The antioxidant and antifibrogenic effects of the glycosaminoglycans hyaluronic acid and chondroitin-4-sulphate in a subchronic rat model of carbon tetrachloride-induced liver fibrogenesis

Hepatic fibrosis involves the interplay of many factors including reactive oxygen species. Recent reports described antioxidant properties of glycosaminoglycans (GAGs). Since several findings have shown that hyaluronic acid (HYA) and chondroitin-4-sulphate (C4S) may act as antioxidant molecules, the aim of this research was to evaluate the antioxidant effects of HYA and C4S treatment in a rat model of liver fibrosis. The effect on tissue inhibitors of metalloproteinases (TIMPs) was also studied. Liver fibrosis was induced in rats by eight intraperitoneal injections of CCl4, twice a week for 6 weeks. HYA or C4S alone (25 mg/kg) or HYA and C4S in combination (12.5 + 12.5 mg/kg) were administered daily by the same route during the 6 weeks. At the end of the 6-week treatment period (24 h after the last dose of GAGs), the following parameters were evaluated: (1) serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, as index of hepatic cell disruption; (2) hepatic conjugated dienes (CD), as index of lipid peroxidation; (3) hepatic TIMPs activity and expression; (4) hepatic superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity, as index of endogenous defences; (5) hepatic hydroxyproline, as index of collagen deposition. CCl4-induced liver fibrosis enhanced lipid peroxidation and TIMPs activation, increased ALT and AST, depleted antioxidants SOD and GPx, and caused collagen deposition in liver tissue. Treatment with GAGs, especially when in combination, successfully reduced ALT and AST rise, lipid peroxidation by evaluating conjugated dienes, TIMPs activation and mRNA expression, partially restored SOD and GPx activities, and limited collagen deposition in the hepatic tissue. The data obtained showed that these molecules were able to limit hepatic injury induced by chronic CCl4 intoxication and especially limited liver fibrosis. They also confirm that HYA and C4S may exert antioxidant mechanism, while reduction of TIMPs expression suggests that GAGs may influence MMPs and TIMPs imbalance in liver fibrosis.     

Effect of magnesium deficiency on the metabolism of glycosamino-glycans in rats

Magnesium deficiency in rats has significant effect on the concentration of different glycosaminoglycans in the tissues, the nature of the change being different in different tissues. Total glycosaminoglycans, chondroitin-4-sulphate + chondroitin-6-sulphate and dermatan sulphate increased in the aorta while hyaluronic acid, heparan sulphate and heparin decreased. In the liver, total glycosaminoglycans, hyaluronic acid, chondroitin-4-sulphate + 6-sulphate and heparin decreased while total glycosamino-glycans and all the glycosaminoglycan fractions increased in the heart. In the kidney, total glycosaminoglycans showed no significant alteration, hyaluronic acid and heparin decreased while chondroitin-4-sulphate + 6-sulphate increased. Activity of biosynthetic enzymesviz. glucosamine-o-phosphate isomerase and UDPG-dehydrogenase showed decrease in the liver. The concentration of 3’-phosphoadenosine 5’-phosphosulphate, activity of sulphate activating system and sulphotransferase were also similarly altered in the liver in magnesium deficiency.     

17β-Estradiol protects against acetaminophen-overdose-induced acute oxidative hepatic damage and increases the survival rate in mice

Acetaminophen overdose causes acute liver injury or even death in both humans and experimental animals. We investigated the effect of 17β-estradiol against acetaminophen-induced acute liver injury and mortality in mice. Male mice were given acetaminophen (p-acetamidophenol; 300 mg/kg; orally) to induce acute liver injury. Acetaminophen significantly increased the levels of aspartate transaminase, alanine transaminase, myeloperoxidase, lipid peroxidation, and glutathione reductase, but it decreased superoxide dismutase, catalase, and glutathione. In addition, acetaminophen-induced mortality began 4h post-treatment, and all mice died within 9h. 17β-Estradiol (200 μg/kg; i.p.) protected against acetaminophen-induced oxidative hepatic damage by inhibiting neutrophil infiltration and stimulating the antioxidant defense system. However, 17β-estradiol did not affect acetaminophen-induced glutathione depletion or increased glutathione reductase activity. We conclude that 17β-estradiol specifically attenuates acute hepatic damage and decreases mortality in acetaminophen-overdosed male mice.     

Modulatory effect of sesamol on DOCA-salt-induced oxidative stress in uninephrectomized hypertensive rats

The present study was undertaken to investigate the antihypertensive and antioxidant effects of sesamol on uninephrectomized deoxycorticosterone acetate (DOCA)-salt-induced hypertensive rats. Hypertension was induced in surgically single-kidney-removed (left) adult male albino Wistar rats, weighing 180–200 g, by injecting DOCA (25 mg/kg BW) subcutaneously twice a week for 6 weeks, with saline instead of tap water for drinking. Rats were treated with three different doses of sesamol (50, 100 and 200 mg/kg BW) post-orally by gavage daily for 6 weeks. Hypertension was revealed by increased systolic and diastolic blood pressure and the toxicity of DOCA-salt was determined using hepatic marker enzymes, aspartate aminotransferase, alanine aminotransferase, alkaline phospatase and gamma-glutamyl transpeptidase; and, lipid peroxidative markers, thiobarbituric acid reactive substances, lipid hydroperoxides and conjugated dienes were assayed. The activities of enzymatic antioxidants, superoxide dismutase, catalase and glutathione peroxidase and the levels of non-enzymatic antioxidants (vitamin C, vitamin E and reduced glutathione) were evaluated in erythrocytes, plasma and tissues. Post-oral administration of sesamol at the dosage of 50 mg/kg BW remarkably decreased systolic and diastolic blood pressure, hepatic marker enzyme activities and lipid peroxidation products and also enhanced the antioxidant activity. The biochemical observations were also supported by histopathological examinations of the rat liver, kidney and heart sections. These results suggest that sesamol possesses antihypertensive and antioxidant effects.     

Protective effect of pinitol against D-galactosamine-induced hepatotoxicity in rats fed on a high-fat diet

The protective effect of pinitol against D-galactosamine (GalN)-induced liver damage was examined. Forty male Sprague-Dawley rats were divided into normal control, GalN control, and pinitol groups (0.5%, 1%, and 2%). After 8 weeks of feeding, a single dose of GalN (650 mg/kg) was administered 24 h before their sacrifice. The serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and tumor necrosis factor-alpha (TNF-alpha) levels were significantly increased after an injection with GalN (P<0.05), but pinitol supplementation at the level of 0.5% reversed these changes to normal levels. Significant decreases in serum triglyceride and cholesterol and increases in hepatic cholesterol were observed in GalN-intoxicated rats. However, supplementation with pinitol significantly attenuated these trends. In addition, pinitol elevated the Mn-superoxide dismutase, glutathione reductase, and catalase activities, prevented hepatic lipid peroxidation, and restored the hepatic GSH levels and cytochrome P450 2E1 function. Thus, 0.5% pinitol supplementation protected the rats from the hepatotoxicity induced by GalN, at least part of its effect being attributable to attenuation of the oxidative stress and inflammatory process promoted by GalN.     

Effect of vitamin E on monosodium glutamate induced hepatotoxicity and oxidative stress in rats

Monosodium glutamate (MSG), administered to rats (by gavage) at a dose of 0.6 mg/g body weight for 10 days, significantly (P<0.05) induced lipid peroxidation (LPO), decreased reduced glutathione (GSH) level and increased the activities of glutathione-s-transferase (GST), catalase and superoxide dismutase (SOD) in the liver of the animals; these were observed 24 hr after 10 days of administration. The activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma glutamyl transferase (GGT) were also significantly increased in the serum, on MSG administration. Vitamin E (0.2 mg/g body wt) co-administered with MSG, significantly reduced the LPO, increased the GSH level and decreased the hepatic activities of GST, catalase and SOD. The activities of ALT, AST and GGT in the serum were also significantly reduced. The results showed that MSG at a dose of 0.6 mg/g body wt induced the oxidative stress and hepatotoxicity in rats and vitamin E ameliorated MSG-induced oxidative stress and hepatotoxicity.     

Effects of Dietary Supplementation with Vitamin C and Vitamin E and Their Combination on Growth Performance,Some Biochemical Parameters,and Oxidative Stress Induced by Copper Toxicity in Broilers

This study investigated effects of dietary supplementation with vitamin C, vitamin E on performance, biochemical parameters, and oxidative stress induced by copper toxicity in broilers. A total of 240, 1-day-old, broilers were assigned to eight groups with three replicates of 10 chicks each. The groups were fed on the following diets: control (basal diet), vitamin C (250 mg/kg diet), vitamin E (250 mg/kg diet), vitamin C + vitamin E (250 mg/kg?+?250 mg/kg diet), and copper (300 mg/kg diet) alone or in combination with the corresponding vitamins. At the 6th week, the body weights of broilers were decreased in copper, copper + vitamin E, and copper + vitamin C + vitamin E groups compared to control. The feed conversion ratio was poor in copper group. Plasma aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase activities, iron, copper concentrations, and erythrocyte malondialdehyde were increased; plasma vitamin A and C concentrations and erythrocyte superoxide dismutase were decreased in copper group compared to control. Glutathione peroxidase, vitamin C, and iron levels were increased; aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and copper levels were decreased in copper + vitamin C group, while superoxide dismutase, glutathione peroxidase, and vitamin E concentrations were increased; aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase were decreased in copper with vitamin E group compared to copper group. The vitamin C concentrations were increased; copper, uric acid, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and malondialdehyde were decreased in copper + vitamin C + vitamin E group compared to copper group. To conclude, copper caused oxidative stress in broilers. The combination of vitamin C and vitamin E addition might alleviate the harmful effects of copper as demonstrated by decreased lipid peroxidation and hepatic enzymes.     

The protective effects of Curcuma longa Linn. extract on carbon tetrachloride-induced hepatotoxicity in rats via upregulation of Nrf2

This study was designed to investigate the potentially protective effects of Curcuma longa Linn. extract (CLE) on carbon tetrachloride (CCl4)-induced hepatotoxicity in rats. Male Sprague-Dawley rats were pretreated with 50 or 100mg/kg of CLE or 100mg/kg of butylated hydroxytoluene (BHT) for 14 days before CCl4 administration. In addition, the CLE control group was pretreated with 100mg/kg CLE for only 14 days. Three hours after the final treatment, a single dose of CCl4 (20mg/kg) was administrated intraperitoneally to each group. After the completion of this phase of the experiment, food and water were removed 12 h prior to the next step. The rats were then anesthetized by urethane and their blood and liver were collected. It was observed that the aspartate aminotransferase and alanine aminotransferase activities of the serum, and the hepatic malondialdehyde levels had significantly decreased in the CLE group when compared with the CCl4-treated group. The antioxidant activities, such as superoxide dismutase, catalase, and glutathione peroxidase activities, in addition to glutathione content, had increased considerably in the CLE group compared with the CCl4-treated group. Phase II detoxifying enzymes, such as glutathione S-transferase, were found to have significantly increased in the CLE group as opposed to the CCl4-treated group. The content of Nrf2 was determined by Western blot analysis. Pretreated CLE increased the level of nuclear translocated Nrf2, and the Nrf2 then increased the activity of the antioxidant and phase II detoxifying enzymes. These results indicate that CLE has protective effects against CCl4-induced hepatotoxicity in rats, via activities of antioxidant and phase II detoxifying enzymes, and through the activation of nuclear translocated Nrf2.     

Antioxidant DL-alpha lipoic acid as an attenuator of adriamycin induced hepatotoxicity in rat model

Protective efficacy of DL-alpha lipoic acid on adriamycin induced hepatotoxicity was evaluated in rats. Adriamycin toxicity, induced by a single injection (ip; 15 mg/kg body wt), was expressed by an elevation in alanine transaminase, aspartate transaminase, bilirubin levels in serum and alkaline phosphatase, lactate dehydrogenase, alanine transaminase, aspartate transaminase activity in hepatic tissue. Adriamycin produced significant increase in malondialdehyde levels indicating tissue lipid peroxidation and potentially inhibiting the activity of antioxidant, reduced glutathione and antioxidant enzymes, catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, glucose-6-phosphate dehydrogenase. The present results showed that pretreatment with lipoic acid [75 mg/kg body wt/day (ip), 24 h prior to administration of adriamycin] significantly restored various cellular activity suggesting the antioxidant potential of lipoic acid in ameliorating the hepatotoxicity induced by adriamycin.     

Hepatoprotective Effect of Wheat-Based Solid-State Fermented Antrodia cinnamomea in Carbon Tetrachloride-Induced Liver Injury in Rat

Antrodia cinnamomea (A. cinnamomea) is an indigenous medical fungus in Taiwan and has multiple biological functions, including hepatoprotective and immune-modulatory effects. Currently, the commercially available A. cinnamomea are mainly liquid- and solid-state fermented A. cinnamomea. However, the hepatoprotective effect of solid-state fermented A. cinnamomea has never been reported. Here we evaluate the ability of air-dried, ground and non-extracted wheat-based solid-state fermented A. cinnamomea (WFAC) to protect against carbon tetrachloride (CCl₄)-induced hepatic injury in vivo. The results showed that oral administration of WFAC dose dependently (180, 540 and 1080 mg/kg) ameliorated the increase in plasma aspartate aminotransferase and alanine aminotransferase levels caused by chronic repeated CCl₄ intoxication in rats. WFAC significantly reduced the CCl₄-induced increase in hepatic lipid peroxidation levels and hydroxyproline contents, as well as reducing the spleen weight and water content of the liver. WFAC also restored the hepatic soluble protein synthesis and plasma albumin concentration in CCl₄-intoxicated rats, but it did not affect the activities of superoxide dismutase, catalase, or glutathione peroxidase. In addition, a hepatic morphological analysis showed that the hepatic fibrosis and necrosis induced by CCl₄ were significantly ameliorated by WFAC. Furthermore, the body weights of control rats and WFAC-administered rats were not significantly different, and no adverse effects were observed in WFAC-administered rats. These results indicate that WFAC is a nontoxic hepatoprotective agent against chronic CCl₄-induced hepatic injury.     

Modification of hepatic vitamin E stores in vivo. I. Alterations in plasma and liver vitamin E content by methyl ethyl ketone peroxide

Since experiments with freshly isolated rat hepatocytes have shown that cellular vitamin E is consumed in response to insult by compounds that induce an oxidative stress only after cellular glutathione (GSH) concentrations have been substantially depleted, experiments were performed to determine whether this sequence of events occurred in response to oxidative insult in vivo. The role that plasma vitamin E plays in the response to chemically induced oxidative injury in vivo was also assessed. Treatments with 40 mg/kg of methyl ethyl ketone peroxide (MEKP) quickly induced lipid peroxidation in vivo and from one to 4 h after treatment caused a depression in the plasma content of vitamin E and the liver content of GSH, as well as signs of toxicity (elevations in serum activities of alanine and aspartate aminotransferases). At these time points however, the liver content of vitamin E was either indistinguishable from or slightly elevated from controls. By 12 to 24 h after treatment the liver content of vitamin E was reduced by 20-25% whereas values for all other indicators had returned toward control levels. Pretreatment of rats with L-buthionine-S,R-sulfoximine, an inhibitor of GSH by 4 or 24 h after treatment, did not alter the time course or extent of hepatic vitamin E depletion that was observed after treatment with MEKP. Other compounds that induce oxidative stress and lipid peroxidation to the liver, carbon tetrachloride and menadione, did not provoke an alteration in hepatic vitamin E levels as compared to controls 1 day after treatment. These findings indicate that depletion of hepatic vitamin E may not occur as an immediate consequence of oxidative insult to the liver and that the depletion of hepatic vitamin E levels may not be related to the extent of prior GSH depletion. Moreover, these findings suggest that alterations in the plasma concentration of vitamin E may not reflect concurrent alterations in hepatic vitamin E levels. A mechanism whereby liver vitamin E stores are mobilized for the maintenance of plasma vitamin E levels is proposed.     

Effect of estragole on glucocorticoid induction of tyrosine aminotransferase and tryprophan oxygenase in the rat and mouse liver

A single intraperitoneal injection of Estragole (300 mg/kg) to female ICR mice 19 hours prior to Dexamethasone induction decreased induced activities of tyrosine aminotransferase (TAT) and tryptophan oxygenase (TO) nearly to 50% of the control values. In these mice, activities of the marker enzymes of liver damage: alanine aminotransferase (ALAT) and aspartate aminotransferase (AAT) increased in the blood 1.7-2.3-fold as compared with the untreated controls. By contrast, carbon tetrachloride (100 mg/kg) increased the blood AIAT and AsAT activities 135- and 30-fold as compared with the control, but inhibited the TAT and TO induction much less than Estragole did. Estragole seems to inhibit the glucocorticoid induction of these hepatic enzymes not via the unspecific toxic damage of the liver.     

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.     

Hepatoprotective effect of a protein-enriched fraction from the maggots (Musca domestica) against CCl4-induced hepatic damage in rats

The hepatoprotective potential of a protein-enriched fraction (PEF) isolated from the maggots of housefly (Musca domestica) was evaluated in rats against carbon tetrachloride (CCl₄)-induced acute hepatic damage. Activities of serum aspartate aminotransferase and alanine aminotransferase increased by 4- and 13-fold induced by CCl₄, were significantly inhibited by pretreatment with 50, 100 and 200 mg PEF/kg. The formation of malondialdehyde was also significantly decreased in PEF-treated group compared with CCl₄-treated group. The treatments with PEF also elevated total protein levels significantly. These results were further supplemented by histopathological examination of liver sections. Hyperplasia of kupffer cells was observed after treatment with PEF (100 and 200 mg/kg). We conclude that PEF is effective in this model of liver damage.     

The Redox Status in Rats Treated with Flaxseed Oil and Lead-Induced Hepatotoxicity

Lead is a persistent environmental pollutant, and its toxicity continues to be a major health problem due to its interference with natural environment. In the present study, we have evaluated the effect of flaxseed oil on lead acetate-mediated hepatic oxidative stress and toxicity in rats. Lead acetate enhanced lipid peroxidation and nitric oxide production in both serum and liver with concomitant reduction in glutathione, catalase, superoxide dismutase, glutathione reductase, glutathione-S-transferase, and glutathione peroxidase activities, these findings were associated with DNA fragmentation. In addition, lead acetate caused liver injury as indicated by histopathological changed of the liver with an elevation in total bilirubin, serum alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transpeptidase, and alkaline phosphatase. Treatment of rats with flaxseed oil resulted in marked improvement in most of the studied parameters as well as histopathological features. On the basis of the above results it can hypothesized that flaxseed oil is a natural product can be protect against lead acetate-mediated hepatic cytotoxicity.     

Protective Effects of Polydatin from Polygonum cuspidatum against Carbon Tetrachloride-Induced Liver Injury in Mice

Polydatin is one of main compounds in Polygonum cuspidatum, a plant with both medicinal and nutritional value. The possible hepatoprotective effects of polydatin on acute liver injury mice induced by carbon tetrachloride (CCl₄) and the mechanisms involved were investigated. Intraperitoneal injection of CCl₄ (50 µl/kg) resulted in a significant increase in the levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and hepatic malondialdehyde (MDA), also a marked enhancement in the expression of hepatic tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and nuclearfactor-kappa B (NF-κB). On the other hand, decreased glutathione (GSH) content and activities of glutathione transferase (GST), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were observed following CCl₄ exposure. Nevertheless, all of these phenotypes were evidently reversed by preadministration of polydatin for 5 continuous days. The mRNA and protein expression levels of hepatic growth factor-beta1 (TGF-β₁) were enhanced further by polydatin. These results suggest that polydatin protects mice against CCl₄-induced liver injury through antioxidant stress and antiinflammatory effects. Polydatin may be an effective hepatoprotective agent and a promising candidate for the treatment of oxidative stress- and inflammation-related diseases.     

Optimization of extraction, preliminary characterization and hepatoprotective effects of polysaccharides from Stachys floridana Schuttl. ex Benth

Optimization of extraction, preliminary characterization and hepatoprotective activity of polysaccharides from Stachys flordana Schuttl. ex Benth. (SFPS) were investigated in the present study. Firstly, the optimal conditions for extraction of SFPS were obtained by a Box-Behnken design as follows: extraction temperature 94 °C, extracting time 4 h and ratio of water to material 19 mg/ml. Then, the analysis of monosaccharide composition by gas chromatography revealed that SFPS was composed of rhamnose, arabinose, glucose and galactose in a molar percent of 2.05, 9.16, 28.66 and 60.14, respectively. Finally, we demonstrated that SFPS had a significant protective effect against acute hepatotoxicity induced by carbon tetrachloride (CCl₄) in mice, as evident by lower levels of serum alanine aminotransferase, aspartate aminotransferase and hepatic malondialdehyde, higher activities of superoxide dismutase and catalase, as well as higher reduced glutathione concentration compared to the CCl₄-treated group. The results suggested that SFPS could be explored as novel natural supplement.     

Acute liver damage induced by 2-nitropropane in rats: effect of diphenyl diselenide on antioxidant defenses

The effect of post-treatment with diphenyl diselenide on liver damage induced by 2-nitropropane (2-NP) was examined in male rats. Rats were pre-treated with a single dose of 2-NP (100 mg/kg body weight dissolved in canola oil). Afterward, the animals were post-treated with a dose of diphenyl diselenide (10, 50 or 100 micromol/kg). The parameters that indicate tissue damage such as liver histopathology, plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), urea and creatinine were determined. Since the liver damage induced by 2-NP is related to oxidative damage, lipid peroxidation, superoxide dismutase (SOD), catalase (CAT) and ascorbic acid level were also evaluated. Diphenyl diselenide (50 and 100 micromol/kg) effectively restored the increase of ALT and AST activities and urea level when compared to the 2-NP group. At the higher dose, diphenyl diselenide decreased GGT activity. Treatment with diphenyl diselenide, at all doses, effectively ameliorated the increase of hepatic and renal lipid peroxidation when compared to 2-NP group. 2-NP reduced CAT activity and neither alter SOD activity nor ascorbic acid level. This study points out the involvement of CAT activity in 2-NP-induced acute liver damage and suggests that the post-treatment with diphenyl diselenide was effective in restoring the hepatic damage induced by 2-NP.     

Protective effects of thymoquinone and desferrioxamine against hepatotoxicity of carbon tetrachloride in mice

The effects of thymoquinone (TQ) and desferrioxamine (DFO) against carbon tetrachloride (CCl4)-induced hepatotoxicity were investigated. A single dose of CCl4 (20 microl/kg, i.p.) induced hepatotoxicity, manifested biochemically by significant elevation of activities of serum enzymes, such as alanine transaminase (ALT, EC: 2.6.1.2) , aspartate transaminase (AST, EC: 2.6.1.1) and lactate dehydrogenase (LDH, EC: 1.1.1.27). Hepatotoxicity was further evidenced by significant decrease of total sulfhydryl (-SH) content, and catalase (EC: 1.11.1.6) activity in hepatic tissues and significant increase in hepatic lipid peroxidation measured as malondialdhyde (MDA). Pretreatment of mice with DFO (200 mg/kg i.p.) 1 h before CCl4 injection or administration of TQ (16 mg/kg/day, p.o.) in drinking water, starting 5 days before CCl4 injection and continuing during the experimental period, ameliorated the hepatotoxicity induced by CCl4, as evidenced by a significant reduction in the elevated levels of serum enzymes as well as a significant decrease in the hepatic MDA content and a significant increase in the total sulfhydryl content 24 h after CCl4 administration. In a separate in vitro assay, TQ and DFO inhibited the non-enzymatic lipid peroxidation of normal mice liver homogenate induced by Fe3+/ascorbate in a dose-dependent manner. These results indicate that TQ and DFO are efficient cytoprotective agents against CCl4-induced hepotoxicity, possibly through inhibition of the production of oxygen free radicals that cause lipid peroxidation.