Influence of amodiaquine treatment on microsomal lipid peroxidation and antioxidant defense systems of rats

The effects of single and multiple doses amodiaquine treatment on enzymatic and non-enzymatic antioxidant profiles and hepatic microsomal lipid peroxidation were investigated in rats. Treatment of rats with 10 mg/kg (single dose) amodiaquine resulted in 10% and 63% increases, respectively in the activities of liver superoxide dismutase and glutathione peroxidase (P<0.01), while the activity of liver catalase was significantly reduced by 26% compared to control. The levels of serum vitamins A, C and beta-carotene were lowered following amodiaquine treatment. Following multiple dose (10 mg/kg for 4 consecutive days) amodiaquine treatment, activities of superoxide dismutase and glutathione peroxidase were increased by 30% and 133% respectively while catalase activity was decreased by 45%. Similarly, serum vitamins A, C and beta-carotene levels were markedly decreased. In the single dose study, the levels of malondialdehyde and the activity of glutathione S-transferase were increased by 15% and 44% respectively while the reduced glutathione was decreased by 25% compared to control. Malondialdehyde level was highly increased (P<0.001) by 71% following multiple amodiaquine treatment. Reduced glutathione was decreased by 55% and unlike in the single dose study, activity of glutathione S-transferase was decreased by 60% compared to control. The activities of serum aspartate amino transferase, alanine amino transferase, ornithine carbamyl transferase and gamma-glutamyl transferase were significantly increased by both single and multiple doses of amodiaquine treatment (P<0.01). The alteration in enzymatic and non-enzymatic antioxidant defense system, increase in lipid peroxidation and increase in the activities of serum enzymes following amodiaquine treatment suggests damage to the liver and could subject the organ to further oxidative stress. The relevance of this to continuous exposure to amodiaquine therapy should be considered.     

Antioxidant Effect of Tinospora cordifolia Extract in Alloxan-induced Diabetic Rats

Many plants are claimed to possess antidiabetic and antioxidant activity. In practice, it is being increasingly recognized to be an alternative approach to modern medicine. This study assess the antioxidant capacity of Tinospora cordifolia stem methanol extract in daily oral administration of 500 mg/kg of body weight for 40 days in alloxan induced diabetic rats. The erythrocytes membrane lipid peroxide and catalase activity was increased where as the activities of superoxide dismutase, glutathione peroxidase were found to be decreased significantly (P<0.01) in alloxan-induced diabetic rats. The levels of lipid peroxide in liver of diabetic rats increased significantly (P<0.01) and catalase, superoxide dismutase, glutathione peroxidase in liver was significantly decreased in alloxan-induced diabetic rats, when compared to normal rats. After treatment of methanol Tinospora cordifolia stem extract brings back to normal (P<0.01) in the erythrocytes membrane and liver cell enzymes activities.     

Differential response of cellular antioxidant mechanism of liver and kidney to arsenic exposure and its relation to dietary protein deficiency

The effect on antioxidant defense system of liver and kidney of sub-acute i.p. exposure to sodium arsenite (3.33 mg/kg b.w. per day) for 14 days was studied in male Wistar rats fed on an adequate (18%) or a low (6%) protein diet. Following arsenic treatment, liver showed significantly enhanced concentration of glutathione and increased activities of glutathione reductase and glutathione-S-transferase on either of the dietary protein levels. Liver glutathione peroxidase and glucose-6-phosphate dehydrogenase activities increased significantly on an adequate protein diet while glutathione peroxidase activity decreased significantly on a low-protein diet. Lipid peroxidation and superoxide dismutase activity of liver remained unaltered on either of the dietary protein levels. On the other hand, kidney of arsenic-treated rats receiving either of the dietary protein levels showed significantly increased lipid peroxidation and decreased superoxide dismutase and catalase activities. Kidney glutathione content and glutathione reductase activity remained unaltered while glutathione peroxidase activity increased and glutathione-S-transferase activity decreased significantly on a low-protein diet following exposure to arsenic. On an adequate protein diet glucose-6-phosphate dehydrogenase activity in kidney, however, became significantly elevated following arsenic treatment. In Wistar rats, after 14 days of treatment with 3.33 mg As/kg b.w. i.p. the kidney seemed to be more sensitive to arsenic, and liver appears to be protected more by some of the antioxidant components, such as, glutathione, glutathione-S-transferase and glucose-6-phosphate dehydrogenase. It appears that low-protein diet influences the response of some of the cellular protective components against arsenic insult but does not lead to unique findings.     

The effects of paeoniflorin on LPS-induced liver inflammatory reactions

Paeoniflorin (PF), a monoterpene glucoside, is a primary bioactive component of paeony, the root extract of Paeonia lactiflora. We tested the antioxidant effects of PF and its ability to prevent lipopolysaccharide (LPS)-induced oxidative stress. We intraperitoneally administered PF (2.5, 5, or 10 mg/kg) to rats for 20 days. On day 21, we injected the rats with LPS 4 h before sacrifice and measured serum levels of glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, lactate dehydrogenase as well as the levels of malondialdehyde, superoxide dismutase, catalase, and glutathione peroxidase in liver whole-cell homogenates and mitochondrial fractions. LPS treatment increased levels of glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, lactate dehydrogenase, and malondialdehyde, but PF treatment blocked these increases. LPS treatment also decreased antioxidant levels of superoxide dismutase, catalase, and glutathione peroxidase, but PF blocked these decreases. PF also protected liver tissue, as shown by histopathology. These results suggest that PF can protect against LPS-induced liver inflammation.     

Taurine treatment reduces hepatic lipids and oxidative stress in chronically ethanol-treated rats

In this study, we evaluated whether taurine treatment has a protective effect on the prooxidant-antioxidant state following chronic ethanol treatment in rats. Rats were given water containing 20% ethanol (v/v) as drinking water for 3 months. Chronic ethanol treatment in drinking water resulted in increased oxidative stress in the liver of rats. Taurine treatment was performed by adding 1% taurine (w/v) to the drinking water plus injection (400 mg/kg body weight) intraperitoneally 3 times/week for 28 d after ethanol cessation in chronically ethanol-treatad rats. This treatment starting after ethanol cessation caused a significant decreases in serum transaminase activities and hepatic total lipid, triglyceride, malondialdehyde, and diene conjugate levels and significant increases in hepatic glutathione, vitamin E, and vitamin C levels, but did not alter the activities of superoxide dismutase, glutathione peroxidase, and glutathione transferase in the liver as compared with chronically ethanol-treated rats. Accordingly, we propose that taurine has a restorative effect on ethanol-induced hepatic damage by decreasing oxidative stress.     

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

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

Manipulation of mouse organ glutathione contents. II: Time and dose-dependent induction of the glutathione conjugation system by phenolic antioxidants

After 14 days of oral butylated hydroxyanisole (BHA) administration (1000 mg/kg/day) the tissue glutathione levels of male NMRI mice were increased by 74-141% in liver, lung, duodenum and intestine and after similar butylated hydroxytoluene (BHT) treatment by 18-85% in the liver, lung, spleen and the gastrointestinal tract. Doses of 100 mg/kg/day significantly elevated the glutathione content in the lung (BHA, BHT), duodenum (BHA) and intestine (BHA), while 10 mg/kg/day affected only lung glutathione content (BHA). BHA treatment (1000 mg/kg/day) induced GST activities significantly (138-1335%) in all organs investigated except the spleen, i.e. liver, lung, kidney and the entire gastrointestinal tract, while a similar dose of BHT increased GST activities in the liver, duodenum, intestine and colon by 26-339%. Daily doses of 100 mg/kg/day significantly induced GST activities only in the liver (BHA, BHT), lung (BHA) and kidney (BHA). Lower doses of BHA or BHT did not significantly affect GST activities in the organs investigated (except 10 mg BHA/kg/day in the lung). Comparison of the time course of induction of the glutathione conjugation system in various organs after different doses of antioxidants indicated no change between 5 and 14 days of treatment with all doses used (1-1000 mg/kg). Only the lung glutathione level showed a tendency to increase with low dose BHA by extending the time of treatment. The time course of the liver glutathione content between single doses of 100 mg/kg BHA or BHT revealed an initial decline followed by an increase above control values 2 days (BHA) or 5 days (BHT) after the first application. The glutathione levels of the lung and the duodenum increased without a preceding decline. Only the second dose of BHT caused a temporary decrease to control values of the elevated glutathione level in the duodenum. All animals (at any dose of BHA or BHT) showed control values of serum transaminase activities. These results suggest: The induction threshold of the glutathione conjugation system in various mouse organs is greater than or equal to 100 mg/kg for BHA and BHT. Chronic administration of these compounds did not change these results (except the lung glutathione level after low dose BHA). Elevated hepatic glutathione levels might be the result of an activated synthesis caused by a preceding loss of glutathione. Chronic BHA or BHT treatment did not cause hepatotoxic effects, as evaluated by serum transaminases, in male mice.     

Hippophae rhamnoides attenuates nicotine-induced oxidative stress in rat liver

The effects of vitamin E and Hippophae rhamnoides L. (Elaeagnaceae) extract (HRe-1) on nicotine-induced oxidative stress in rat liver were investigated. Four groups, eight rats each, were used in this study, and the supplementation period was 3 weeks. The groups were: nicotine (0.5?mg/kg/day, intraperitoneal (i.p.)); nicotine plus vitamin E (75?mg/kg/day, intragastric (i.g.)); nicotine plus HRe-1 (250?mg/kg/day, i.g.); and the control group. The malondialdehyde and nitric oxide levels, glutathione peroxidase, glutathione S-transferase, glutathione reductase, superoxide dismutase, and total and non-enzymatic superoxide scavenger activities were measured spectrophotometrically in supernatants of the tissue homogenates. Nicotine increased the malondialdehyde level in liver tissue compared with control. This nicotine-induced increase in lipid peroxidation was prevented by both vitamin E and HRe-1. Superoxide dismutase activity was higher in the nicotine plus vitamin E-supplemented group compared with nicotine and control groups. Glutathione reductase activity was higher in the nicotine group compared with the control group. However, glutathione peroxidase activity in the control group was higher than the levels in the nicotine, and the nicotine plus HRe-1 supplemented groups. The nitric oxide level was higher in the nicotine group compared with all other groups. Total and non-enzymatic superoxide scavenger activities and glutathione S-transferase activity were not affected by any of the treatments. Our results suggest that Hippophae rhamnoides extract as well as vitamin E can protect the liver against nicotine-induced oxidative stress.     

Bisphenol A induces reactive oxygen species generation in the liver of male rats

Bisphenol A, an environmental contaminant, widely used as a monomer in polycarbonate plastics, has been shown to cause abnormalities in liver of rats and mice. The nature and mechanism of action of bisphenol A on liver is not clear. The aim of the present study was to investigate if bisphenol A induces oxidative stress in the liver of rats and if co-administration of vitamin C, an antioxidant, can prevent oxidative stress. Bisphenol A (0.2, 2.0 and 20 micro g/kg body weight per day) and bisphenol A+vitamin C (0.2, 2.0, 20 micro g+40 mg/kg body weight per day) was orally administered to rats for 30 days. After 24 h of the last treatment, rats were killed using overdose of anesthetic ether. Body weights of the animals and the weights of liver showed no significant changes. The activities of antioxidant enzymes, superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase were decreased in mitochondrial and microsome-rich fractions of liver. The levels of hydrogen peroxide and lipid peroxidation increased in the treated rats when compared with the corresponding group of control animals. Activity of alanine transaminase, a marker enzyme of hepatic injury remained unchanged in the treated rats as compared with the corresponding control rats. Co-administration of bisphenol A and vitamin C showed no changes in the activities of superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase and in the levels of hydrogen peroxide and lipid peroxidation as compared with the corresponding control groups. The results indicated that bisphenol A induces oxidative stress in the liver of rats by decreasing the antioxidant enzymes. Co-administration of vitamin C reversed the effects of bisphenol A-induced oxidative stress in the liver of rats.     

Biochemical Changes Induced in Liver and Serum of Aflatoxin B1‐Treated Male Wistar Rats: Preventive Effect of Picroliv

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

Nitrofurantoin-Induced Hepatic and Pulmonary Biochemical Changes in Mice Fed Different Vitamin E Doses

Abstract: The hepatic and pulmonary effects of nitrofurantoin (40 mg/kg, intraperitoneally) were determined at 4 and 24 hr following its administration in mice fed for 10 weeks with a vitamin E sufficient, deficient or enriched diet. Liver glutathione (GSH) was reduced by nitrofurantoin at 4 hr but was unchanged 20 hr later. Nitrofurantoin did not affect liver glutathione peroxidase, glutathione reductase or superoxide dismutase activities. Liver catalase activities were decreased by nitrofurantoin at 4 hr. Lung GSH levels were increased whilst glutathione peroxidase activity was decreased at 4 and 24 hr. Lung glutathione reductase activity was reduced in certain groups. Nitrofurantoin did not affect lung superoxide dismutase, but catalase was decreased at 24 hr. Liver malondialdehyde levels were increased by nitrofurantoin in the vitamin E deficient group whilst lung malondialdehyde levels remained unchanged. Both liver and lung malondialdehyde levels were unaffected by vitamin E supplementation when compared to the vitamin E-sufficient group. These results suggest that nitrofurantoin (40 mg/kg) was deleterious to the liver and lung. Nitrofurantoin-induced lipid peroxidation was seen in vitamin E deficiency but an increase in dietary vitamin E content did not provide additional protection compared to the recommended daily allowance. The antioxidant acitivities of α-tocopherol and γ-enriched tocotrienol were similar.     

Influence of naringenin on oxytetracycline mediated oxidative damage in rat liver

Naringenin is a naturally occurring citrus flavanone, which has been reported to have a wide range of pharmacological properties. The present work was carried out to evaluate the effect of naringenin on antioxidant and lipid peroxidation status in liver of oxytetracycline-intoxicated rats. Intraperitonial administration of oxytetracycline 200 mg/kg for 15 days resulted a significant elevation in serum hepatospecific markers such as aspartate transaminase, alanine transaminase, alkaline phosphatase, lactate dehydrogenase, and bilirubin and the levels of lipid peroxidation markers (thiobarbituric acid reactive substances (TBARS) and lipid hydroperoxides) in liver. Oxytetracycline also caused a significant reduction in the activities of superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione (GSH), vitamin C and vitamin E in liver. Oral administration of naringenin (50 mg/kg b.w.t.) with oxytetracycline significantly decreased the activities of serum aspartate transaminase, alanine transaminase, alkaline phosphatase, lactate dehydrogenase and the levels of bilirubin along with significant decrease in the levels of lipid peroxidation markers in the liver. In addition, naringenin significantly increased the activities of superoxide dismutase, catalase and GSH peroxidase as well as the level of GSH, vitamin C and vitamin E in liver of the oxytetracycline-treated rats. Our results demonstrate that naringenin exhibited antioxidant property and decrease the lipid peroxidation against oxytetracycline-induced oxidative stress in liver.     

Effects of diallyl tetrasulfide on cadmium-induced oxidative damage in the liver of rats

The protective efficacy of diallyl tetrasulfide (DTS) from garlic on liver injury induced by cadmium (Cd) was investigated. In this study, Cd (3 mg/kg body weight) was administered subcutaneously for 3 weeks to induce toxicity. DTS was administered orally (10, 20 and 40 mg/kg body weight) for 3 weeks with subcutaneous (sc) injection of Cd. Cd-induced liver damage was evidenced from increased activities of serum hepatic enzymes, namely aspartate transaminase, alanine transaminase, alkaline phosphatase and lactate dehydrogenase, with significant elevation of lipid peroxidation indices (thiobarbituric acid reactive substances and hydroperoxides) and protein carbonyl groups in the liver. Rats subjected to Cd toxicity also showed a decline in the levels of total thiols, reduced glutathione (GSH), vitamin C and vitamin E, accompanied by an increased accumulation of Cd, and significantly decreased activities of superoxide dismutase, catalase (CAT), glutathione peroxidase, glutathione-S-transferase (GST), glutathione reductase, and glucose-6-phosphate dehydrogenase in the liver. Administration of DTS at 40 mg/kg body weight significantly normalised the activities of hepatic marker enzymes, compared to other doses of DTS (10 and 20 mg/kg body weight). In addition, DTS (40 mg/kg body weight) significantly reduced the accumulation of Cd and the level of lipid peroxidation, and restored the level of antioxidant defense in the liver. Histological studies also showed that administration of DTS to Cd-treated rats resulted in a marked improvement of hepatocytes morphology with mild portal inflammation. Our results suggest that DTS might play a vital role in protecting Cd-induced oxidative damage in the liver.     

The antioxidant role of pterostilbene in streptozotocin-nicotinamide-induced type 2 diabetes mellitus in Wistar rats

The antioxidant effect of pterostilbene on streptozotocin-nicotinamide-induced diabetic rats has been assessed. The activity of superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and reduced glutathione was significantly decreased in liver and kidney of diabetic animals when compared with normal control. There were significant improvements in these activities after treatment with pterostilbene at a dose of 40 mg kg(-1) for six weeks. The increased levels of lipid peroxidation measured as thiobarbituric acid reactive substances (TBARS) in liver and kidney of diabetic rats were also normalized by treatment with pterostilbene. Chronic treatment of pterostilbene remarkably reduced the pathological changes observed in liver and kidney of diabetic rats. These results indicated the antioxidant property of pterostilbene.     

Chemoprevention of N-nitrosodiethylamine induced phenobarbitol promoted liver tumors in rat by extract of Indigofera aspalathoides

The chemopreventive effect of ethanol extract of Indigofera aspalathoides (EIA) on N-nitrosodiethylamine (DEN, 200 mg/kg)-induced experimental liver tumor was investigated in male Wistar rats. Oral administration of ethanol extract of Indigofera aspalathoides (250 mg/kg) effectively suppressed liver tumor induced with DEN as revealed by decrease in the levels of extend of serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), alkaline phosphatase (ALP), total bilirubin, gamma glutamate transpeptidase (GGTP), lipid peroxidase (LPO), glutathione peroxidase (Gpx) and glutathione S-transferase (GST) with a concomitant increase in enzymatic antioxidant (superoxide dismutase and catalase) levels when compared to those in liver tumor bearing rats. The histopathological changes of liver sample were compared with respective control. Our results show a significant chemopreventive effect of EIA against DEN induced liver tumor.     

Prolonged phenobarbital pretreatment abolishes the early oxidative stress component induced in the liver by acute lindane intoxication

Lindane administration to rats (60 mg/kg b.w.) led to an enhancement in the oxidative stress status of the liver at 4 h after treatment, characterized by increases in hepatic thiobarbituric acid reactants (TBARS) formation and chemiluminescence, reduced glutathione (GSH) depletion, and diminution in the biliary content and release of GSH. These changes were observed in the absence of changes in either microsomal functions (cytochrome P450 content, NADPH-dependent superoxide radical production, and NADPH-cytochrome P450 reductase or NADPH oxidase activities) or in oxidative stress-related enzymatic activities (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase, and glutathione-S-transferases), over control values. Phenobarbital (PB) administration (0.1% in drinking water; 15 days) elicited an enhancement in liver microsomal functions, lipid peroxidation, and GSH content, without changes in oxidative stress-related enzymatic activities, except for the elevation in those of glutathione reductase and glutathione-S-transferase, compared to control rats. Lindane given to PB-pretreated rats did not alter liver microsomal functions, lipid peroxidation, glutathione status, or oxidative stress-related enzymatic activities, as compared to PB-pretreated animals. In addition, lindane induced periportal necrosis with hemorrhagic foci in untreated rats, but not in PB-pretreated animals. It is concluded that the early oxidative stress response of the liver to lindane and hepatic injury are suppressed by PB pretreatment via induction of microsomal enzymes in all zones of the hepatic acinus. reserved.     

Beneficial effect of hesperidin on lipopolysaccharide-induced hepatotoxicity

Hesperidin (HDN) is a flavanone glycoside abundantly found in citrus fruits. HDN has been reported to possess significant activities against allergy, haemorrhoids, hormonal disorders and ulcers. Other reported activities include anti-inflammatory, analgesic, antibacterial, antifungal, antiviral, antioxidant and free radical scavenger activity. A potentially important effect of endotoxin is the increased production of reactive oxygen intermediates as O(2)(-), peroxides and nitric oxide. The study reported here show a beneficial effect of HDN in amelioration of endotoxin-induced hepatic dysfunction and oxidative stress in the liver of rats. Hepatotoxicity was induced by administering lipopolysaccharide (LPS), in a single dose of 1mg/kg intraperitoneally to the rats. A marked hepatic dysfunction evident by rise in serum levels of liver enzymes (ALT, AST, ALP) and total bilirubin (p<0.05) was observed. Serum and tissue nitrite levels were also increased. LPS challenge further increased thiobarbituric acid reactive substances (TBARS) levels, whereas glutathione (GSH) content and superoxide dismutase (SOD) activity were decreased in the liver homogenates of the rats showing a marked oxidative stress. HDN administration successfully and dose dependently attenuated these effects of LPS. In conclusion, these findings suggest that HDN attenuates LPS-induced hepatotoxicity possibly by preventing cytotoxic effects of NO and oxygen free radicals.     

Arsenic-induced cell death in liver and brain of experimental rats

Arsenic is a well established human carcinogen and is ubiquitous in the environment. The present study demonstrates the effect of acute arsenic administration at three different doses in liver and brain of Wistar rats. Sodium arsenite was administered orally at doses of 6.3 mg/kg, 10.5 mg/kg and 12.6 mg/kg of body weight on the basis of a lethal dose 50% (LD50) for 24 hr. After administration of arsenites, liver and brain were analyzed for various parameters of oxidative stress, histopathological changes and caspase-3 activity. Glutathione levels were decreased significantly in the liver at all doses. In liver the following biochemical changes were observed, a significant lipid peroxidation and cytochrome-P450 induction along with significant decrease in catalase and superoxide dismutase was observed at 10.5 mg/kg and 12.6 mg/kg. The activity of glutathione peroxidase was increased significantly at all doses. In brain, no significant change was observed at 6.3 mg/kg. However, a significant increase in lipid peroxidation and glutathione peroxidase activity along with significant decrease in the activity of glutathione, catalase and superoxide dismutase was observed at 10.5 mg/kg and 12.6 mg/kg. The activity of glutathione-S-transferase was decreased significantly in both liver and brain at 10.5 and 12.6 mg/kg. No significant alteration in the activity of glucose-6-phosphate dehydrogenase and glutathione reductase was observed in either liver or brain at any dose. Dose-dependent histopathological changes, observed in both liver and brain are also described. A significant increase in caspase-3 activity was observed at all doses in liver and at 10.5 and 12.6 mg/kg in brain. Sodium arsenite caused DNA cleavage into fragments and manifested as "DNA laddering", a hallmark of apoptosis.     

Effects of aldose reductase inhibitors on antioxidant defense in rat and rabbit liver.

Aldose reductase has been implicated in the etiology of diabetic complications, atherosclerosis, and ischemia-reperfusion injury. Aldose reductase inhibitors are known to have species-dependent differences in biotransformation enzyme induction. Whether aldose reductase inhibitors, which have antioxidant potential, alter the oxidative stress pathway is unknown. This study has determined whether four daily ip treatments of either low (10 mg/kg) or high (50 mg/kg) doses of AL-1576 or AL-4114 alter the activities of the antioxidant defense enzymes catalase, glutathione reductase, glutathione peroxidase, superoxide dismutase, and the concentrations of reduced and oxidized glutathione in livers of normal rats and rabbits. There was no change in the concentration of thiobarbituric acid reactive substances in either rat or rabbit livers, indicating that lipid peroxidation was not increased by any treatment. Hepatic catalase, superoxide dismutase, and glutathione peroxidase activities and concentrations of reduced and oxidized glutathione were not significantly altered in rat, though glutathione reductase activity was increased after high doses of both drugs. However, in rabbit liver, glutathione reductase activity decreased in a dose-dependent manner after AL-4114 treatment, while superoxide dismutase and glutathione peroxidase activities decreased only after the low dose of AL-4114. Although AL-4114 and AL-1576 did not directly generate increased lipid peroxidation within normal rat and rabbit livers, some of the enzymes responsible for oxidative defense were altered, particularly in rabbit livers.     

Potential beneficial effect of naringenin on lipid peroxidation and antioxidant status in rats with ethanol‐induced hepatotoxicity

Objectives The aim was to study the effect of naringenin, a biologically active compound, on tissue 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 and 0.5% carboxymethyl cellulose; groups 3 and 4 received 20% ethanol equivalent to 6 g/kg daily for 60 days. In addition, groups 2 and 4 were given naringenin (50 mg/kg) daily for the last 30 days of the experiment. Key findings The results showed significantly elevated levels of serum aspartate and alanine transaminases, γ‐glutamyl transpeptidase, tissue thiobarbituric acid reactive substances, conjugated dienes, lipid hydroperoxides and protein carbonyl content, and significantly lowered activities/levels of antioxidants such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione‐S‐transferase, reduced glutathione and vitamins C and E in ethanol‐treated rats compared with control rats. Administration of naringenin to rats with ethanol‐induced liver injury significantly decreased the levels of serum aspartate and alanine transaminases, γ‐glutamyl transpeptidase, tissue thiobarbituric acid reactive substances, conjugated dienes, lipid hydroperoxides and protein carbonyl content and significantly elevated the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione‐S‐transferase, and the levels of reduced glutathione and vitamins C and E in the tissues compared with unsupplemented ethanol‐treated rats. Histological changes observed in the liver correlated with the biochemical findings. Conclusions Taken together these findings suggest that naringenin has a therapeutic potential in the abatement of ethanol‐induced hepatotoxicity.