Antioxidant effect of 2-hydroxy-4-methoxy benzoic acid on ethanol-induced hepatotoxicity in rats

Alcoholic liver disease (ALD) is one of the most common diseases in society. A large number of studies are in progress to identify natural substances that are effective in reducing the severity of ALD. 2-Hydroxy-4-methoxy benzoic acid (HMBA), the active principle of Hemidesmus indicus, an indigenous Ayurvedic medicinal plant in India, is expected to significantly inhibit the development of liver injury in ethanol administration. It is expected to reduce the severity of liver damage in terms of body weight, hepatic marker enzymes, oxidative stress, antioxidant status and histological changes in ethanol-induced hepatotoxic rats. Hepatotoxicity was induced by administering 20% ethanol (5 g kg(-1) daily) for 60 days to male Wistar rats, which resulted in significantly decreased body weight and an increase in liver-body weight ratio. The liver marker enzymes aspartate transaminase, alanine transaminase, alkaline phosphatase, gamma-glutamyl transpeptidase and lactate dehydrogenase were elevated. In addition, the levels of plasma, erythrocyte and hepatic thiobarbituric acid reactive substances, hydroperoxides and conjugated dienes were also elevated in ethanol-fed rats as compared with those of the experimental control rats. Decreased activity of superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione, vitamin C and alpha-tocopherol was also observed on alcohol administration as compared with experimental control rats. HMBA was co-administered at a dose of 200 mug kg(-1) daily for the last 30 days of the experiment to rats with alcohol-induced liver injury, which significantly increased body weight, significantly decreased the liver-body weight ratio, transaminases, alkaline phosphatase, gamma-glutamyl transpeptidase and lactate dehydrogenase, significantly decreased the levels of lipid peroxidative markers, significantly elevated the activity of enzymic and non-enzymic antioxidants in plasma, erythrocytes and liver and also increased levels of plasma and liver vitamin C and alpha-tocopherol at the end of the experimental period as compared with untreated ethanol-administered rats. The histological changes were also in correlation with the biochemical findings. The results suggest that HMBA administration may afford protection against ethanol-induced liver injury in rats.     

Enhancement of antioxidant defense system by epigallocatechin-3-gallate during bleomycin induced experimental pulmonary fibrosis

Oxidative stress resulting from an imbalance between radical-generating and radical scavenging systems plays an important role in the pathogenesis of pulmonary fibrosis. Epigallocatechin-3-gallate (EGCG), a polyphenol and a major component of green tea, possess a potent antioxidant property. This study was designed to evaluate the potential antioxidative activity of EGCG in the plasma and lungs during bleomycin induced experimental pulmonary fibrosis. Intratracheal administration of bleomycin (6.5 U/kg body weight) to rats resulted in significant reduction of body weight, enzymic antioxidants (superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase) and non-enzymic antioxidants (reduced glutathione, vitamin C, vitamin E and vitamin A). Elevations in lung W/D (wet weight/dry weight) ratio, hydroxyproline content was observed with a synchronized increase in lipid peroxidation markers (thiobarbituric acid reactive substances and hydroperoxides). Intraperitoneal administration of EGCG at a dose of 20 mg/kg body weight significantly improved the body weight, enzymic and non enzymic antioxidants and considerably decreased the W/D ratio, hydroxyproline and lipid peroxidation marker levels. Histological observations also correlated with the biochemical parameters. Thus, this study confirms the beneficial use of EGCG in alleviating the oxidative stress induced during pulmonary fibrosis.     

N-acetylcysteine attenuates dimethylnitrosamine induced oxidative stress in rats

Oxidative stress has been implicated in the pathogenesis and progression of various hepatic disorders and hence screening for a good hepatoprotective and antioxidant agent is the need of the hour. The present study was aimed to investigate the hepatoprotective and antioxidant property of N-acetylcysteine (NAC) against dimethylnitrosamine (DMN) induced oxidative stress and hepatocellular damage in male Wistar albino rats. Administration of single dose of DMN (5 mg/kg b.w.; i.p.) resulted in significant elevation in the levels of serum aspartate transaminase and alanine transaminase, indicating hepatocellular damage. Oxidative stress induced by DMN treatment was confirmed by an elevation in the status of lipid peroxidation (LPO) and reduction in the activities of enzymic antioxidants such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase and in the levels of non-enzymic antioxidants, reduced glutathione, vitamin-C and vitamin-E in the liver tissue. DMN induced oxidative stress and hepatocellular membrane instability was further substantiated by a decline in the status of the membrane bound ATPases in the liver tissue. Post-treatment with NAC (50 mg/kg b.w.; p.o.) for 7 days effectively protected against the DMN induced insult to liver by preventing the elevation in the status of the serum marker enzymes and LPO, and restoring the activities of both the enzymic and non-enzymic antioxidants and membrane bound ATPases towards normalcy. These results demonstrate that NAC acts as a good hepatoprotective and antioxidant agent in attenuating DMN induced oxidative stress and hepatocellular damage.     

Glycine modulates hepatic lipid accumulation in alcohol-induced liver injury

We studied the effect of administering glycine, a non-essential amino acid, on serum and tissue lipids in experimental hepatotoxic Wistar rats. All the rats were fed standard pellet diet. Hepatotoxicity was induced by administering ethanol (7.9 g kg(-1)) for 30 days by intragastric intubation. Control rats were given isocaloric glucose solution. Glycine was subsequently administered at a dose of 0.6 g kg(-1) every day by intragastric intubation for the next 30 days. Average body weight gain at the end of the total experimental period of 60 days was significantly lower in rats supplemented with alcohol, but improved on glycine treatment. Feeding alcohol significantly elevated the levels of cholesterol, phospholipids, free fatty acids and triglycerides in the serum, liver and brain as compared with those of the control rats. Subsequent glycine supplementation to alcohol-fed rats significantly lowered the serum and tissue lipid levels to near those of the control rats. Microscopic examination of alcohol-treated rat liver showed inflammatory cell infiltrates and fatty changes, which were alleviated on treatment with glycine. Alcohol-treated rat brain demonstrated edema, which was significantly lowered on treatment with glycine. In conclusion, this study shows that oral administration of glycine to alcohol-supplemented rats markedly reduced the accumulation of cholesterol, phospholipids, free fatty acids and triglycerides in the circulation, liver and brain, which was associated with a reversal of steatosis in the liver and edema in the brain.     

Role of leptin on alcohol-induced oxidative stress in Swiss mice.

Previous studies suggest a possible link between leptin and hepatic inflammation; however, the role of leptin on liver disease remains unclear. The purpose of the present study was to evaluate the effect of leptin on tissue lipid peroxidation and the antioxidant status in experimental hepatotoxicity. Administering ethanol (6.32 g/kg body weight) to 4-week-old healthy mice for 45 days resulted in significantly elevated levels of tissue thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD) and lowered activities of superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and glutathione related enzymes such as glutathione peroxidase (GPx) and glutathione S-transferase (GST) as compared with those of the control mice. subsequent to the experimental induction of hepatotoxicity (i.e. after the initial period of 30 days) exogenous leptin was simultaneously administered (230 microg/kg body weight) every alternate day for 15 days along with the daily dose of alcohol. Leptin administration to control and alcohol-treated mice significantly reduced the weight gain, significantly elevated the liver and kidney levels of TBARS and CD, and significantly lowered the levels of enzymic and non-enzymic antioxidants as compared with the untreated control and alcohol supplemented mice. It is postulated that the increase in systemic leptin levels enhance the oxidative stress, and lower the antioxidant defence, leading to augmented hepatic inflammation in alcoholic liver disease.     

Silymarin modulates the oxidant-antioxidant imbalance during diethylnitrosamine induced oxidative stress in rats

Oxidative stress is a common mechanism contributing to initiation and progression of hepatic damage in a variety of liver disorders. Hence, there is a great demand for the development of agents with potent antioxidant effect. The aim of the present investigation is to evaluate the efficacy of silymarin as a hepatoprotective and an antioxidant against diethylnitrosamine induced hepatocellular damage. Single intraperitoneal administration of diethylnitrosamine (200 mg/kg) to rats resulted in significantly elevated levels of serum aspartate transaminase (AST) and alanine transaminase (ALT), which is indicative of hepatocellular damage. Diethylnitrosamine induced oxidative stress was confirmed by elevated levels of lipid peroxidation and decreased levels of superoxide dismutase (SOD), catalase, glutathione peroxidase, glutathione reductase (GR) and glutathione-S-transferase (GST) in the liver tissue. The status of non-enzymic antioxidants like, vitamin-C, vitamin-E and reduced glutathione (GSH) were also found to be decreased in diethylnitrosamine administered rats. Further, the status of membrane bound ATPases was also altered indicating hepatocellular membrane damage. Posttreatment with the silymarin (50 mg/kg) orally for 30 days significantly reversed the diethylnitrosamine induced alterations in the liver tissue and offered almost complete protection. The results from the present study indicate that silymarin exhibits good hepatoprotective and antioxidant potential against diethylnitrosamine induced hepatocellular damage in rats.     

Hepatoprotective effect of chrysin on prooxidant‐antioxidant status during ethanol‐induced toxicity in female albino rats

Objectives To evaluate the effect of chrysin, a natural, biologically active compound extracted from many plants, honey and propolis, on the tissue and circulatory antioxidant status, and lipid peroxidation in ethanol‐induced hepatotoxicity in rats. Methods Rats were divided into four groups. Groups 1 and 2 received isocaloric glucose. Groups 3 and 4 received 20% ethanol, equivalent to 5 g/kg bodyweight every day. Groups 2 and 4 received chrysin (20 mg/kg bodyweight) dissolved in 0.5% dimethylsulfoxide. Key findings The results showed significantly elevated levels of tissue and circulatory thiobarbituric acid reactive substances, conjugated dienes and lipid hydroperoxides, and significantly lowered enzymic and non‐enzymic antioxidant activity of superoxide dismutase, catalase and glutathione‐related enzymes such as glutathione peroxidase, glutathione reductase, glutathione‐S‐transferase, reduced glutathione, vitamin C and vitamin E in ethanol‐treated rats compared with the control. Chrysin administration to rats with ethanol‐induced liver injury significantly decreased the levels of thiobarbituric acid reactive substances, lipid hydroperoxides and conjugated dienes, and significantly elevated the activity of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione‐S‐transferase and the levels of reduced glutathione, vitamin C and vitamin E in the tissues and circulation compared with those of the unsupplemented ethanol‐treated rats. The histological changes observed in the liver and kidney correlated with the biochemical findings. Conclusions Chrysin offers protection against free radical‐mediated oxidative stress in rats with ethanol‐induced liver injury.     

Effect of grape (Vitis vinifera L.) leaf extract on alcohol induced oxidative stress in rats

Alcoholic liver disease is a major medical complication of drinking alcohol. Oxidative stress plays an important role in the development of alcohol liver disease. The present study was carried to evaluate the effect of grape leaf extract (GLEt) on antioxidant and lipid peroxidation states in liver and kidney alcohol induced toxicity. In vitro studies with DPPH* and ABTS*(+) (cation radical) showed that GLEt possesses antioxidant activity. In vivo administration of ethanol (7.9 g/kg bw/day) for 45 days resulted an activity of liver marker enzymes (AST, ALT, ALP and GGT), lipid peroxidation markers (TBARS, lipid hydroperoxides) in liver and kidney with significantly lower activity of SOD, CAT, GPx, GST and non-enzymatic antioxidants (vitamin E, vitamin C and GSH) in liver and kidney as compared with control rats. Administration of ethanol along with GLEt significantly decreased the activities of liver markers enzyme in serum towards near normal level. GLEt at a dose of 100 mg/kg was highly effective than 25 and 50 mg/kg body weight. In addition GLEt also significantly reduced the levels of lipid peroxidation and addition, significantly restored the enzymic and non-enzymatic antioxidants level in liver and kidney of alcohol administration rats. This observation was supplemented by histopathological examination in liver and kidney. Our data suggest that GLEt exerts its protective effect by decreased the lipid peroxidation and improving antioxidants status, thus proving itself as an effective antioxidant in alcohol induced oxidative damage in rats.     

Short-term dietary restriction modulates liver lipid peroxidation in carbon tetrachloride-intoxicated rats

We investigated whether dietary restriction (DR) can protect the liver against the acute toxicity of carbon tetrachloride (CCl4). Adult female Wistar rats received a quantum of diet representing 75 and 50 percent of the food intake of control rats fed ad libitum (25% and 50% daily regimen, respectively) for 30 days. A single dose of CCl4 (3 mL kg(-1) b.w.) was administered subcutaneously at the end of the feeding period. Lipid peroxidation, as thiobarbituric acid reactive substance, conjugated dienes, lipid hydroperoxides and the hepatic markers alanine transaminase, aspartic transaminase, and alkaline phosphatase were significantly decreased in food-restricted rats. The enzymic antioxidants superoxide dismutase, catalase, glutathione peroxidase and the non-enzymic antioxidant glutathione were significantly increased in both groups. The magnitude of liver damage after CCl4 treatment was lower in food-restricted animals than in ad libitum-fed animals. The results suggest that dietary restriction increases the resistance of the liver and protects against oxidative insult produced by an acute dose of CCl4.     

Induction of oxidative stress in rat brain by acrylonitrile (ACN).

Chronic treatment with acrylonitrile (ACN) has been shown to produce a dose-related increase in glial cell tumors (astrocytomas) in rats. The mechanism(s) for ACN-induced carcinogenicity remains unclear. While ACN has been reported to induce DNA damage in a number of short-term systems, evidence for a genotoxic mechanism of tumor induction is the brain is not strong. Other toxic mechanisms appear to participate in the induction of tumor or induce the astrocytomas solely. In particular, nongenotoxic mechanisms of carcinogen induction have been implicated in this ACN-induced carcinogenic effect in the rat brain. One major pathway of ACN metabolism is through glutathione (GSH) conjugation. Extensive utilization and depletion of GSH, an important intracellular antioxidant, by ACN may lead to cellular oxidative stress. The present study examined the ability of ACN to induce oxidative stress in male Sprague-Dawley rats. Rats were administered ACN at concentrations of 0, 5, 10, 100, or 200 ppm in the drinking water and sampled after 14, 28, or 90 days of continuous treatment. Oxidative DNA damage indicated by the presence of 8-hydroxy-2'-deoxyguanosine (OH8dG) and lipid peroxidation indicated by the presence of malondialdehyde (MDA), a lipid peroxidation product, in rat brains and livers were examined. The levels of reactive oxygen species (ROS) were also determined in different rat tissues. Both the levels of nonenzymatic antioxidants (GSH, vitamin E) and the activities of enzymatic antioxidants (catalase, superoxide dismutase, glutathione peroxidase) in rat brains and livers were measured. Increased levels of OH8dG, MDA, and ROS were found in the brains of ACN-treated rats. Decreased levels of GSH and activities of catalase and SOD were also observed in the brains of ACN-treated rats compared to the control group. Interestingly, there were no changes of these indicators of oxidative stress in the livers of ACN-treated rats. Rat liver is not a target for ACN-induced carcinogenesis. These data indicate that ACN selectively induces oxidative stress in rat brain at doses that produce carcinogenesis in chronic treatment studies.     

Ciprofloxacin-induced glutathione redox status alterations in rat tissues

The possible oxidative stress inducing effect of a fluoroquinolone (FQ) antibiotic, ciprofloxacin (CPFX), was investigated in rats measuring glutathione redox status. For this purpose, the drug was administered to rats as two different single doses (100 and 150 mg/kg, ip) or a repeated dose (500 mg/kg/d, ig, for 5d). Then, total and oxidized glutathione levels were determined in hepatic and cerebral tissues of the rats by an enzymatic cycling assay, and the glutathione redox status was calculated. The possible protective effects of vitamin E or allopurinol against CPFX-induced alterations on glutathione system have also been examined. Following both routes of administration of CPFX, the total glutathione content of the liver, but not of brain decreased significantly. The oxidized glutathione (GSSG) in the brain increased after single or repeated dose treatments, but only with repeated doses of CPFX in the liver. CPFX induced dose-dependent alterations in the glutathione redox status in both tissues. With single doses the effect was more pronounced in cerebral tissue, and with repeated ig doses it was significant in both tissues. Pretreatment of rats with vitamin E or allopurinol before the administration of CPFX provided marked protection against glutathione redox status alterations in both tissues. Our results, thus, indicate that CPFX treatment introduces an oxidative stress in cerebral and hepatic tissues of rat.     

Ciprofloxacin‐Induced Glutathione Redox Status Alterations in Rat Tissues

The possible oxidative stress inducing effect of a fluoroquinolone (FQ) antibiotic, ciprofloxacin (CPFX), was investigated in rats measuring glutathione redox status. For this purpose, the drug was administered to rats as two different single doses (100 and 150 mg/kg, ip) or a repeated dose (500 mg/kg/d, ig, for 5d). Then, total and oxidized glutathione levels were determined in hepatic and cerebral tissues of the rats by an enzymatic cycling assay, and the glutathione redox status was calculated. The possible protective effects of vitamin E or allopurinol against CPFX‐induced alterations on glutathione system have also been examined. Following both routes of administration of CPFX, the total glutathione content of the liver, but not of brain decreased significantly. The oxidized glutathione (GSSG) in the brain increased after single or repeated dose treatments, but only with repeated doses of CPFX in the liver. CPFX induced dose‐dependent alterations in the glutathione redox status in both tissues. With single doses the effect was more pronounced in cerebral tissue, and with repeated ig doses it was significant in both tissues. Pretreatment of rats with vitamin E or allopurinol before the administration of CPFX provided marked protection against glutathione redox status alterations in both tissues. Our results, thus, indicate that CPFX treatment introduces an oxidative stress in cerebral and hepatic tissues of rat.     

Monosodium glutamate-induced oxidative damage and genotoxicity in the rat: modulatory role of vitamin C, vitamin E and quercetin

Monosodium glutamate (MSG) continues to function as a flavor enhancer in West African and Asian diets. The present study examines the modulatory effects of dietary antioxidant vitamin C (VIT C), vitamin E (VIT E) and quercetin on MSG-induced oxidative damage in the liver, kidney and brain of rats. In addition, the effect of these antioxidants on the possible genotoxicity of MSG was investigated in a rat bone marrow micronuclei model. MSG administered intraperitoneally at a dose of 4 mg/g body wt markedly increase malondialdehyde (MDA) formation in the liver, the kidney and brain of rats. Simultaneous administration of VIT C, VIT E and quercetin to MSG-treated rats significantly reduced this increase in MDA induced by MSG. VIT E reduced lipid peroxidation most in the liver followed by VIT C and then quercetin, while VIT C and quercetin showed a greater ability to protect the brain from membrane damage than VIT E. The decreased glutathione (GSH) level elicited by MSG in the three organs corresponded with marked increase in the activity of glutathione-S-transferase (GST). While MSG increased (P < 0.001) the activities of superoxide dismutase and catalase in the liver, it decreased significantly the activities of these enzymes in the kidney and the brain. The three antioxidants were effective at ameliorating the effects of MSG on GSH levels and the enzymes in the three organs examined. While MSG increased the activity of glucose-6-phosphatase in the liver and kidneys of rats (P < 0.001), the activity of the enzyme was abysmally low in the brain. There were marked increases in the activities of alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl transferase in rats treated with MSG. The antioxidants tested protected against MSG-induced liver toxicity significantly. MSG at a dose of 4 mg/g significantly (P < 0.01) induced the formation of micronucleated polychromatic erythrocytes (MNPCEs). Co-treatment of rats with VIT C and quercetin inhibited the induction of MNPCEs by MSG (P < 0.001). VIT E failed to protect against MSG-induced genotoxicity. The results indicate that dietary antioxidants have protective potential against oxidative stress induced by MSG and, in addition, suggest that active oxygen species may play an important role in its genotoxicity.     

Inhibition of diquat-induced lipid peroxidation and toxicity in precision-cut rat liver slices by novel antioxidants

The ability of the novel antioxidants U-74,006F and U-78,517G and a known antioxidant (N,N'-diphenyl-p-phenylenediamine, (DPPD)) to inhibit chemically induced (diquat dibromide) oxidative stress was examined in precision-cut liver slices. Previous studies in rat liver microsomes demonstrated the ability of these antioxidants to inhibit lipid peroxidation without preventing redox cycling of diquat. Diquat (1 mM) initiated lipid peroxidation in liver slices prepared from F344 rats. A 30-min preincubation with antioxidants inhibited formation of thiobarbituric acid reactive substances to control levels; ethane evolution, when elevated, was also inhibited by antioxidants. The toxicity of diquat (100 microM-3 mM) was evaluated in liver slices; 1 and 3 mM diquat caused decreases in intracellular K+ and intracellular LDH. Preincubation with antioxidants substantially decreased the toxicity of diquat as indicated by K+ and LDH. Diquat significantly decreased total glutathione levels in the slices; the antioxidants did not significantly inhibit this diquat-dependent effect. In summary, diquat, a compound which undergoes redox cycling and produces oxidative stress, was shown to produce lipid peroxidation, glutathione depletion, and toxicity in liver slices. Two experimental antioxidants, a 21-aminosteroid (U-74,006F) and a trolox-amine (U-78,517G) as well as a known antioxidant (DPPD) were shown to be effective in preventing lipid peroxidation and reducing the subsequent toxicity.     

Tetrahydrocurcumin: effect on chloroquine-mediated oxidative damage in rat kidney

Tetrahydrocurcumin is an antioxidative substance, which is derived from curcumin, the component of turmeric. In the present investigation, the effect of tetrahydrocurcumin and curcumin against chloroquine-induced nephrotoxicity were studied in female wistar rats. Oral administration of tetrahydrocurcumin significantly prevented the occurrence of chloroquine (970 mg/kg body weight)-induced renal damage. Upon administration of tetrahydrocurcumin to chloroquine-treated rats, the level of lipid peroxidation was significantly decreased while the levels of non-enzymic and enzymic antioxidants were significantly increased in kidney. Oral administration (80 mg/kg body weight) attenuated the chloroquine-induced nephrotoxicity by significantly decreased levels of serum urea and creatinine with significant normalization of creatinine clearance. On administration of tetrahydrocurcumin, the depleted renal antioxidant defense system (enzymatic and non-enzymatic antioxidants) was significantly increased in rats treated with chloroquine. These biochemical observations were supplemented by histopathological examination of kidney section. These results suggest that administration of chloroquine imposes an oxidative stress to renal tissue and that tetrahydrocurcumin protects the oxidative damage associated with chloroquine.     

Chemoprotective effect of lipoic acid against cyclophosphamide-induced changes in the rat sperm

Treatment with cyclophosphamide (CP), a commonly used anticancer and immunosuppressive agent, may result in oligospermia and azoospermia. CP administration induces oxidative stress and is cytotoxic to normal cells. In this context, we have studied the effect of an established antioxidant, lipoic acid on its influence on CP-induced oxidative injury in rat sperm. In this study, we have assessed the possible protective efficacy of lipoic acid on the sperm characteristics, peroxidative damages and abnormal antioxidant levels in the epididymal sperm of CP-administered rats. Male Wistar rats of 140+/-20 g were categorized into four groups. Two groups of rats were administered CP (15 mg/kg body weight once a week for 10 weeks by oral gavage) to induce testicular toxicity; one of these groups received lipoic acid treatment (35 mg/kg body weight intraperitoneally once a week for 10 weeks; 24 h prior to CP administration). A vehicle treated control group and a lipoic acid drug control group were also included. CP-treated rats showed a significant decrease in sperm count and motility with an increase in dead and abnormal sperms. The epididymal sperm of untreated CP-exposed rats showed 1.9-fold increase in lipid peroxidation, along with a significant increase in protein carbonyl level. These changes were associated with significant increase in DNA damage in the sperm as evidenced by increased single strand breaks in fluorimetric analysis of DNA unwinding (FADU). In rats treated with CP, abnormal changes in the activities/levels of enzymic (superoxide dismutase, catalase and glutathione peroxidase) and non-enzymic (reduced glutathione, ascorbate and alpha-tocopherol) antioxidants, were also observed. Pretreatment with lipoic acid improved the semen quality and reduced the oxidative stress and DNA damage induced by CP, thereby demonstrating the protection rendered by lipoic acid.     

Oxidative stress in rats after 60 days of hypergalactosemia or hyperglycemia

Two of the models used in current diabetes research include the hypergalactosemic rat and the hyperglucosemic, streptozotocin-induced diabetic rat. Few studies, however, have examined the concurrence of these two models regarding the effects of elevated hexoses on biomarkers of oxidative stress. This study compared the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase and the concentrations of glutathione, glutathione disulfide, and thiobarbituric acid reactants (as a measure of lipid peroxidation) in liver, kidney, and heart of Sprague-Dawley rats after 60 days of either a 50% galactose diet or insulin deficiency caused by streptozotocin injection. Most rats from both models developed bilateral cataracts. Blood glucose and glycosylated hemoglobin A(1c) concentrations were elevated in streptozotocin diabetic rats. Streptozotocin diabetic rats exhibited elevated activities of renal superoxide dismutase, cardiac catalase, and renal and cardiac glutathione peroxidase, as well as elevated hepatic lipid peroxidation. Insulin treatment of streptozotocin-induced diabetic rats normalized altered markers. In galactosemic rats, hepatic lipid peroxidation was increased whereas glutathione reductase activity was diminished. Glutathione levels in liver were decreased in diabetic rats but elevated in the galactosemic rats, whereas hepatic glutathione disulfide concentrations were decreased much more in diabetes than in galactosemia. Insulin treatment reversed/prevented all changes caused by streptozotocin-induced diabetes. Lack of concomitance in these data indicate that the 60-day galactose-fed rat is not experiencing the same oxidative stress as the streptozotocin diabetic rat, and that investigators must be cautious drawing conclusions regarding the concurrence of the effects of the two animal models on oxidative stress biomarkers.     

Antihyperglycaemic and antioxidant effect of rutin, a polyphenolic flavonoid, in streptozotocin-induced diabetic wistar rats

Flavonoids are non-nutritive dietary components that are widely distributed in plants. The present study investigated the antihyperglycaemic and antioxidant effect of rutin, a polyphenolic flavonoid in normal and streptozotocin-induced diabetic Wistar rats. Diabetes as induced in rats by an intraperitoneal injection of streptozotocin. Rutin was orally administered to normal and diabetic rats for a period of 45 days. Fasting plasma glucose, glycosylated haemoglobin, thiobarbituric acid reactive substances and lipid hydroperoxides were significantly (P<0.05) increased, whereas insulin, C-peptide, total haemoglobin, protein levels, non-enzymic antioxidants (glutathione, vitamin C, vitamin E and ceruloplasmin) were decreased significantly (P<0.05) in diabetic rats. Oral administration of rutin to diabetic rats significantly (P<0.05) decreased fasting plasma glucose, glycosylated haemoglobin and increased insulin, C-peptide, haemoglobin and protein levels. Administration of rutin also decreased thiobarbituric acid reactive substances and lipid hydroperoxides and increased the non-enzymic antioxidants significantly (P<0.05). Treatment of normal rats with rutin did not significantly (P<0.05) alter any of the parameters studied. These results show that rutin exhibits antihyperglycaemic and antioxidant activity in streptozotocin-induced diabetic rats.     

Caspase-3 and heat shock protein-70 in rat liver treated with aflatoxin B1: effect of melatonin.

In the present study, caspase-3 enzyme activity (apoptotic marker) and heat shock protein-70 (HSP70) expression in male rat liver after aflatoxin B1 (AFB1) treatment and the effect of melatonin (MEL) were investigated. Four groups of 20 rats each were used: controls, MEL-treated rats (MEL dose, 5 mg/kg body wt), AFB1-treated rats (50 microg/kg body wt) and MEL+AFB1-treated rats. After 8 weeks of daily treatment, biochemical assays in liver homogenates were done. The caspase-3 enzyme activity was measured using colorimetric method while the level of HSP70 expression was determined using dot blot analysis. In addition, the tissue levels of lipid peroxides (LPO), nitric oxide (NO), glutathione (GSH) and the enzyme activities of glutathione reductase (GR) and glutathione peroxidase (GSPx) were determined using colorimetric methods. The levels of caspase-3 activities and HSP70 level in AFB1 group were significantly higher than control group. Concomitantly, the levels of oxidative stress indices, LPO and NO, were significantly increased while the levels of antioxidants, GSH, GSPx and GR in AFB1 group were significantly decreased compared to their levels in controls. Caspase-3 activity was positively correlated with LPO while negatively correlated with GSH in rat livers treated with AFB1. The levels of caspase-3 activity, LPO, NO and HSP70 expression were significantly lower while the levels of GSH, GSPx and GR activities were significantly higher in MEL+AFB1 group than AFB1 group. In conclusion, higher levels of caspase-3 activity and HSP70 expression were associated with oxidative stress in rat liver treated with AFB1. The increased HSP70 expression in liver of AFB1 group may be due to a compensatory defense mechanism. MEL may effectively normalize the impaired antioxidants status, which consequently reduce both expression of HSP70 and apoptotic dysregulation in the liver. Thus, clinical application of MEL as therapy may benefit in cases of aflatoxicosis.