Antioxidative effect of chitosan on chronic carbon tetrachloride induced hepatic injury in rats

Carbon tetrachloride (CCl(4)) is a toxic material known to induce lipid peroxidation and liver damage. To determine if chitosan has antioxidative effects on CCl(4)-induced liver injury, we administered 1 ml/kg of CCl(4) resolved in a 50% corn oil solution to rats every week by intraperitoneal injection. Chitosan (200 mg/kg body weight per day, MW 380,000 Da) was administered to the CCl(4) + chitosan treated rats by oral gavage during the experimental period. Chitosan significantly decreased liver thiobarbituric acid reactive substances (TBARS) and increased antioxidant enzyme activities (catalase and superoxide dismutase (SOD)). Fatty acid composition was not remarkably changed by chitosan; only arachidonic acid (20:4n-6) levels were significantly altered by CCl(4). Chitosan administration in the present experiment did not restore the decreased delta5-desaturase activity. In addition, chitosan supplementation did not prevent the CCl(4) induced degradation of CYP2E1. In conclusion, our results suggest that chitosan has antioxidative but not detoxifying effects on chronic CCl(4) induced hepatic injury in rats.     

The effect of chondroitin sulfate against CCl4-induced hepatotoxicity

This study was conducted to develop a new biomaterial to be used for an antioxidative drug. In this study, the hepatoprotective effect of chondroitin sulfate (CS) (100 mg/kg and 200 mg/kg body weight) was investigated at the antioxidative enzyme levels of liver total homogenate and mitochondria fraction. And the carbone tetrachloride (CCl(4))-induced rats were used as hepatotoxic models. The CCl(4) induced rat has been widely used as a hepatotoxic model due to its practicality, convenience and cost effectiveness since the generation of free oxygen radicals by CCl(4) injection was proposed as an important causative agent of hepatotoxicity. Malondialdehyde (MDA) levels were determined as well as the activities of superoxide dismutase (SOD), catalase (CAT), reduced-glutathione (GSH), oxidized-glutathione (GSSG) and glutathione peroxidase (GPx) in the liver. In addition, histopathology of liver tissue was investigated. Liver antioxidative enzyme activity was elevated while MDA concentration was decreased in all CS treated animals. The results demonstrated that CS protected oxidative stress in a dose dependent manner. Moreover, inflammation and cirrhosis in liver tissue of CS treated group were significantly decreased. It gave us an impression that CS might be a radical scavenger.     

Ameliorative effect of ajwain extract on hexachlorocyclohexane-induced lipid peroxidation in rat liver

Effect of ajwain extract on hexachlorocyclohexane-induced oxidative stress and toxicity in rats were investigated. Six groups of rats were maintained for 12 weeks as (1) Control; (2) HCH (300 mg/kg body weight) injected (3) 1% ajwain extract incorporated diet (4)1% ajwain extract incorporated diet + HCH (5) 2% ajwain extract incorporated diet and (6) 2% ajwain extract incorporated diet + HCH. Results revealed that HCH administration lead to an increase in hepatic lipid peroxidation associated with reduction in, levels of glutathione (GSH), activity of superoxide dismutase (SOD), catalase and glucose-6-phosphate dehydrogenase. Prefeeding of ajwain extract resulted in decreased hepatic levels of lipid peroxides and increased GSH, GSH-peroxidase, G-6-PDH, SOD, catalase and glutathione S-transferase (GST) activities. At the same time there was a significant reduction in hepatic levels of HCH-induced raise in lipid peroxides as a result of the prefeeding the extract. Prefeeding of ajwain extract at 1% level to rats injected with HCH reverted the significant changes in catalase, G-6-PDH, GST and -glutamyl transpeptidase. HCH-induced formation of micronuclei in femur bone marrow was also reduced significantly. It was concluded that HCH administration resulted in hepatic free radical stress, causing toxicity, which could be reduced by the dietary ajwain extract.     

Ameliorative effect Trichosanthes dioica root against experimentally induced arsenic toxicity in male albino rats

The present study evaluated the ameliorative potential of hydroalcoholic extract of Trichosanthes dioica root (TDA) against arsenic induced toxicity in male albino rats. TDA (5 and 10mg/kg) was administered orally to rats for 20 consecutive days before oral administration of sodium arsenite (10mg/kg) for 8 days. Then the body weights, organ weights, haematological profiles, serum biochemical profile; hepatic and renal antioxidative parameters viz. lipid peroxidation, reduced and oxidized glutathione, glutathione-S-transferase, glutathione peroxidase, glutathione reductase, superoxide dismutase, catalase and DNA fragmentation were evaluated. Pretreatment with TDA markedly and significantly normalized body weights, organ weights, haematological profiles, serum biochemical profile and significantly modulated all the hepatic and renal biochemical parameters and reduced DNA fragmentation in arsenic intoxicated rats. The present findings conclude that T. dioica root possessed remarkable ameliorative effect against arsenic induced organ toxicity in male albino rats mediated by alleviation of arsenic induced oxidative stress by multiple mechanisms.     

Hepatoprotective potential of polyphenol rich extract of Murraya koenigii L.: an in vivo study

The present study investigates hepatoprotective effects of polyphenol rich Murraya koenigii L. (MK) hydro-ethanolic leaf extract in CCl(4) treated hepatotoxic rats. Plasma markers of hepatic damage, lipid peroxidation levels, enzymatic, and non-enzymatic antioxidants in liver and histopathological changes were investigated in control and treated rats. MK pretreated rats with different doses (200, 400 and 600mg/kg body weight) showed significant decrement in activity levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total protein, and bilirubin. Also, MK treated rats recorded a dose dependent increment in hepatic super oxide dismutase, catalase, reduced glutathione and ascorbic acid and, a decrement in lipid peroxidation. Microscopic evaluations of liver revealed CCl(4)-induced lesions and related toxic manifestations that were minimal in liver of rats pretreated with MK extract. These results demonstrate that hydro-ethanolic leaf extract of MK possesses hepatoprotective potentials.     

Hepatoprotective Role of Zinc in Lead-Treated,Protein-Deficient Rats

The current study was designed to evaluate the hepatoprotective role of zinc after lead (Pb) treatment of protein-deficient (PD) rats. The animals were subjected to seven different treatment groups: G-1 (normal control, 18% protein), G-2 (protein-deficient, 8% protein), G-3 (Pb-treated, 100 mg/kg body weight of lead acetate), G-4 (Zn-treated, zinc sulfate at a dose level of 227 mg/L drinking water), G-5 (PD + Pb-treated), G-6 (PD + Zn-treated), and G-7 (PD + Pb + Zn-treated). Serum albumin levels and total serum protein contents were estimated to assess the severity of protein deficiency at the end of 8 weeks in all the treatment groups. Also, the study explored the role of zinc on antioxidative defense system enzymes in liver of protein-deficient rats subjected to lead toxicity treatment. Further, the study was extended to elucidate the levels of zinc and lead in liver tissue after different treatments of rats using positron-induced X-ray emission technique (PIXE). The current study indicated a significant change in the levels of various antioxidative enzymes and serum albumin as well as total protein contents of protein-deficient rats subjected to lead treatment. A significant increase in the levels of malondialdehyde (MDA), catalase, and glutathione peroxidase (GPx) was seen after 8 weeks of lead treatment of protein-deficient rats. On the contrary, levels of albumin, total protein content, superoxide dismutase (SOD), GSH, were found to be decreased. Interestingly, zinc supplementation has tended to normalize the altered levels of these enzymes to a significant extent. The levels of zinc in liver tissue was found to be decreased significantly in protein-deficient as well as lead-treated rats. However, hepatic zinc concentration was increased to a significant extent in protein-deficient rats supplemented with zinc when compared with protein-deficient rats. Further, the presence of lead was also observed in livers of lead-treated animals. In conclusion, the study revealed the antioxidative role of zinc in hepatotoxic conditions induced by subjecting the rats to protein-deficient diet and lead treatment.     

Hepatoprotective role of zinc in lead-treated, protein-deficient rats

The current study was designed to evaluate the hepatoprotective role of zinc after lead (Pb) treatment of protein-deficient (PD) rats. The animals were subjected to seven different treatment groups: G-1 (normal control, 18% protein), G-2 (protein-deficient, 8% protein), G-3 (Pb-treated, 100 mg/kg body weight of lead acetate), G-4 (Zn-treated, zinc sulfate at a dose level of 227 mg/L drinking water), G-5 (PD + Pb-treated), G-6 (PD + Zn-treated), and G-7 (PD + Pb + Zn-treated). Serum albumin levels and total serum protein contents were estimated to assess the severity of protein deficiency at the end of 8 weeks in all the treatment groups. Also, the study explored the role of zinc on antioxidative defense system enzymes in liver of protein-deficient rats subjected to lead toxicity treatment. Further, the study was extended to elucidate the levels of zinc and lead in liver tissue after different treatments of rats using positron-induced X-ray emission technique (PIXE). The current study indicated a significant change in the levels of various antioxidative enzymes and serum albumin as well as total protein contents of protein-deficient rats subjected to lead treatment. A significant increase in the levels of malondialdehyde (MDA), catalase, and glutathione peroxidase (GPx) was seen after 8 weeks of lead treatment of protein-deficient rats. On the contrary, levels of albumin, total protein content, superoxide dismutase (SOD), GSH, were found to be decreased. Interestingly, zinc supplementation has tended to normalize the altered levels of these enzymes to a significant extent. The levels of zinc in liver tissue was found to be decreased significantly in protein-deficient as well as lead-treated rats. However, hepatic zinc concentration was increased to a significant extent in protein-deficient rats supplemented with zinc when compared with protein-deficient rats. Further, the presence of lead was also observed in livers of lead-treated animals. In conclusion, the study revealed the antioxidative role of zinc in hepatotoxic conditions induced by subjecting the rats to protein-deficient diet and lead treatment.     

Oxidative stress induced in PCB 126-exposed northern leopard frogs, Rana pipiens

Northern leopard frogs Rana pipiens exposed to PCB 126 (3,3',4,4',5-pentachlorobiphenyl) were examined for hepatic oxidative stress. In a dose-response study, northern leopard frogs were injected intraperitoneally with either PCB 126 in corn oil (0.2, 0.7, 2.3, or 7.8 mg/kg body weight) or corn oil alone. In a time-course study, frogs received 7.8 mg/kg or corn oil alone, and were examined at 1, 2, 3, and 4 wk after dosing. Hepatic concentrations of reduced glutathione (GSH), thiobarbituric acid-reactive substances (TBARS), and total sulfhydryls (total SH), as well as activities of glutathione peroxidase (GSH-P), GSSG reductase (GSSG-R), glucose-6-phosphate dehydrogenase (G-6-PDH), and glutathione S-transferase (GSH-S-T) were measured. In the dose-response experiment, few effects were apparent 1 wk after dosing. In the time-course experiment, significant changes were observed in the 7.8-mg/kg group at 2 wk or more posttreatment. Hepatic concentrations of GSH and TBARS were higher than in corresponding controls at wk 3 and 4; the activities of GSSG-R and GSH-S-T were higher than in controls at wk 2 and 4; and the activity of G-6-PDH was increased at wk 2 and 4. These data collectively indicate that altered glutathione metabolism and oxidative stress occurred and were indicative of both toxicity and induction of protective mechanisms in frogs exposed to PCB. A similar delay in response was reported in fish and may relate to lower metabolic rate and physiological reactions in ectothermic vertebrates.     

Erythrocyte redox status in streptozotocin diabetic rats: effect of Casearia esculenta root extract

The present study was aimed to investigate the effect of Casearia esculenta root extract on erythrocyte lipid peroxidation and to assess the status of antioxidants in red blood cells of streptozotocin (STZ) diabetic rats. The study showed a significant elevation (p < 0.05) of erythrocyte thiobarbituric acid reactive substances (TBARS), an index of lipid peroxidation and significant reduction (p < 0.05) in reduced glutathione (GSH), ascorbic acid (vitamin C), alpha-tocopherol (vitamin E), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) in the STZ diabetic rats. The study also observed significant reduction in membrane cholesterol and phospholipid content in STZ diabetic rats. By oral administration of C. esculenta (200 and 300 mg/kg body wt.) for 45 days to the diabetic rats these values approached almost normal levels. A dose of 300 mg/kg body weight C. esculenta extract showed better antioxidant effects than 200 mg/kg body weight.     

Tephrosia purpurea ameliorates N-diethylnitrosamine and potassium bromate-mediated renal oxidative stress and toxicity in Wistar rats.

In an earlier communication, we have shown that Tephrosia purpurea ameliorates benzoyl peroxide-induced oxidative stress in murine skin (Saleem et al. 1999). The present study was designed to investigate a chemopreventive efficacy of T purpurea against N-diethylnitrosamine-initiated and potassium bromate-mediated oxidative stress and toxicity in rat kidney. A single intraperitoneal dose of N-diethylnitrosamine (200 mg/kg body weight) one hr prior to the dose of KBrO3 (125 mg/kg body weight) increases microsomal lipid peroxidation and the activity of xanthine oxidase and decreases the activities of renal antioxidant enzymes viz., catalase, glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase, phase II metabolizing enzymes such as glutathione-S-transferase and quinone reductase and causes depletion in the level of renal glutathione content. A sharp increase in blood urea nitrogen and serum creatinine has also been observed. Prophylactic treatment of rats with T. purpurea at doses of 5 mg/kg body weight and 10 mg/kg body weight prevented N-diethylnitrosamine-initiated and KBrO3 promoted renal oxidative stress and toxicity. The susceptibility of renal microsomal membrane for iron ascorbate-induced lipid peroxidation and xanthine oxidase activities were significantly reduced (P<0.01). The depleted levels of glutathione, the inhibited activities of antioxidant enzymes, phase II metabolizing enzymes and the enhanced levels of serum creatinine and blood urea nitrogen were recovered to a significant level (P<0.01). All the antioxidant enzymes were recovered dose-dependently. Our data indicate that T purpurea besides a skin antioxidant can be a potent chemopreventive agent against renal oxidative stress and carcinogenesis induced by N-diethylnitrosamine and KBrO3.     

Comparison of hypoxic cell radiosensitizers,KIN-804, KIN-844, KIN-806 and TX-1877, on brain and liver metabolizing capacities in mice bearing Ehrlich ascites carcinoma

The biochemical effects of the 2-nitroimidazole hypoxic cell radiosensitizers KIN-804, KIN-806, and their analogues KIN-844 and TX-1877 on brain acetylcholinesterase (AChE) and hepatic free radical scavenging systems, such as reduced glutathione (GSH) and glucose-6-phosphate dehydrogenase (G-6-PDH) levels, and hepatic antioxidants, such as superoxide dismutase (SOD) and catalase, were evaluated in Ehrlich ascites carcinoma (EAC)-bearing Swiss albino mice. The assay of brain AChE revealed nonsignificant changes with all drugs examined. To evaluate the hepatic metabolic capacity, groups of mice were divided into control, EAC-inoculated, 10-Gy local gamma-irradiated, and KIN-804, KIN-844, KIN-806, or TX-1877 (50 mg/kg body weight, i.p.) groups, and gamma-irradiation was combined with each drug. EAC inoculation markedly suppressed GSH, G-6-PDH, SOD, and catalase levels. On the other hand, treatment with gamma-irradiation significantly enhanced them. The treatment of EAC-bearing mice with each drug alone in the absence of gamma-irradiation revealed that KIN-806 and its derivative TX-1877 showed antitumor activity through their significant recovery of GSH and SOD levels, respectively, in the EAC-bearing mice group. Similarly, the combined treatment of EAC-bearing mice with gamma-irradiation with each of the drugs tested showed that KIN-806 and TX-1877 significantly increased GSH and SOD, and to a lesser extent G-6-PDH and catalase levels. On the other hand, KIN-804 and KIN-844 had only a nonsignificant effect on all parameters examined. In conclusion, these data reveal that the administration of KIN-806 and TX-1877 with or without subsequent gamma-irradiation, resulted in significant recovery of GSH and SOD activities that were inhibited by EAC inoculation.     

Abrogation of potassium bromate-induced renal oxidative stress and subsequent cell proliferation response by soy isoflavones in Wistar rats

Potassium bromate (KBrO3) is a potent nephrotoxic agent. In this study, we show the modulatory effect of soy isoflavones on KBrO3-mediated renal oxidative stress and subsequent cell proliferation response in Wistar rats. KBrO3 (125 mg/kg body weight, intraperitoneally) caused reduction in renal glutathione content, activities of renal anti-oxidant enzymes, viz., glutathione peroxidase, glutathione reductase, catalase, glucose-6-phosphate dehydrogenase and phase-II metabolising enzymes such as glutathione-S-transferase and quinone reductase with enhancement in xanthine oxidase, lipid peroxidation, gamma-glutamyl transpeptidase and hydrogen peroxide (H2O2). KBrO3 treatment also induced blood urea nitrogen, serum creatinine and tumor promotion markers, viz., ornithine decarboxylase (ODC) activity and thymidine [3H] incorporation into renal DNA. Treatment of rats orally with soy isoflavones (5 mg/kg body weight and 10 mg/kg body weight) resulted in a significant decrease in xanthine oxidase (P < 0.05), lipid peroxidation, gamma-glutamyl transpeptidase, H2O2 generation, blood urea nitrogen, serum creatinine, renal ODC activity and DNA synthesis (P < 0.001). There was also significant recovery of renal glutathione content (P < 0.01), anti-oxidant enzymes and phase-II metabolising enzymes (P < 0.001). Thus, our results show that soy isoflavones acts as potent chemopreventive agent against KBrO3-mediated renal oxidative stress, toxicity and subsequent cell proliferation response in Wistar rats.     

Eruca sativa seeds possess antioxidant activity and exert a protective effect on mercuric chloride induced renal toxicity.

Mercuric chloride (HgCl(2)) is a well-known nephrotoxic agent. Increasing number of evidences suggest the role of oxidative stress in HgCl(2) induced nephrotoxicity. Eruca sativa is widely used in folklore medicines and has a good reputation as a remedy of renal ailments. In the present study, the antioxidant potential of ethanolic extract of E. sativa seeds was determined and its protective effect on HgCl(2) induced renal toxicity was investigated. The extract was found to possess a potent antioxidant effect, with a large amount of polyphenols and a high reducing ability. HPLC analysis of the extract revealed glucoerucin and flavonoids to be the major antioxidants present in it. E. sativa extract significantly scavenged several reactive oxygen species (ROS) and reactive nitrogen species (RNS). Feeding of the extract to rats afforded a significant protection against HgCl(2) induced renal toxicity. Subcutaneous administration of 4 mg/kg body weight HgCl(2) induced renal injury evident as a marked elevation in serum creatinine and blood urea nitrogen levels, and histopathological changes such as necrosis, oedema and congestion of stroma and glomeruli. Oxidative modulation of renal tissues following HgCl(2) exposure was evident from a significant elevation in lipid peroxidation and attenuation in glutathione (GSH) contents and activities of antioxidant enzymes viz., catalase (CAT), glutathione peroxidase (GPX), superoxide dismutase (SOD) and glutathione reductase (GR). Oral administration of E. sativa extract to rats at a dose regimen: 50-200 mg/kg body weight for 7 days prior to HgCl(2) treatment significantly and dose dependently protected against alterations in all these diagnostic parameters. The data obtained in the present study suggests E. sativa seeds to possess a potent antioxidant and renal protective activity and preclude oxidative damage inflicted to the kidney.     

Protective effect of salvianic acid a on acute liver injury induced by carbon tetrachloride in rats

Previous research has shown that salvianic acid A [2-(3,4-dihydroxyphenyl)-2-hydroxy-propanoic acid, SA] extracted from Salvia miltiorrhiza BGE (Danshen) markedly inhibits lipid peroxidation of mitochondrial membrane of hepatic cells in vitro. The present study was conducted to examine protective effect of SA on liver injury induced by carbon tetrachloride (CCl4) and its possible mechanism in vivo. Male Sprague-Dawley rats weighing 180-200 g were used in the experiments. Five mmol/kg CCl4 in olive oil was given to rats i.p. Spectrophotometrical method was used to measure activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum, activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) as well as malondialdehyde (MDA) level in hepatic tissue and the rate of superoxide anion (O2*-) generation in hepatic submitochondrial particles. Hepatic histological structure was observed under light microscopy. CCl4 caused significant changes of activities of the enzymes, MDA level, and the rate of O2*- generation and histopathological changes of acute hepatic injury were noted. SA reversed the significant changes induced by CCl4. These results demonstrate that SA produces protective action on acute hepatic injury induced by CCl4 via an antioxidative mechanism.     

Carbon tetrachloride-induced nephrotoxicity and DNA damage in rats: Protective role of vanillin

In this study, the protective effects of vanillin were evaluated against carbon tetrachloride (CCl(4))-induced kidney damages in Wistar albino rats. CCl(4) (1 ml/kg, intraperitoneally [i.p.]) caused a significant induction of renal disorder, oxidative damage and DNA fragmentation as evidenced by increased plasma creatinine, urea and uric acid levels, increased lipid peroxidation (malondialdehyde [MDA]) and protein carbonyl. Furthermore, glutathione levels, catalase, superoxide dismutase, glutathione transferase and glutathione peroxidase activities were significantly decreased. A smear without ladder formation on agarose gel was also shown, indicating random DNA degradation. Pretreatment of rats with vanillin (150 mg/kg/day, i.p.), for 3 consecutive days before CCl(4) injection, protected kidney against the increase of MDA and degradation of membrane proteins compared to CCl(4)-treated rats and exhibited marked prevention against CCl(4)-induced nephropathology, oxidative stress and DNA damage. Kidney histological sections showed glomerular hypertrophy and tubular dilatation in CCl(4)-treated rats, however, in vanillin pretreated rats, these histopathological changes were less important and present a similar structure to that of control rats. These data indicated the protective role of vanillin against CCl(4)-induced nephrotoxicity and suggested its significant contribution of these beneficial effects.     

Antioxidant potential of Cymbopogon citratus extract: alleviation of carbon tetrachloride-induced hepatic oxidative stress and toxicity

This study was aimed to evaluate the effect of Cymbopogon citratus against carbon tetrachloride (CCl(4))-mediated hepatic oxidative damage in rats. Rats were administrated with C. citratus extract (100, 200 and 300 mg/kg b.w.) for 14 days before the challenge of CCl(4) (1.2 ml/kg b.w. p.o) on 13th and 14th days. Hepatic damage was evaluated by employing serum biochemical parameters (alanine aminotransferase-ALT, aspartate aminotransferase-AST and lactate dehydrogenase-LDH), malondialdehye (MDA) level, reduced GSH and antioxidant enzymes (catalase: CAT, glutathione peroxidase: GPX, quinone reductase: QR, glutathione S-transferase: GST, glutathione reductase: GR, glucose-6-phosphate dehyrogenase: G6PD). In addition, CCl(4)-mediated hepatic damage was further evaluated by histopathological examination. However, most of these changes were alleviated by prophylactic treatment of animals with C. citratus dose dependently (p < 0.05). The protection was further evident through decreased histopathological alterations in liver. The results of the present study indicated that the hepatoprotective effect of C. citratus might be ascribable to its antioxidant and free radical scavenging property.     

Effect of nonsteroidal anti-inflammatory drugs and the procarcinogen 1,2-dimethylhydrazine on the antioxidant defense system

The present study was designed to evaluate the effects of three nonsteroidal anti-inflammatory drugs (NSAIDs) with varying cycloxygenase selectivities on the small intestinal antioxidant enzyme status and surface characteristics during 1,2-dimethylhydrazine (DMH) administration. Male Sprague-Dawley rats were divided into five different groups: Group 1 (control, vehicle treated); group 2 (DMH treated, 30 mg/kg body weight/week, subcutaneously); group 3 (DMH + aspirin 60 mg/kg body weight); group 4 (DMH + celecoxib 6 mg/kg body weight); group 5 (DMH + etoricoxib 0.64 mg/kg body weight). Postmitochondrial fraction were isolated from the intestinal segments and different oxidative parameters and other parameters studied, such as the lipid peroxides, reduced and total glutathione, superoxide dismutase, catalase, glutathione reductase, glutathione S-transferase, nitric oxide, citrulline, and nucleic acids. At the end of 6 weeks of treatment, the results indicated a significant alteration in the antioxidative defense status of the intestine in the presence of the procarcinogen DMH, which was restored with the administration of NSAIDs. The study, therefore, suggests a possible mechanism for the chemopreventive effects of NSAIDs against the experimental intestinal cancer in rats.     

Protective role of melatonin against the mercury induced oxidative stress in the rat thyroid

Present study investigated the protective role of melatonin (MLT, 5 mg/kg body wt., ip) against the long term effects of mercuric chloride (MC; 2 and 4 mg/kg body wt., po) in the thyroid gland of the rats through certain antioxidative indices like superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione (GSH), catalase (CAT) and lipid peroxidation (LPO), other biochemical parameters such as succinate dehydrogenase (SDH), adenosine triphosphatase (ATPase), acid phosphatase (ACPase) and alkaline phosphatase (ALPase) were also measured. Antioxidative enzymes and other parameters showed a significant reduction while LPO and mercury levels increased significantly in a dose dependent manner in MC treated animals as compared to control groups. Co-treatment with MLT revealed no significant effect on antioxidative and metabolic indices in the thyroid gland of rats. The results of present study thus strongly suggest that mercury affected antioxidant defense system and other metabolic enzymes of thyroid. Co-administration of melatonin exerted a protective effect against mercury induced endocrine toxicity.     

Carbon tetrachloride-induced changes in the activity of phase II drug-metabolizing enzyme in the liver of male rats: role of antioxidants

Glutathione S-transferases and glutathione play an important role in the detoxification of most toxic agents. In the present study, the protective effects of some antioxidants (L-ascorbic acid (AA), vitamin E (VE) or garlic) on carbon tetrachloride-induced changes in the activity of alanine amino transferase (ALT), aspartate amino transferase (AST), glutathione S-transferase (GST), and the level of glutathione (GSH) and thiobarbituric acid reactive substances (TBARS) were studied. The activities of ALT, and AST were assayed in plasma, whereas the activity of GST and the levels of GSH and TBARS were determined in the livers of rats. The current study included two experiments. In the first experiment, animals received single oral dose of CCl4 (400 mg/kg body weight) after administration of AA (100 mg/kg b.w.), VE (100 mg/kg b.w.) or garlic (800 mg/kg b.w.) as single oral doses. In the second experiment, rats received repeated oral doses of antioxidants for 12 consecutive days followed by a single oral dose of CCl4 on the 13th day and killed after that by 24 h. Treatment of male rats with CCl4 significantly increased the activity of ALT and AST in plasma, and the levels of both GSH and TBARS in the liver. On the other hand, CCl4 inhibited the activity of GST after single dose treatment. Single-dose treatments of rats with AA, VE or garlic prior to the administration of CCl4 could not restore the alterations in the activity of ALT and AST caused by CCl4 to the normal control level. However, repeated dose treatments with these agents restored such alterations to the normal level. We observed that VE is more effective than AA and garlic in restoring the inhibition of GST activity caused by CCl4 to the normal level after single dose treatments. On the other hand, AA and VE are more effective than garlic in restoring the induced TBARS level caused by CCl4 to the normal control level after repeated dose treatments. It has been observed that the tested antioxidants were able to antagonize the toxic effects of CCl4, and such counteracting effects were more pronounced when they were administered as repeated doses prior to administration of CCl4.     

Anti-oxidant activities of<Emphasis Type="Italic">acanthopanax senticosus</Emphasis> stems and their lignan components

The antioxidant activities of Acanthopanax senticosus stems were evaluated in CCl4-intoxicated rats. The n-butanol fraction from the water extract of the stems, when pretreated orally at 200 mg/kg/day for 7 consecutive days in rats, was demonstrated to exhibit significant increases in antioxidant enzyme activities such as hepatic cytosolic superoxide dismutase, catalase and glutathione peroxidase by 30.31, 19.82 and 155%, respectively. The n-butanol fraction whereas showed a significant inhibition of serum GPT activity (65.79% inhibition) elevated with hepatic damage induced by CCl4-intoxication. Eleutheroside B, a lignan component, isolated from the n-butanol fraction was found to cause a moderate free radical scavenging effect on DPPH, its scavenging potency as indicated in IC50 value, being 58.5 microM. These results suggested that the stems of A. senticosus possess not only antioxidant but also hepatoprotective activities.