined by measuring the activities of plasma γ-glutamyltransferase (GGT), alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) as well as the concentration of bilirubin.Male Sprague-Dawley rats received a single ip dose of AFB₁ (1 or 3 mg/kg). The effects of the toxic compound on the activity of drug-metabolizing enzymes were followed 20 days after this single exposure. Mortality (18%) within 7 days following administration was produced only by the higher dose. The same dose also significantly decreased the total level of hepatic proteins and impaired the activity of aminopyrine N-demethylase. AFB₁ lowered the content of cytochromes P-450 by 32 and 69% at the 1 and 3 mg/kg dose levels, respectively. Epoxide hydrase activity was increased by 121 and 170% at 1 and 3 mg/kg, respectively, whereas UDP-glucuronyltransferase activity was increased (44%) at 1 mg/kg, but also decreased at the same extent for the higher dose. The activity of GSH S-epoxide transferase was decreased by a maximum of 53% by 3 mg/kg AFB₁. Results obtained by the 3rd day following the administration of 3 mg/kg AFB₁ showed that blood levels of all the factors studied in this experiment were increased above control values, while at lower dose of AFB₁ (1 mg/kg), only the activities of AST and ALT were significantly increased. The activities of these enzymes were 27 to 42 times greater in rats treated with 3 mg/kg AFB₁ than in rats given 1 mg/kg AFB₁. Most of the biological features studied tended to return to control values between the 9th and 20th day after AFB₁ treatment. This study makes it possible to compare changes in tissue levels of drug-metabolizing enzymes at two doses of AFB₁. It can also be used to demonstrate any time lag or differing behavior of the serum enzymes, notably the sensibility of transaminases.     

Experimental induction of liver fibrosis in young guinea pigs by combined application of copper sulphate and aflatoxin B1

Aflatoxin B₁ alone (0.05 mg resp. 0.037 mg/kg/d), copper alone (6.6 mg/kg/d or 200 mg/l drinking water) or a combination of both was administered orally for 6 months to young guinea pigs from the first/second day of life. In the copper group there were no pathomorphological changes. For the aflatoxin B₁ group, liver damage was established. In the combined group, liver injury was more frequent and more severe compared to the aflatoxin B₁ group and biliary copper excretion was diminished compared with the copper group. Histologically, only the livers of this group exhibited degeneration, atrophy and steatosis of liver cells, inflammatory processes and a more or less prominent fibrosis. For childhood cirrhosis (ICC and ICT) a combined etiology—a liver damaging agent plus elevated alimentary copper—is a plausible hypothesis.     

Protective Effect of Ebselen on Aflatoxin B1‐Induced Cytotoxicity in Primary Rat Hepatocytes

Recent studies have shown that aflatoxin B₁ enhances reactive oxygen species formation and causes oxidative damage, which may ultimately contribute to the cytotoxicity and carcinogenic effect of aflatoxin B₁. Ebselen, 2‐phenyl‐1,2‐benzoisoseleazol‐3(H)‐one, a synthetic seleno‐organic compound has been shown to possess glutathione peroxidase‐like activity and free radical scavenging ability. Thus present study was designed to investigate the protective effect of ebselen on aflatoxin B₁‐induced cytotoxicity in primary rat hepatocytes. Aflatoxin B₁‐induced cytotoxicity and lipid peroxidation were determined by lactate dehydrogenase leakage and malondialdehyde generation, respectively. Intracellular reactive oxygen species level was measured using the fluorescent probe 2′,7′‐dichlorofluorescin diacetate, and the intracellular reduced glutathione concentration was determined with a fluorometric method. Ebselen was found to display a dose‐dependent protective effect on lactate dehydrogenase leakage and malondialdehyde generation caused by aflatoxin B₁ exposure. The results also demonstrate that ebselen efficiently inhibits the intracellular reactive oxygen species formation in aflatoxin B₁‐treated hepatocytes in a dose and time‐dependent manner. It was also noted that ebselen was able to increase the intracellular reduced glutathione concentration, both in the control and in aflatoxin B₁‐treated hepatocytes. The protection of ebselen against aflatoxin B₁ cytotoxicity, however, was not affected by lowering the concentration of intracellular reduced glutathione. The overall data indicate that ebselen possesses a potent protective effect against aflatoxin B₁‐induced cytotoxicity, and the main mechanism involved in the protection may be its strong capability in inhibiting intracellular reactive oxygen species formation and preventing oxidative damage.     

Aflatoxin B1 epoxidation catalysed by partially purified human liver lipoxygenase

(1) This study demonstrates for the first time the human liver lipoxygenase-mediated co-oxidation of aflatoxin B₁ to the reactive metabolite, aflatoxin B₁-8,9-epoxide, which rapidly hydrolyzes to dihydrodiol and preferentially binds to Tris. (2) The Tris- diol complex formed was quantitated fluorimetrically, based on its characteristic excitation at λ_ex 395 nm and emission at λ_em 435 nm. (3) The incubation of partially purified human liver lipoxygenase for 30?min under optimum assay conditions (3.5 mM linoleic acid and 50 μM aflatoxin B₁ in Tris buffer atpH 7.2) resulted in the formation of 10 ± 1.7 nmol Tris- diol/mg protein. (4) In addition to linoleic acid, other unsaturated fatty acids namely γ-linolenic acid, cis-11,14-eicosadienoic acid and arachidonic acid also supported the lipoxygenase mediated epoxidation of aflatoxin B₁. (5) The enzymatic Tris- diol formation was significantly inhibited by all the lipoxygenase inhibitors tested in a concentration-dependent manner. (6) These results strongly suggest that lipoxygenase is capable of aflatoxin B₁ metabolism and this may represent yet another pathway for the bioactivation of this hepatocarcinogen in the human liver.     

Protective Effects of Bacillus subtilis ANSB060 on Serum Biochemistry,Histopathological Changes and Antioxidant Enzyme Activities of Broilers Fed Moldy Peanut Meal Naturally Contaminated with Aflatoxins

The aim of this study was to investigate the toxic effects of aflatoxins and evaluate the effectiveness of Bacillus subtilis ANSB060 in detoxifying aflatoxicosis in broilers. A total of 360 one-week-old male broilers (Ross 308) were assigned to six dietary treatments for five weeks. The treatment diets were: C0 (basal diet); C1.0 (C0 + 1.0 g B. subtilis ANSB060/kg diet); M0 (basal diet formulated with moldy peanut meal); M0.5, M1.0 and M2.0 (M0 + 0.5, 1.0 and 2.0 g B. subtilis ANSB060/kg diet, respectively). The contents of aflatoxin B₁, B₂, G₁ and G₂ in the diets formulated with moldy peanut meal were 70.7 ± 1.3, 11.0 ± 1.5, 6.5 ± 0.8 and 2.0 ± 0.3 µg/kg, respectively. The results showed that aflatoxins increased (p < 0.05) serum aspartate transaminase activity, decreased (p < 0.05) serum glutathione peroxidase activity, and enhanced (p < 0.05) malondialdehyde contents in both the serum and liver. Aflatoxins also caused gross and histological changes in liver tissues, such as bile duct epithelium hyperplasia, vacuolar degeneration and lymphocyte infiltration. The supplementation of ANSB060 reduced aflatoxin levels in the duodenum and counteracted the negative effects of aflatoxins, leading to the conclusion that ANSB060 has a protective effect against aflatoxicosis and this protection is dose-related.     

The antioxidant effects of pumpkin seed oil on subacute aflatoxin poisoning in mice

This study was aimed at the investigation of the antioxidant effect of pumpkin seed oil against the oxidative stress‐inducing potential of aflatoxin. For this purpose, 48 male BALB/c mice were used. Four groups, each comprising 12 mice, were established. Group 1 was maintained as the control group. Group 2 was administered with pumpkin seed oil alone at a dose of 1.5 mL/kg.bw/day (～1375mg/kg.bw/day). Group 3 received aflatoxin (82.45% AFB₁, 10.65% AFB₂, 4.13% AFG_1, and 2.77% AFG₂) alone at a dose of 625 μg/kg.bw/day. Finally, group 4 was given both 1.5 mL/kg.bw/day pumpkin seed oil and 625 μg/kg.bw/day aflatoxin. All administrations were oral, performed with the aid of a gastric tube and continued for a period of 21 days. At the end of day 21, the liver, lungs, kidneys, brain, heart, and spleen of the animals were excised, and the extirpated tissues were homogenized appropriately. Malondialdehyde (MDA) levels and catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH‐Px) activities were determined in tissue homogenates. In conclusion, it was determined that aflatoxin exhibited adverse effects on most of the oxidative stress markers. The administration of pumpkin seed oil diminished aflatoxin‐induced adverse effects. In other words, the values of the group, which was administered with both aflatoxin and pumpkin seed oil, were observed to have drawn closer to the values of the control group. © 2011 Wiley Periodicals, Inc. Environ Toxicol 28: 681–688, 2013.     

Lipoic acid attenuates Aroclor 1260‐induced hepatotoxicity in adult rats

The present study was aimed to investigate the mechanistic aspect of Aroclor 1260‐induced hepatotoxicity and its protection by lipoic acid. The adult male Albino rats were divided into six groups. Group I served as control. Group II received lipoic acid (35 mg/kg/day). Aroclor 1260 was given to rats by oral gavage at doses 20, 40, or 60 mg/kg/day (Groups III, IV, and V, respectively). Group VI was pretreated with lipoic acid (35 mg/kg/day) 24 h before Aroclor 1260 (40 mg/kg/day). Treatment in all groups was continued for further 15 consecutive days. Serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase activities and total bilirubin, total cholesterol, and triglycerides were significantly increased while total protein, total albumin, and high‐density lipoprotein were significantly decreased. Hydrogen peroxide production and lipid peroxidation were significantly increased while superoxide dismutase and catalase activities and reduced glutathione (GSH) content was significantly decreased in liver. Caspase‐3 & ‐9 activities were significantly increased in liver. Lipoic acid pretreatment significantly reverted all these abnormalities toward their normal levels. In conclusion, Aroclor 1260 induced liver dysfunction, at least in part, by induction of oxidative stress. Apoptotic effect of hepatic cells is involved in Aroclor 1260‐induced liver injury. Lipoic acid could protect rats against Aroclor 1260‐induced hepatotoxicity. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 913–922, 2016.     

Protective effects of melatonin in reduction of oxidative damage and immunosuppression induced by aflatoxin B1‐contaminated diets in young chicks

In the present study, the ability of aflatoxin B₁ (AFB₁) to induce endogenous oxidative damages and the possible ameliorating effects of dietary melatonin (MEL) were investigated. Newly hatched broiler chicks (n = 240) were fed aflatoxin‐contaminated diets (0.5 or 1 mg kg^?1 diet) with or without MEL (40 mg kg^?1 bw) supplementation in diet for 40 days. AFB₁ resulted in a significant increase in lipid peroxidation (LPO) in the liver and erythrocytes accompanied with suppression of superoxide dismutase (SOD) and catalase (CAT) enzyme activities of erythrocytes. It also caused a significant reduction in levels of serum proteins and marked elevation in activities of serum transaminases. AFB₁ treatment also decreased both humoral and cell‐mediated immune responses in growing chicks. Simultaneous administration of MEL with AFB₁ resulted in an obvious improvement in all the tested parameters. Long‐term rather than short‐term administration of MEL was more effective in rendering protection against AFB₁‐induced toxicity. © 2009 Wiley Periodicals, Inc. Environ Toxicol 26: 153–160, 2011.     

Influence of aflatoxin B 1 and aflatoxin B 2 on rat liver lysosomal acid deoxyribonuclease

The in vitro effects of aflatoxins B₁ and B₂ were studied on the permeability of isolated rat liver lysosomes. Only aflatoxin B₁ altered the lysosomal membrane with the consequent release of lysosomal enzymes. The results of the in vivo experiment with aflatoxin B₁ show that the specific activity of acid DNase in liver lysosomes was markedly decreased in the rats dosed aflatoxin B₁ while the specific activity of the cytoplasmic acid DNase, or nonsedimentable acid DNase, was dramatically increased. The results are discussed in relation to a hypothesis concerning the role of lysosomes in carcinogenesis.     

Hepatoprotective and antioxidant effects of gallic acid in paracetamol‐induced liver damage in mice

Objectives The aim of this research paper was to investigate the hepatoprotective and antioxidant effects of gallic acid in paracetamol‐induced liver damage in mice. Methods In the present study, the hepatoprotective and antioxidant effects of gallic acid were evaluated against paracetamol‐induced hepatotoxicity in mice and compared with the silymarin, a standard hepatoprotective drug. The mice received a single dose of paracetamol (900 mg/kg body weight i.p.). Gallic acid (100 mg/kg body weight i.p.) and silymarin (25 mg/kg body weight i.p.) were administered 30 min after the injection of paracetamol. After 4 h, liver marker enzymes (aspartate transaminase, alanine transaminase and alkaline phosphatase) and inflammatory mediator tumour necrosis factor‐alpha (TNF‐α) were estimated in serum, while the lipid peroxidation and antioxidant status (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione‐S‐transferase and glutathione) were determined in liver homogenate of the control and experimental mice. Key findings Increased activities of liver marker enzymes and elevated TNF‐α and lipid peroxidation levels were observed in mice exposed to paracetamol (P < 0.05), whereas the antioxidant status was found to be depleted (P < 0.05) when compared with the control group. However gallic acid treatment (100 mg/kg body weight i.p.) significantly reverses (P < 0.05) the above changes by its antioxidant action compared to the control group as observed in the paracetamol‐challenged mice. Conclusions The results clearly demonstrate that gallic acid possesses promising hepatoprotective effects.     

Effect of a Lignan-Enriched Extract of Schisandra Chinensis on Aflatoxin B1 and Cadmium Chloride-Induced Hepatotoxicity in Rats

Abstract: Treatment of rats with a lignan-enriched extract of the fruit of Schisandra chinensis could enhance hepatic antioxidant/detoxification system, as indicated by increases in hepatic reduced glutathione (GSH) level as well as hepatic glutathione reductase and glutathione S-transferase activities. The hepatoprotective action was evident after aflatoxin β₁ or cadmium chloride (Cd) challenge. Schisandra chinensis pretreatment protected against aflatoxin B₁ or Cd-induced hepatocellular damage in rats. However, pretreating rats with α-tocopherol acetate (vitamin E) did not protect against hepatic damage induced by both toxins. Results from the present as well as our previous studies demonstrate that the hepatoprotection afforded by Schisandra chiensis pretreatment is not hepatotoxin specific. Schisandra chinensis seems to be more effective than vitamin E in protecting against aflatoxin B₁ and Cd toxicity. The mechanism of hepatoprotection afforded by Schisandra chinensis pretreatment may involve facilitation of both antioxidant and detoxification processes in the liver.     

Effects of tebuconazole on cytochrome P450 enzymes,oxidative stress,and endocrine disruption in male rats

The major objective of the present study was to determine the ability of a triazole fungicide tebuconazole to induce cytochrome P450‐dependent monooxygenases, oxidative stress, and endocrine‐disrupting activity using male rats treated with tebuconazole at 10, 25, and 50 mg/kg p.o. once daily for 28 days. In liver, tebuconazole dose‐dependently increased microsomal contents of cytochrome P450 and cytochrome b₅ and the activities of NADPH‐cytochrome P450 reductase, 7‐ethoxyresorufin O‐deethylase, methoxyresorufin O‐demethylase, pentoxyresorufin O‐dealkylase, 7‐ethoxycoumarin O‐deethylase, aniline hydroxylase, and erythromycin N‐demethylase. In kidney, tebuconazole increased 7‐ethoxycoumarin O‐deethylase activity without affecting other monooxygenase activities. In marked contrast to liver and kidney, tebuconazole decreased testicular 7‐ethoxyresorufin O‐deethylase, methoxyresorufin O‐demethylase, 7‐ethoxycoumarin O‐deethylase, aniline hydroxylase, and erythromycin N‐demethylase activities. The results of immunoblot analysis of liver microsomes of controls and tebuconazole‐treated rats revealed that tebuconazole induced CYP1A1/2, CYP2B1/2, CYP2E1, and CYP3A proteins in liver. Additions of tebuconazole to liver microsomes inhibited microsomal 7‐ethoxycoumarin O‐deethylase activity in vitro (IC₅₀ = 1.50–1.69 µM). Treatment of rats with tebuconazole decreased glutathione content and increased glutathione S‐transferase, superoxide dismutase, catalase, and glutathione peroxidase activities in liver; increased superoxide dismutase activities in kidney and testis; but decreased glutathione S‐transferase activity in testis. Treatments with tebuconazole decreased serum testosterone concentration and cauda epididymal sperm count. The present study demonstrates that tebuconazole induces a multiplicity of CYPs and oxidative stress in liver; inhibits testicular P450 and glutathione S‐transferase activities; and produces anti‐androgenic effects in male rats.     

Effect of aflatoxin B1 on brain serotonin and catecholamines in chickens

A single oral dose of aflatoxin B₁ at 3 mg/kg body weight caused a significant increase in brain serotonin (5-HT) in 5-week-old chickens. Norepinephrine (NE) brain concentration significantly decreased, whereas the dopamine (DA) concentration remained unchanged. These results suggest that in modifying the concentrations of biogenic amines in the brain, aflatoxin B₁ may affect brain function.     

Andrographolide impairs alpha-naphthylisothiocyanate-induced cholestatic liver injury in vivo

To investigate if andrographolide impairs cholestatic liver injury. All rats were randomly divided into six groups—(1) control (n?=?6), (2) control?+?200 mg/kg andrographolide (n?=?6), (3) alpha-naphthylisothiocyanate (ANIT)-control (n?=?6), (4) ANIT?+?50 mg/kg andrographolide (n?=?6), (5) ANIT?+?100 mg/kg andrographolide (n?=?6), and (6) ANIT?+?200 mg/kg andrographolide (n?=?6). We gavaged 50 mg/kg ANIT to mimic cholestatic liver injury in rats. Seven days after treatment, all the rats were killed. Serum biochemistry and hepatic histopathological assays were performed to evaluate liver injury. We observed that 200 mg/kg andrographolide significantly decreased the level of alanine transaminase, aspartate aminotransferase, alkaline phosphatase, γ-glutamyltranspeptidase, total bilirubin, and total bile acid in the blood. It also markedly decreased hepatic interleukin-6 and tumor necrosis factor α. Furthermore, 200 mg/kg andrographolide significantly decreased malondialdehyde but increased superoxide dismutase, glutathione, and erythrocyte glutathione peroxidase. Moreover, 200 mg/kg andrographolide effectively increased the accumulation of sirtuin 1 and nuclear erythroid 2-related factor-2. It also attenuated the level of nuclear factor kappa-light-chain-enhancer of activated B and cyclooxygenase-2. These data suggest that andrographolide may impair cholestatic liver injury via anti-inflammatory and anti-oxidative stress.

     

Protective role of zinc during aluminum‐induced hepatotoxicity

The study was carried out to assess the role of zinc (Zn) in mitigating the biochemical alterations induced by aluminum (Al) in rat liver. Rats were divided into four groups: normal control, Al treated (AlCl₃, 100 mg/kg b.wt./day), Zn treated (ZnSO₄, 227 mg/L drinking water), and combined Al + Zn treated. Al and zinc treatments were given for a total duration of 2 months. Al treatment caused a significant increase in the activity of alkaline phosphatase (ALP), but decreased aspartate aminotransferase (AST) and alanine aminotranferase (ALT) activities, which showed the reverse trend following Zn supplementation. Levels of lipid peroxidation (LPx) and activities of catalase and glutathione‐S‐transferase (GST) were significantly decreased following Al treatment, which, however, were increased significantly in Zn co‐treated rats. Further Al exposure showed a significant increase in reduced glutathione (GSH) content as well as activities, of superoxide dismutase (SOD) and glutathione reductase (GR). However, Zn supplementation to Al‐treated rats brought down the raised levels of reduced (GSH) and SOD to within normal limits, but caused no effect on GR activity. Furthermore, Al treatment also resulted in alterations in liver histoarchitecture with disruption of hepatic cords and increased vacuolization, which were close to normal following Zn supplementation. The present study reveals that Zn is effective in attenuating the liver damage inflicted by Al toxicity. © 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 320–327, 2014.