Protective effects of sodium nitrite preconditioning against alcohol-induced acute liver injury in mice

The purpose of the present study was to investigate the effect of sodium nitrite (SN) on alcohol-induced acute liver injury in mice. Forty male C57bL/6 mice were randomly divided into 4 groups. Acute alcohol-induced liver injury group were injected intraperitoneal (ip) with alcohol (4.5 g/kg); SN preconditioning group were pretreated with SN (16 mg/kg, ip) for 12 h, and received alcohol (4.5 g/kg, ip) injection; Control and SN groups were treated with saline and SN, respectively. After the treatments, liver index (liver/body weight ratio) was determined. Colorimetric technique was performed to measure the serum alanine transaminase (ALT), aspartate transaminase (AST), liver superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) activities, as well as malondialdehyde (MDA) content. The pathological index of liver tissue was assayed by HE and TUNEL fluorometric staining. Using Western blot and immunohistochemistry staining, the expression of hypoxia-inducible factor-1α (HIF-1α) protein was detected. The results showed that, compared with acute alcohol-induced liver injury group, pretreatment with low doses of SN decreased liver index and serum levels of ALT and AST, weakened acute alcohol-induced hepatocyte necrosis, improved pathological changes in liver tissue, increased live tissue SOD, GSH-Px and CAT activities, reduced MDA content and apoptosis index of hepatocytes, and up-regulated HIF-1α protein level in liver tissue. These results suggest that the pretreatment of SN can protect hepatocytes against alcohol-induced acute injury, and the protective mechanism involves inhibition of oxidative stress and up-regulation of HIF-1α protein level.     

Effect of Cassia fistula Linn. leaf extract on diethylnitrosamine induced hepatic injury in rats

The hepatoprotective and antioxidant effect of Cassia fistula Linn. leaf extract on liver injury induced by diethylnitrosamine (DEN) was investigated. Wistar rats weighing 200+/-10g were administered a single dose of DEN (200mg/kg b.w., i.p.) and left for 30 days. For hepatoprotective studies, ethanolic leaf extract (ELE) of C. fistula Linn. (500mg/kg b.w., p.o.) was administered daily for 30 days. AST, ALT, ALP, LDH, gamma-GT and bilirubin were estimated in serum and liver tissue. Lipid peroxidation (LPO), SOD and CAT were also estimated in liver tissue as markers of oxidative stress. DEN induced hepatotoxicity in all the treated animals were evident by elevated serum ALT, AST, ALP and bilirubin levels and a simultaneous fall in their levels in the liver tissue after 30 days. Induction of oxidative stress in the liver was evidenced by increased LPO and fall in the activities of SOD and CAT. ELE administration for 30 days prevented the DEN induced hepatic injury and oxidative stress. In conclusion, it was observed that ELE of C. fistula Linn. protects the liver against DEN induced hepatic injury in rats.     

Activity of Cassia auriculata leaf extract in rats with alcoholic liver injury

This study was undertaken to investigate the effect of Cassia auriculata leaf extract on tissue lipid peroxidation and antioxidant status in experimental hepatotoxicity. Administering ethanol to rats for 60 days resulted in significantly elevated levels of serum total bilirubin, aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) as compared with those of the experimental control rats. Significantly elevated levels of tissue thiobarbituric acid reactive substances (TBARS), hydroperoxides and lowered activities of superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) were also observed on alcohol treatment as compared with those of experimental control rats. Concentration of serum non-enzymic antioxidants such as vitamin E and vitamin C were also significantly lowered on alcohol supplementation. Treatment with Cassia auriculata leaf extract at a dose of 250 mg kg(-1) body weight and 500 mg kg(-1) body weight to rats administered alcohol, lowered the levels of TBARS and hydroperoxides and elevated the activities of SOD and CAT and the levels of reduced GSH in the liver, brain, kidney and intestine significantly compared to unsupplemented alcohol treated rats. Cassia auriculata leaf extract treatment restored the serum vitamin E, and vitamin C levels also to near those of the experimental control animals. Our data indicate that supplementation with Cassia auriculata leaf extract can offer protection against free radical mediated oxidative stress in experimental hepatotoxicity. In addition, histopathological studies of the liver and brain confirmed the beneficial role of Cassia auriculata leaf extract.     

Protective role of Vitamin E pre-treatment on N-nitrosodiethylamine induced oxidative stress in rat liver

Nitrosamine compounds are known hepatic carcinogens. In the metabolism of nitrosamines, such as N-nitrosodiethylamine (NDEA), there is evidence of the formation of reactive oxygen species (ROS) resulting in oxidative stress, which may be one of the factors in the etiology of cancer. The formation of ROS may alter the antioxidant system, while the presence of Vitamin E may counteract NDEA induced oxidative stress. This study was planned to determine whether pre-treatment with Vitamin E (40 mg/kg body weight, i.p., twice a week for 4 weeks) to NDEA induced rats provides protection against oxidative stress in liver caused by the carcinogen. A single necrogenic dose of NDEA (200mg/kg body weight) was administered i.p. to the male albino rats with or without Vitamin E pre-treatment and the animals were sacrificed on Days 7, 14 or 21 after the administration of NDEA. The result showed enhanced levels of hepatic lipid peroxidation (LPO) and conjugated dienes of NDEA treated rats as the indices of oxidative stress, however, Vitamin E pre-treated rats administered NDEA showed decreased LPO and conjugated dienes (Day 21). Superoxide dismutase (SOD) activity in liver was not altered significantly in NDEA treated rats with or without Vitamin E pre-treatment. Catalase (CAT) activity was inhibited with NDEA treatment, however, Vitamin E pre-treatment showed recovery in hepatic CAT activity (Days 14 and 21). Total and Se-glutathione peroxidase (GSH-Px) activities and glutathione-S-transferase (GST) activity in liver increased in NDEA treated rats irrespective of Vitamin E pre-treatment. Glutathione reductase (GSH-R) activity as well as total glutathione (GSH) content in liver decreased in NDEA treated animals, both of which were recovered in Vitamin E pre-treated rats administered NDEA. Activities of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) were increased significantly following NDEA treatment to rats with or without Vitamin E pre-treatment. The activities of AST and ALT enzymes were significantly reduced on Days 14 and 21 and ALP activity was reduced on Day 21 in NDEA+Vitamin E treated animals when compared to NDEA treated alone. LDH enzyme activity was normalized on Day 14 in Vitamin E pre-treated animals administered NDEA. However, the AST, ALT and ALP enzyme activities remained high in all treatment groups as compared to control group. Normal control and Vitamin E treated alone rats revealed normal histology of liver. On the other hand, NDEA treated animals showed alterations in normal hepatic histoarchitecture, which comprised of necrosis and vacuolization of the cells. However, the rats treated with Vitamin E+NDEA showed that the liver cells were normal, with very little necrosis (Day 21). This study concludes that the pre-treatment with Vitamin E prior to the administration of NDEA, reduced the degree of oxidative stress, although this vitamin produced only slight changes in the hepatic injury, in a time-dependent manner.     

Anti-trichomonal, biochemical and toxicological activities of methanolic extract and some carbazole alkaloids isolated from the leaves of Murraya koenigii growing in Nigeria

The methanolic extract of Murraya koenigii leaf was screened for toxicological and biochemical effects on rats because of the folkloric uses as an anti-dysentery and anti-diabetes. The extract was moderately toxic (LD(50)=316.23 mg/kg body weight) to rats and had appreciable effect on the liver and kidney at higher doses leading to liver inflammation. It had little or no effect on haematology and relative organ weight of lungs, heart and spleen. Acute doses (500 mg/kg) reduced significantly serum globulin, albumin, urea, glucose, total protein, aspartate transaminase (AST), and increased cholesterol and alanine transaminase (ALT) indicating hepatic injury. However, chronic administration for 14 days gave a significant (p<0.05) reduction in the serum cholesterol, glucose, urea, bilirubin, ALT and AST showing that the plant has hypoglycaemic and hepatoprotective effects after prolonged use. The activity demonstrated by some of the isolated carbazole alkaloids and their derivatives against Trichomonas gallinae confirmed that the anti-trichomonal activity of the leaf may be due to its carbazole alkaloids. The order of activity was C(18)>C(23)>C(13). Girinimbine and girinimbilol with IC(50) values of 1.08 and 1.20 microg/ml were the most active. Acetylation of girinimbilol and mahanimbilol improved their activities to 0.60 and 1.08 microg/ml.     

Amelioration of carbon tetrachloride-induced hepatotoxicity and haemotoxicity by aqueous leaf extract of Cnidoscolus aconitifolius in rats

This study was conducted to explore possible protective effect ofCnidoscolus aconitifolius (CA) leaf extract on carbon tetrachloride (CCl4)-induced hepatotoxicity and haemotoxicity in experimental animal models. Thirty six rats of six per group were used in this study. Group I received 10ml/kg normal saline as control. Group II-VI rats were administered with 1.25ml/kg body weight (bwt) of carbon tetrachloride intraperitonealy. Animals in groups III, IV, V and VI were however pre-treated with aqueous extract of Cnidoscolus aconitifolius at 100, 250, 500 and 750mg/kg body weight (bwt) respectively. Administration of CCL4 in untreated rats led to microcytic hypochromic anaemia, thrombocytopenia, increased erythrocyte fragility and stress induced leucocytosis accompanied with significant increase in neutrophils and decrease in lymphocyte counts. CCl4 also led to significant increase in serum transaminases (ALT and AST) and phosphatase (ALP) respectively compared with control animals. Also, CCL4 produced significant increase in serum blood urea nitrogen (BUN) and creatinine compared with normal rats. Pre-treatment with Cnidoscolus aconitifolius leaf extract brought about significant restoration of the haematological parameters to values that were comparable to those of the control with concomitant decrease in the activities of the marker of hepatic damage enzymes (ALT, AST and ALP), in a dose-dependent manner. Similarly, serum levels of blood urea nitrogen (BUN) and creatinine were also brought to near normal by the CA in a dose-dependent manner. From this study, we conclude that pre-exposure to Cnidoscolus aconitifolius leaf extract considerably reduced the effect of CCl4 on the blood parameters and ameliorated hepatic damage by the haloalkane. Keywords: Hepatotoxicity, Haemotoxicity, Carbon tetrachloride, Cnidoscolus aconitifolius, Rats.     

Beneficial effect of nitric oxide synthase inhibitor on hepatotoxicity induced by allyl alcohol

The effect of aminoguanidine (a selective inhibitor of inducible nitric oxide synthase) on allyl alcohol-induced liver injury was assessed by the measurement of serum ALT and AST activities and histopathological examination. When aminoguanidine (50-300 mg/kg, i.p.) was administered to mice 30 min before a toxic dose of allyl alcohol (75 microL/kg, i.p.), significant changes related to liver injury were observed. In the presence of aminoguanidine the level of ALT and AST enzymes were significantly decreased. All symptoms of liver necrosis produced by allyl alcohol toxicity almost completely disappeared when animals were pretreated with aminoguanidine at 300 mg/kg. Depletion of hepatic glutathione as a consequence of allyl alcohol metabolism was minimal in mice pretreated with aminoguanidine at 300 mg/kg. It was found that the inhibition of toxicity was not due to alteration in allyl alcohol metabolism since aminoguanidine did not effect alcohol dehydrogenase activity both in vivo and in vitro.     

Potential preventive effect of carvacrol against diethylnitrosamine-induced hepatocellular carcinoma in rats

Antioxidants are one of the key players in tumorigenesis, several natural and synthetic antioxidants were shown to have anticancer effects. The aim of the present study is to divulge the chemopreventive nature of carvacrol during diethylnitrosamine (DEN)-induced liver cancer in male wistar albino rats. Administration of DEN to rats resulted in increased relative liver weight and serum marker enzymes aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and gamma glutamyl transpeptidase (γGT). The levels of lipid peroxides elevated (in both serum and tissue) with subsequent decrease in the final body weight and tissue antioxidants like superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), glutathione peroxidase (GPx), and glutathione reductase (GR). Carvacrol supplementation (15 mg/kg body weight) significantly attenuated these alterations, thereby showing potent anticancer effect in liver cancer. Histological observations and transmission electron microscopy studies were also carried out, which added supports to the chemopreventive action of the carvacrol against DEN-induction during liver cancer progression. These findings suggest that carvacrol prevents lipid peroxidation, hepatic cell damage, and protects the antioxidant system in DEN-induced hepatocellular carcinogenesis.     

Protective effects of ascorbic acid, dl-alpha-tocopherol acetate, and sodium selenate on ethanol-induced liver damage of rats

In this study, the effect of a combination of vitamin C (ascorbic acid), vitamin E (dl-alpha-tocopherol acetate), and selenium (sodium selenate) on ethanol-induced liver damage in rats was investigated, morphologically and biochemically. The ethanol-induced injury was produced by the administration of 1 mL of absolute ethanol to each rat. Animals received vitamin C (250 mg/kg), vitamin E (250 mg/kg), and selenium (0.5 mg/kg) (ViCESe) for 3 d 1 h prior to the administration of absolute ethanol. In the liver of the animals given ethanol, the degenerative changes such as extreme hyperemia, vacuolization in cells of portal areas, a dilation in sinusoids, mononuclear cell infiltration, a swelling in cisternae of granular endoplasmic reticulum and in mitochondrial cristae, an increase in smooth endoplasmic reticulum, many lipid vacuoles were observed both light and electron microscopically. A similar structure was usually distinguished when compared with control animals, in rats given ethanol + ViCESe. In this group, the findings indicating cellular damage were either not observed at all or were decreased. In the group administered ethanol, a reduction of the blood glutathione (GSH) level and increases in serum values of alanine aminotranserase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT) activities were observed, whereas in the control group, the reverse was found to occur. On the other hand, in the group in which ethanol + ViCESe was administered, it was observed that the blood GSH value and serum ALP and ALT activities increased and serum AST, LDH, and GGT activities decreased. As a result, the present study indicates that ViCESe because of their antioxidant activity against ethanol damage have a protective effect on the liver.     

Experimental analysis of gossypol and chloroquine interaction in serum and in liver of rat.

Interactive effects of gossypol and chloroquine as determined by activities of serum alanine transaminase (ALT), aspartate transaminase (AST) and liver lactate dehydrogenase (LDH), alkaline phosphatase (ALK-pase), glucose-6-phosphatase (G-6-pase) and cholesterol level were investigated in rats. Administration of gossypol for eight weeks, at a concentration of 20 mg per kg body wt. per day with or without chloroquine had no effect on the serum enzymes and glucose-6-phosphatase activities. When chloroquine at a concentration of 5 mg per kg body wt. thrice a week was administered alone, there was a marked decrease in total protein content and ALK-pose activities, while a significant increase in LDH activity was observed. Administration of either gossypol or chloroquine decreased the level of cholesterol. A greater decrease was recorded when both were given together. It is suggested that gossypol can be employed as a male contraceptive among malaria-infected populations.     

Vinpocetine ameliorates acute hepatic damage caused by administration of carbon tetrachloride in rats

Vinpocetine is a widely used drug for the treatment of cerebrovascular and memory disorders. This study aimed to investigate the effect of vinpocetine on the acute hepatic injury caused in the rat by the administration of CCl4 in vivo. Vinpocetine (2.1, 4.2, 8.4 mg/kg) or silymarin (30 mg/kg) was given once daily orally simultaneously with CCl4 and for 15 days thereafter. Liver damage was assessed by determining serum enzyme activities and hepatic histopathology. Stained sections were subjected to morphometric evaluation using computerized image analyzer. The results showed that vinpocetine administered to CCl4-treated rats decreased the elevated alanine aminotransferase (ALT) by 49.3, 58.1 and 63.6%, aspartate aminotransferase (AST) by 10.5, 22.6 and 27.2% and alkaline phosphatase (ALP) by 52.5, 59.6 and 64.9%, respectively, and in a dose-dependent manner. Meanwhile, silymarin reduced elevated ALT, AST and ALP levels by 53.1, 26.9 and 66%, respectively. Histological examination of liver specimens revealed a marked reduction in liver cell necrosis in vinpocetine and silymarin-treated rats compared with vehicle-treated CCl4-treated rats. Quantitative analysis of the area of damage showed 85.3% reduction in the area of damage after silymarin and 72.2, 78.9 and 82.6% reduction after vinpocetine treatment at 2.1, 4.2, 8.4 mg/kg, respectively. It is concluded that administration of vinpocetine in a model of CCl4-induced liver injury in rats reduced liver damage. The reduction obtained by 4.2 mg/kg of vinpocetine was similar to that obtained by 30 mg/kg silymarin. Therefore, it is suggested that vinpocetine might be a good pharmacological agent in the treatment of liver disease besides its neuroprotective effects.     

Effect of a polyherbal formulation, Ambrex, on butylated hydroxy toluene (BHT) induced toxicity in rats

Effect of polyherbal formulation Ambrex was evaluated in butylated hydroxytoluene (BHT) induced toxicity of lungs and liver in rats. Toxicity was produced by administering BHT (500 mg/kg/day) for 3 days. Lung damage was evidenced by elevated levels of broncho alveolar lavage fluid (BAL) parameters such as protein, lactate, lactate dehydrogenase (LDH), alkaline phosphatase (ALP), acid phosphatase (ACP) and glucose-6-phosphate dehydrogenase (G6PDH). Liver damage was proved by elevated levels of serum protein and markers such as LDH, ALP, aspartate amino transferase (AST), alanine amino transferase (ALT), decreased level of lipid peroxides (LPO) in serum and glutathione (GSH) in liver. Administration of aqueous suspension of Ambrex (50 mg/kg orally) retained these elevated levels of BAL-protein, lactate, LDH, ALP, ACP, G6PDH and serum-protein, LDH, ALP, AST and ALT at near normal values. Decreased level of liver GSH was retained at near normalcy in Ambrex pretreated BHT-administered animals. There was no change in liver LPO in all the four groups.     

Efficacy of caffeic acid in preventing nickel induced oxidative damage in liver of rats

Nickel (Ni), a major environmental pollutant, is known for its wide toxic manifestations. In the present study caffeic acid (CA), one of the most commonly occurring phenolic acids in fruits, grains and dietary supplements, was evaluated for its protective effect against the Ni induced oxidative damage in liver. In this investigation, Ni (20 mg/kg body weight) was administered intraperitoneally for 20 days to induce toxicity. CA was administered orally (15, 30 and 60 mg/kg body weight) for 20 days with intraperitoneal administration of Ni. Ni induced liver damage was clearly shown by the increased activities of serum hepatic enzymes namely aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT) and lactate dehydrogenase (LDH) along with increased elevation of lipid peroxidation indices (thiobarbituric reactive acid substances (TBARS) and lipid hydroperoxides). The toxic effect of Ni was also indicated by significantly decreased levels of enzymatic (superoxide dismutase (SOD), catalase (CAT) glutathione peroxidase (GPx) and glutathione S-transferase (GST)) and non-enzymatic antioxidants (glutathione (GSH), vitamin C and vitamin E). CA administered at a dose of 60 mg/kg body weight significantly reversed the activities of hepatic marker enzymes to their near normal levels when compared with other two doses. In addition, CA significantly reduced lipid peroxidation and restored the levels of antioxidant defense in the liver. All these changes were supported by histological observations. The results indicate that CA may be beneficial in ameliorating the Ni induced oxidative damage in the liver of rats.     

Potential chemoprevention of N-nitrosodiethylamine-induced hepatocarcinogenesis by polyphenolics from Acacia nilotica bark

Chemopreventive potential of Acacia nilotica bark extract (ANBE) against single intraperitoneal injection of N-nitrosodiethylamine (NDEA, 200 mg/kg) followed by weekly subcutaneous injections of carbon tetrachloride (CCl₄, 3 ml/kg) for 6 weeks induced hepatocellular carcinoma (HCC) in rats was studied. At 45 day after administration of NDEA, 100 and 200 mg/kg of ANBE were administered orally once daily for 10 weeks. The levels of liver injury and liver cancer markers such as alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), γ-glutamyl transferase (γ-GT), total bilirubin level (TBL), α-feto protein (AFP) and carcinoembryonic antigen (CEA) were substantially increased following NDEA treatment. However, ANBE treatment reduced liver injury and restored liver cancer markers. ANBE also significantly prevented hepatic malondialdehyde (MDA) formation and reduced glutathione (GSH) in NDEA-treated rats which was dose dependent. Additionally, ANBE also increased the activities of antioxidant enzymes viz., catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione-S-transferase (GST) in the liver of NDEA-administered rats. Eventually, ANBE also significantly improved body weight and prevented increase of relative liver weight due to NDEA treatment. Histological observations of liver tissues too correlated with the biochemical observations. HPLC analysis of ANBE showed the presence of gallic, protocatechuic, caffeic and ellagic acids, and also quercetin in ANBE. The results strongly support that A. nilotica bark prevents lipid peroxidation (LPO) and promote the enzymatic and non-enzymatic antioxidant defense system during NDEA-induced hepatocarcinogenesis which might be due to activities like scavenging of oxy radicals by the phytomolecules in ANBE.     

Protective effects of ascorbic acid, dl-α-tocopherol acetate, and sodium selenate on ethanol-induced liver damage of rats

In this study, the effect of a combination of vitamin C (ascorbic acid), vitamin E (dl-α-tocopherol acetate), and selenium (sodium selenate) on ethanol-induced liver damage in rats was investigated, morphologically and biochemically. The ethanol-induced injury was produced by the administration of 1 mL of absolute ethanol to each rat. Animals received vitamin C (250 mg/kg), vitamin E (250 mg/kg), and selenium (0.5 mg/kg) (ViCESe) for 3 d 1 h prior to the administration of absolute ethanol. In the liver of the animals given ethanol, the degenerative changes such as extreme hyperemia, vacuolization in cells of portal areas, a dilation in sinusoids, mononuclear cell infiltration, a swelling in cisternae of granular endoplasmic reticulum and in mitochondrial cristae, an increase in smooth endoplasmic reticulum, many lipid vacuoles were observed both light and electron microscopically. A similar structure was usually distinguished when compared with control animals, in rats given ethanol+ViCESe. In this group, the findings indicating cellular damage were either not observed at all or were decreased. In the group administered ethanol, a reduction of the blood glutathione (GSH) level and increases in serum values of alanine aminotranserase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and γ-glutamyl transferase (GGT) activities were observed, whereas in the control group, the reverse was found to occur. On the other hand, in the group in which ethanol+ViCESe was administered, it was observed that the blood GSH value and serum ALP and ALT activities increased and serum AST, LDH, and GGT activities decreased. As a result, the present study indicates that ViCESe because of their antioxidant activity against ethanol damage have a protective effect on the liver.     

Simvastatin and vitamin E effects on cardiac and hepatic oxidative stress in rats fed on high fat diet

High fat diet (HFD) is a common cause of metabolic syndrome and type 2 diabetes mellitus. Published data showed that HFD and subsequent dyslipidemia are major triggers for oxidative stress. Forty-eight male Sprague–Dawley rats, weighing 170–200 g, were divided into six groups: control, control with vitamin E (100 mg/kg/day, i.p.), control with simvastatin (SIM) (10 mg/kg of body weight/day), HFD, HFD with vitamin E, and HFD with SIM. Standard and high cholesterol diets were given for 15 weeks and SIM and vitamin E were added in the last 4 weeks. In all rats, serum vitamin E, total cholesterol (TC), triglycerides (TG), low (LDL) and high (HDL) density lipoproteins, alanine (ALT) and aspartate (AST) transaminases, alkaline phosphatase (ALP), and gamma glutamyl transpeptidase (GGT) as well as cardiac and hepatic thiobarbituric acid-reactive substances (TBARS) and antioxidants (reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT)) were measured. Also, electrocardiogram (ECG) was recorded. HFD significantly increased QTc interval, heart rate (HR), serum TC, TG, LDL, ALT, AST, ALP, GGT, liver TG, and cardiac and hepatic TBARS but decreased antioxidants and HDL, while SIM decreased HR, liver TG, serum TC, TG, and LDL and increased HDL in HFD rats. Vitamin E had no effect. Moreover, SIM and vitamin E decreased QTc interval, serum ALT, AST, ALP, GGT, and cardiac and hepatic TBARS and increased antioxidants in HFD rats. Histopathological observations confirm the biochemical parameters. SIM and vitamin E slow progression of hypercholesterolemia-induced oxidative stress in liver and heart and improve their functions.     

Aflatoxin induced hepatocarcinogenesis in ducks

To assess the carcinogenic response of duck hepatic tissue, an experimental study was undertaken. Pure aflatoxin B₁, was administered to twelve white pekin ducks of two to three months of age at a dose rate of 0.04165 mg/kg body weight every third day for six months. There was reduction in body weight and haemoglobin level from the third month onwards. Total serum protein, albumin and globulin had a slow and gradual reduction and ESR was significantly increased from the third month. Serum enzymes (AST, ALT, GGT and ALP) were significantly increased from the Vlllth to XVth fortnights (Two weeks). Ten ducks developed hepatic tumours by 180th day. Four of them had neoplastic nodules on the 90th day. Histo-pathologically they were hepatocellular carcinoma (6), Cholangiocellular carcinoma (4) and Chronic hepatitis (2). There was moderate to severe expression of GGT and ALP in the liver tissue during neoplastic transformation.     

Ameliorative effect of resveratrol against cymoxanil-mancozeb induced toxicity in rats

This study was conducted to evaluate the cymoxanil-mancozeb (CM) toxicity and investigate the ameliorative effect of resveratrol (Res) against cymoxanil-mancozeb toxicity. Forty rats were divided into four groups; the first group was used as a control group, the second group was exposed to Res only at a dose of 20 mg/kg body weight for 4 weeks, and the third group was administered CM only at a dose of 799 mg/kg body weight for 4 weeks, The fourth group was co-treated with Res+CM for 4 weeks. Blood samples were analyzed for hematological and biochemical parameters. The comet assay was done on liver and blood specimens and histopathological examinations of the liver and intestine. The results demonstrated that CM exposure caused a significant increase in WBCs, lymphocytes, granulocytes, monocytes ALT, AST, ALP, and GGT, and total cholesterol and triglycerides levels accompanied by a decrease in HGB, HCT, RBCs and MCV, MCH, MCHC, HDL and glucose levels with no significant DNA damage in liver and blood. CM mixture induced severe pathological changes in small intestine and liver. Co-treatment of Res with CM improved hematological picture, lipid and glucose profiles also liver enzymes and decreased changes in the architecture of the liver and intestine.     

牛樟芝提取物调控Nrf2/HO-1通路对酒精性肝损伤的保护作用

研究不同剂量（100、200和400mg/kg）的牛樟芝水提物（WE）、醇提后水提取物（WEE）和醇提物（EE）对酒精诱导的ICR小鼠急性肝损伤的保护作用和对Nrf2/HO-1抗氧化信号通路的影响。研究结果表明：与模型组比较,400mg/kg的WE和WEE均能显著抑制血清ALT和AST水平的升高,200mg/kg的WE和WEE分别显著降低血清ALT和AST含量。各剂量的WE、WEE和EE均能显著降低肝脏MDA含量,200和400mg/kg的WE和不同剂量的WEE均可明显提高肝脏的SOD和CAT活力。H&E染色结果表明WE、WEE和EE对酒精诱导的肝损伤均有一定的改善作用,EE处理组的效果相对较差。免疫组化染色结果表明各剂量的WE、WEE和EE均能促进Nrf2的核转位,诱导HO-1的表达,提高肝脏的抗氧化能力,对酒精诱导的急性肝损伤具有明显的保护作用。提示牛樟芝能通过调节Nrf2/HO-1抗氧化信号通路发挥解酒保肝功效。     

Time dependent study to evaluate the efficacy of zinc on hepatic marker enzymes and elemental profile in serum and liver of protein deficient rats

This study was designed to determine the time dependent protective effects of zinc sulfate on the serum and liver marker enzymes along with elemental profile in protein deficient Sprauge Dawley (S.D.) female rats. Zinc sulfate in the dose of 227 mg/l in drinking water was administrated to normal control as well as protein deficient rats for a total duration of 8 weeks. The effects of different treatments were studied on enzymes like alkaline phosphatase (ALP), aspartate aminotransferases (AST) and alanine aminotransferases (ALT) in rat serum at different time intervals of 1, 2, 4 and 8 weeks and in the rat liver at the end of study. The status of different essential elements in liver was also studied. The serum ALP activity got significantly depressed when estimated at the intervals of 4 and 8 weeks. Activity of serum ALT was significantly increased after 4 weeks interval in protein deficient rats and the increasing trend continued upto 8 weeks of protein deficiency. On the other hand, activity of AST showed a significant increase just after 2 weeks and activity continued to be increased up to 8 weeks. Moreover activities of all the hepato marker enzymes showed a significant increase in liver of protein deficient rats. Interestingly, supplementation of Zn to protein deficient rats helped in regulating the altered activities of ALP, AST and ALT both in serum and liver. However, zinc treatment alone to normal rats did not indicate any significant change in the activities of all the enzymes in liver as well serum except at the interval of 2 weeks where a marginal increase in the activity of AST was seen. It has also been observed that concentrations of zinc, copper, iron and selenium were found to be decreased significantly in protein deficient animals. However, the levels of these elements came back to within normal limits when zinc was administrated to protein deficient rats. Published online December 2004