A comparison of hepatoprotective activities of aminoguanidine and N-acetylcysteine in rat against the toxic damage induced by azathioprine

Azathioprine (AZA) is an important drug used in the therapy of autoimmune system disorders. It induces hepatotoxicity that restricts its use. The rationale behind this study was the proven efficacy of N-acetylcysteine (NAC; a replenisher of sulfhydryls) and reports on the antioxidant potential of aminoguanidine (AG; an iNOS inhibitor), that might be useful to protect against the toxic implications of AZA. AG (100 mg/kg; i.p.) or NAC (100 mg/kg; i.p.) were administered to the Wistar male rats for 7 days and after that AZA (15 mg/kg, i.p.) was given as a single dose. This caused an increase in the activity of hepatic aminotransferases (AST and ALT) in the serum 24 h after AZA treatment. AZA (7.5 or 15 mg/kg, i.p.) also caused an increase in rat liver lipid peroxides and a lowering of reduced glutathione (GSH) contents. In the other part of experiment, protective effects of AG and NAC were observed on AZA induced hepatotoxicity. NAC significantly protected against the toxic effects produced by AZA. Pretreatment with NAC prevented any change in the activities of both the aminotransferases after AZA. This pretreatment also resulted in a significant decline in the contents of lipid peroxides and a significant elevation in GSH level was evident after AZA treatment. In the group with AG pretreatment the activities of AST and ALT did not increase significantly after AZA when compared to control. However, the lipid peroxides and GSH levels did not have any significant difference when compared to AZA group. These observations also indicate that the improvement in the GSH levels by NAC is the most significant protective mechanism rather than any other mechanistic profile. The protective effect of AG against the enzyme leakage seems to be through the liver cell membrane permeability restoration and is independent of any effects on liver GSH contents.     

Protective effects of the apigenin-O/C-diglucoside saponarin from Gypsophila trichotoma on carbone tetrachloride-induced hepatotoxicity in vitro/in vivo in rats

This study investigated the hepatoprotective activity of saponarin, isolated from Gypsophila trichotoma Wend., using in vitro/in vivo hepatotoxicity model based on carbone tetrachloride (CCl₄)-induced liver damage in male Wistar rats. The effect of saponarin was compared with those of silymarin. In vitro experiments were carried out in primary isolated rat hepatocytes. Cell incubation with CCl₄ (86 μmol l⁻¹) led to a significant decrease in cell viability, increased LDH leakage, decreased levels of cellular GSH and elevation in MDA quantity. Cell pre-incubation with saponarin (60–0.006 μg/ml) significantly ameliorated CCl₄-induced hepatic damage in a concentration-dependent manner. These results were supported by the following in vivo study. Along with decreased MDA quantity and increased level of cell protector GSH, seven day pre-treatment of rats with saponarin (80 mg/kg bw; p.o.) also prevented CCl₄ (10%, p.o.)-caused oxidative damage by increasing antioxidant enzyme activities (CAT, SOD, GST, GPx, GR). Biotransformation phase I enzymes were also assessed. Administered alone, saponarin decreased EMND and AH activities but not at the same extent as CCl₄ did. However, pre-treatment with saponarin significantly increased enzyme activities in comparison to CCl₄ only group. The observed biochemical changes were consistent with histopathological observations where the hepatoprotective effect of saponarin was comparative to the effects of the known hepatoprotecor silymarin. Our results suggest that saponarin, isolated from Gypsophila trichotoma Wend., showed in vitro and in vivo hepatoprotective and antioxidant activity against CCl₄-induced liver damage.     

Potentiation in the intact rat of the hepatotoxicity of acetaminophen by 1,3-bis(2-chloroethyl)-1-nitrosourea

Studies of the killing of cultured hepatocytes by acetaminophen indicate that the cells are injured by an oxidative stress that accompanies the metabolism of the toxin (J. L. Farber et al. (1988) Arch. Biochem. Biophys. 267, 640-650). The present report documents that the essential features of the killing of cultured hepatocytes by acetaminophen are reproduced in the intact animal. Male rats had no evidence of liver necrosis 24 h after administration of up to 1000 mg/kg of acetaminophen. Induction of mixed function oxidase activity by 3-methylcholanthrene increased the hepatotoxicity of acetaminophen. Inhibition of glutathione reductase by 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) potentiated the hepatotoxicity of acetaminophen in male rats induced with 3-methylcholanthrene. Whereas the pretreatment with BCNU reduced the GSH content by 40%, a comparable depletion of GSH by diethylmaleate did not potentiate the toxicity of acetaminophen. The antioxidant diphenylphenylenediamine (25 mg/kg) and the ferric iron chelator deferoxamine (1000 mg/kg) prevented the liver necrosis produced by 500 mg/kg acetaminophen in rats pretreated with BCNU. Neither protective agent prevented the fall in GSH produced by acetaminophen. It is concluded the conditions of the irreversible injury of cultured hepatocytes by acetaminophen previously reported are not necessarily different from those that obtain in the intact rat with this toxin.     

Molecular and biochemical investigations on the effect of quercetin on oxidative stress induced by cisplatin in rat kidney

The present study was aimed to investigate the ability of quercetin (QE) to ameliorate adverse effects of cisplatin (Cis.) on the renal tissue antioxidants by investigating the kidney antioxidant gene expression and the antioxidant enzymes activity. Forty rats divided into. Control rats. QE treated rats were orally administered 100 mg QE/kg for successive 30 days. Cis. injected rats were administered i.p. Cis. (12 mg/kg b.w.) for 5 mutual days. Cis. + QE rats were administered Cis. i.p. (12 mg/kg) and orally administered 100 mg QE/kg for consecutive 30 days. The obtained results indicated that Cis. induced oxidative stress in the renal tissue. That was through induction of free radical production, inhibition of the activity of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR) as well their genes expression. At the same time, vitamin E, vitamin C and reduced glutathione (GSH) levels were decreased. QE had the ability to overcome cisplatin-induced oxidative stress through the reduction of free radical levels. The antioxidant genes expression and antioxidant enzymes activity were induced. Finally the vitamin E, vitamin C and GSH levels were increased. Our work, proved the renoprotective effects of QE against oxidative stress induced by cisplatin.     

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

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

Protection against cisplatin-induced nephrotoxicity by Cu(II)2(3,5-diisopropylsalicylate)4

The ability of Cu(II)(2)(3,5-diisopropylsalicylate)(4), CuDIPS, which exhibits superoxide dismutase (SOD)-like activity, to prevent cisplatin-induced nephrotoxicity was examined in rats. Rats were divided into four groups and treated as follows: (i) vehicle control; (ii) cisplatin (16 mg/kg, intraperitoneally); (iii) CuDIPS (10 mg/kg, intraperitoneally); and (iv) cisplatin plus CuDIPS. Rats were sacrificed 3 days post-treatment. Cisplatin alone resulted in significantly increased plasma creatinine and urea. Administration of 10 mg/kg CuDIPS prevented the cisplatin-induced elevation of plasma creatinine and urea and protected against kidney damage. Relative to controls, rats that received cisplatin treatment displayed a decrease of reduced glutathione (GSH) and elevated platinum and thiobarbituric acid reactive substances (TBARS) levels in the kidney. In comparison with controls, activities of antioxidant enzymes (SOD, CAT, GSH-Px and GSH-Rd) were also reduced in the kidney of rats treated with cisplatin. Administration of 10 mg/kg CuDIPS prevented cisplatin-induced alterations in renal platinum, GSH, TBARS, and antioxidant enzyme activities. This study suggests that the protection offered by CuDIPS against cisplatin-induced nephrotoxicity is partly related to maintenance of renal antioxidant systems.     

Hepatotoxic effects of acetaminophen. Protective properties of tryptophan derivatives

Rat intoxication with acetaminophen (APAP) (500–1500 mg/kg body weight, intragastrically) caused a considerable dose-dependent decrease in reduced glutathione (GSH) level in both liver cell cytoplasm and mitochondria (at the dose 1500 mg/kg body weight by 60% and 33%, respectively). The decrease in cytoplasmic GSH level was more pronounced than in mitochondria. Despite of significant mitochondrial GSH depletion we did not observe any inactivation of the mitochondrial enzymes: succinate dehydrogenase, α-ketoglutarate dehydrogenase, glutathione peroxidase, and also any decrease in the respiratory activity of liver mitochondria isolated from APAP-intoxicated rats. We have investigated hepatoprotector properties of tryptophan derivatives, melatonin and N-acetyl-nitrosotryptophan (a nitric oxide donor). The pineal gland hormone, melatonin, a known antioxidant (10 mg/kg body weight), did not prevent intramitochondrial GSH, but decreased the APAP hepatotoxicity evaluated as the decrease in the activity of marker enzymes of hepatic damage, ALT and AST and total bilirubin content in blood plasma of intoxicated rats, whereas NNT did not exhibit any hepatoprotective effects.     

Zinc Deficiency and Oxidative Stress Involved in Valproic Acid Induced Hepatotoxicity: Protection by Zinc and Selenium Supplementation

Valproic acid (VPA) is an antiepileptic drug, which its usage is limited due to its hepatotoxicity. The present study was conducted to investigate the efficacy of zinc (Zn) and selenium (Se), necessary trace elements, against VPA-induced hepatotoxicity in Wistar rats. The animals were divided into five groups: control, VPA 200 mg/kg, VPA + Zn (100 mg/kg), VPA + Se (100 mg/kg), and VPA + Zn + Se. The administration of VPA for four consecutive weeks resulted in decrease in serum level of Zn in rats. Also, an increase in liver marker enzymes (ALT and AST) and also histological changes in liver tissue were shown after VPA administration. Oxidative stress was evident in VPA group by increased lipid peroxidation (LPO), protein carbonyl (PCO), glutathione (GSH) oxidation, and reducing total antioxidant capacity. Zn and Se (100 mg/kg) administration was able to protect against deterioration in liver enzyme, abrogated the histological change in liver tissue, and suppressed the increase in oxidative stress markers. Zn and combination of Zn plus Se treatment showed more protective effects than Se alone. These results imply that Zn and Se should be suggested as effective supplement products for the prevention of VPA-induced hepatotoxicity.     

Hepatoprotective activity of quercetin against acrylonitrile-induced hepatotoxicity in rats

Acrylonitrile is a potent hepatotoxic, mutagen, and carcinogen. A role for free radical-mediated lipid peroxidation in the toxicity of acrylonitrile has been suggested. The present study was designed to assess the hepatoprotective effect of quercetin against acrylonitrile-induced hepatotoxicity in rats. Liver damage was induced by oral administration of acrylonitrile (50 mg/kg/day/5 weeks). Acrylonitrile produced a significant elevation of malondialdehyde (138.9%) with a marked decrease in reduced glutathione (72.4%), and enzymatic antioxidants; superoxide dismutase (81%), and glutathione peroxidase (53.2%) in the liver. Serum aspartate aminotransferase, alanine aminotransferases, direct bilirubin, and total bilirubin showed a significant increase in acrylonitrile alone treated rats (115.5%, 110.8%, 1006.8%, and 1000.8%, respectively). Pretreatment with quercetin (70 mg/kg/day/6 weeks) and its coadministration with acrylonitrile prevented acrylonitrile-induced alterations in hepatic lipid peroxides and enzymatic antioxidants as well as serum aminotransferases and bilirubin. Histopathological findings supported the biochemical results. We suggest that querectin possess hepatoprotective effect against acrylonitrile-induced hepatotoxicity through its antioxidant activity.     

Protective effect of Piper longum L. on oxidative stress induced injury and cellular abnormality in adriamycin induced cardiotoxicity in rats

Effect of methanolic extract of fruits of P. longum (PLM) on the biochemical changes, tissue peroxidative damage and abnormal antioxidant levels in adriamycin (ADR) induced cardiotoxicity in Wistar rats was investigated. PLM was administered to Wistar albino rats in two different doses, by gastric gavage (250 mg/kg and 500 mg/kg) for 21 days followed by ip ADR (15 mg/kg) on 21st day. ADR administration showed significant decrease in the activities of marker enzymes aspartate transaminase, alanine transaminase, lactate dehydrogenase and creatine kinase in heart with a concomitant increase in their activities in serum. A significant increase in lipid peroxide levels in heart of ADR treated rats was also observed. Pretreatment with PLM ameliorated the effect of ADR on lipid peroxide formation and restored activities of marker enzymes. Activities of myocardial antioxidant enzymes like catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase along with reduced glutathione were significantly lowered due to cardiotoxicity in rats administered with ADR. PLM pretreatment augmented these endogenous antioxidants. Histopathological studies of heart revealed degenerative changes and cellular infiltrations in rats administered with ADR and pretreatment with PLM reduced the intensity of such lesions. The results indicate that PLM administration offers significant protection against ADR induced oxidative stress and reduces the cardiotoxicity by virtue of its antioxidant activity.     

Alterations in susceptibility to carbon tetrachloride toxicity and hepatic antioxidant/detoxification system in streptozetocin-induced short-term diabetic rats: Effects of insulin and Schisandrin B treatment

The streptozotocin-induced short-term (2 week) diabetic rats showed an increase in susceptibility to carbon tetrachloride (CCl4)-induced hepatocellular damage. This diabetes-induced change was associated with a marked impairment in the hepatic glutathione antioxidant/detoxification response to CCl₄ challenge, as indicated by the abrogation of the increases in hepatic reduced glutathione (GSH) level, glucose-6-phosphate dehydrogenase and microsomal glutathione S-transferases (GST) activities upon challenge with increasing doses of CCl₄. While the hepatic GSH level was increased in diabetic rats, the hepatic mitochondrial GSH level and Se-glutathione peroxidase activity were significantly reduced. Insulin treatment could reverse most of the biochemical alterations induced by diabetes. Both insulin and schisandrin B (Sch B) pretreatments protected against the CCl₄ hepatotoxicity in diabetic rats. The hepatoprotection was associated with improvement in hepatic glutathione redox status in both cytosolic and mitochondrial compartments, as well as the increases in hepatic ascorbic acid level and microsomal GST activity. The ensemble of results suggests that the diabetes-induced impairment in hepatic mitochondrial glutathione redox status may at least in part be attributed to the enhanced susceptibility to CCl4 hepatotoxicity. Sch B may be a useful hepatoprotective agent against xenobiotics-induced toxicity under the diabetic conditions. (Mol Cell Biochem 175: 225–232, 1997)     

Prevention of chemically induced mammary tumorigenesis by daidzein in pre-pubertal rats: the role of peroxidative damage and antioxidative enzymes

Isoflavones are biologically active plant derived compounds that have several health promoting effects. In the present study hitherto unknown effects of one of the well known isoflavonoids, daidzein, has been evaluated on its chemo-preventive action against breast cancers in pre-pubertal rats. Either daidzein (500 μg/g bwt) or vehicle, dimethyl sulphoxide (DMSO), was administered at 16th, 18th, and 20th day post-partum and the chemopreventive efficacy was evaluated in dimethylbenz[a]nthracene (DMBA) induced Sprague-Dawley rats, at 50th day. To elucidate the mechanism of action, the antioxidative status was also examined in the liver and mammary gland of prebubertal rats using two different doses of daidzein (0.5 mg/kg bwt and 50 mg/kg bwt, p.o.) for 10 days. The specific activity of antioxidant enzymes as well as reduced glutathione (GSH) level and peroxidative damage were evaluated spectrophotometrically, both in liver as well as in mammary gland. Animals treated with daidzein pre-pubertally, showed a significant reduction in the tumorigenesis of mammary gland up to 37.4% as compared to animals induced for tumors with DMBA. In animals treated with 50 mg/kg of daidzein, a significant increase in the specific activities of the antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione transferase (GST), DT-diaphorase (DTD), and in GSH content were observed in both liver and mammary gland. Expectedly, the specific activity of lactate dehydrogenase (LDH) and level of peroxidative damage was decreased, as compared to that of control group of animals. Our results suggest that, daidzein can be considered as a potent chemopreventive agent against mammary carcinogenesis in pre-pubertal animals, with modulation of antioxidant enzymes being one of its mechanisms of actions.     

Antioxidant activity of medicinal herb Rhodococcum vitis-idaea on galactosamine-induced liver injury in rats.

Aim of the study was to evaluate in vivo antioxidant action of medicinal herb Rhodococcum vitis-idaea (Rh.v) on galactosamine (GalN)-induced rat liver toxicity. The results showed that the hepatotoxicity and oxidative stress induced by GalN (700 mg/kg, s.c.) after 24 h evidenced by an increase in serum alanine aminotransferase and glutathione (GSH) S-transferase activities, and lipid peroxidation in liver homogenate were significantly inhibited, when 10 times diluted Rh.v. extract (5 ml/kg, i.p.) was given to rats 12 and 1 h before GalN treatment demonstrating that the extract of Rh.v is a potent antioxidant and protective against GalN-induced hepatotoxicity. The main antioxidant compound of the herb water extract used in the experiment was determined as arbutin, which possess 8% of dry weight of the herb. The electron spin resonance (ESR) spectrometer analysis revealed that the arbutin isolated from Rh.v exhibited strong superoxide and hydroxyl radical scavenging ability.     

Silymarin modulates Cisplatin-induced oxidative stress and hepatotoxicity in rats

Cisplatin (CDDP) is a widely used anticancer drug, but at high dose, it can produce undesirable side effects such as hepatotoxicity. Because silymrin has been used to treat liver disorders, the protective effect of silymarin on CDDP-induced hepatotoxicity was evaluated in rats. Hepatotoxicity was determined by changes in serum alanine aminotransferase [ALT] and aspartate aminotransferase [AST], nitric oxide [NO] levels, albumin and calcium levels, and superoxide dismutase [SOD], glutathione peroxidase [GSHPx] activities, glutathione content, malondialdehyde [MDA] and nitric oxide [NO] levels in liver tissue of rats. Male albino rats were divided into four groups, 10 rats in each. In the control group, rats were injected i.p. with 0.2 ml of propylene glycol in saline 75/25 (v/v) for 5 consecutive days [Silymarin was dissolved in 0.2 ml of propylene glycol in saline 75/25 v/v]. The second group were injected with CDDP (7.5 mg /kg, I.P.), whereas animals in the third group were i.p. injected with silymarin at a dose of 100 mg/kg/day for 5 consecutive days. The Fourth group received a daily i.p. injection of silymarin (100 mg/kg/day for 5 days) 1 hr before a single i.p. injection of CDDP (7.5 mg/kg). CDDP hepatotoxicity was manifested biochemically by an increase in serum ALT and AST, elevation of MDA and NO in liver tissues as well as a decrease in GSH and the activities of antioxidant enzymes, including SOD, GSHPx in liver tissues. In addition, marked decrease in serum NO, albumin and calcium levels were observed. Serum ALT, AST, liver NO level, MDA was found to decreased in the combination group in comparison with the CDDP group. The activities of SOD, GSHPx, GSH and serum NO were lower in CDDP group than both the control and CDDP pretreated with silymarin groups. The results obtained suggested that silymarin significantly attenuated the hepatotoxicity as an indirect target of CDDP in an animal model of CDDP-induced nephrotoxicity.     

Antioxidant and hepatoprotective actions of medicinal herb, Terminalia catappa L. from Okinawa Island and its tannin corilagin

The antioxidant and hepatoprotective actions of Terminalia catappa L. collected from Okinawa Island were evaluated in vitro and in vivo using leaves extract and isolated antioxidants. A water extract of the leaves of T. catappa showed a strong radical scavenging action for 1,1-diphenyl-2-picrylhydrazyl and superoxide (O(2)(.-)) anion. Chebulagic acid and corilagin were isolated as the active components from T. catappa. Both antioxidants showed a strong scavenging action for O(2)(.-) and peroxyl radicals and also inhibited reactive oxygen species production from leukocytes stimulated by phorbol-12-myristate acetate. Galactosamine (GalN, 600 mg/kg, s.c.,) and lipopolysaccharide (LPS, 0.5 microg/kg, i.p.)-induced hepatotoxicity of rats as seen by an elevation of serum alanine aminotransferase, aspartate aminotransferase and glutathione S-transferase (GST) activities was significantly reduced when the herb extract or corilagin was given intraperitoneally to rats prior to GalN/LPS treatment. Increase of free radical formation and lipid peroxidation in mitochondria caused by GalN/LPS treatment were also decreased by pretreatment with the herb/corilagin. In addition, apoptotic events such as DNA fragmentation and the increase in caspase-3 activity in the liver observed with GalN/LPS treatment were prevented by the pretreatment with the herb/corilagin. These results show that the extract of T. catappa and its antioxidant, corilagin are protective against GalN/LPS-induced liver injury through suppression of oxidative stress and apoptosis.     

Modulation of glutathione and antioxidant enzymes by Ocimum sanctum and its role in protection against radiation injury

Aqueous extract (OE) of the leaves of Ocimum sanctum, the Indian holy basil, has been found to protect mouse against radiation lethality and chromosome damage and to possess significant antioxidant activity in vitro. Therefore a study was conducted to see if OE protects against radiation induced lipid peroxidation in liver and to determine the role, if any, of the inherent antioxidant system in radioprotection by OE. Adult Swiss mice were injected intraperitoneally (i.p.) with 10 mg/kg of OE for 5 consecutive days and exposed to 4.5 Gy of gamma radiation 30 min after the last injection. Glutathione (GSH) and the antioxidant enzymes glutathione transferase (GST), reductase (GSRx), peroxidase (GSPx) and superoxide dismutase (SOD), as well as lipid peroxide (LPx) activity were estimated in the liver at 15 min, 30 min, 1, 2, 4 and 8 hr post-treatment. LPx was also studied after treatment with a single dose of 50 mg/kg of OE with/without irradiation. OE itself increased the GSH and enzymes significantly above normal levels whereas radiation significantly reduced all the values. The maximum decline was at 30-60 min for GSH and related enzymes and at 2 hr for SOD. Pretreatment with the extract checked the radiation induced depletion of GSH and all the enzymes and maintained their levels within or above the control range. Radiation significantly increased the lipid peroxidation rate, reaching a maximum value at 2 hr after exposure (approximately 3.5 times that of control). OE pretreatment significantly (P < 0.0001) reduced the lipid peroxidation and accelerated recovery to normal levels. The results indicate that Ocimum extract protects against radiation induced lipid peroxidation and that GSH and the antioxidant enzymes appear to have an important role in the protection.     

Protective effect of proanthocyanidins against doxorubicin‐induced nephrotoxicity in rats

Doxorubicin (DOX) exerts toxic effects in several organs particularly kidney. The present study aimed to assess the protective effect of proanthocyanidins (PAs) against DOX‐induced nephrotoxicity in rats. A single dose of DOX (7.5 mg/kg, i.v.) significantly increased kidney weight, kidney/body weight ratio, serum urea, creatinine, tumor necrosis factor alpha levels, and kidney contents of malondialdehyde, nitric oxide, cyclooxygenase‐2, and caspase‐3 activity with significant reduction in final body weight, serum albumin, kidney contents of reduced glutathione (GSH), and superoxide dismutase activity as compared with control group. In contrast, pretreatment with PAs (200 mg/kg, p.o.) for 14 days before DOX and for 7 days after DOX ameliorated kidney function and oxidative stress parameters. Histopathological evidence confirmed the protective effects of PAs from the tissue damage induced by DOX. In conclusion, PAs have a multi‐nephroprotective effect that might be attributed to its antioxidant, anti‐inflammatory, and antiapoptoic activities.     

Effects of Bacillus thuringiensis toxin on hepatic lipid peroxidation and free-radical scavengers in rats given alpha-tocopherol or acetylsalicylate

The effect of Dipel (D), a Bacillus thuringiensis-based bioinsecticide, on hepatic antioxidant enzyme activities and lipid peroxidation in rat liver was investigated. Administration of D in a dose of 1 mg/100 g body mass for 4 successive days increased the activities of glutathione peroxidase (GPx), glutathione reductase (GR) and the level of malondialdehyde (MDA) in rat hepatocytes. The activity of superoxide dismutase (SOD) and glutathione (GSH) level were decreased. Administration of D in rats pretreated with alpha-tocopherol (alphaT) or acetylsalicylic acid (ASA) decreased the activities of GPx, GR and MDA levels, while the GSH level was increased compared with rats treated with D alone. The SOD activity was increased in rats pretreated with alphaT before D, but decreased on pretreatment with ASA, compared with rats treated with D alone. The results indicated that D induced oxidative stress in rat liver that has been protected by prior administration of alphaT or ASA.     

Cytoprotective effects of carvedilol against oxygen free radical generation in rat liver

The protective effects of carvedilol, an antihypertensive agent, against oxidative injury caused by acetaminophen were studied in rat liver. Male Wistar rats (250 +/- 30 g) were pre-treated with carvedilol (3.6 mg/kg, p.o.) for 10 days and on the 11th day received an overdose of acetaminophen (800 mg/kg, p.o.). Four hours after acetaminophen administration, blood was collected to determine serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). After that, rats were killed and the livers were excised to determine reduced glutathione (GSH), thiobarbituric acid reactive substances (TBARS) and carbonyl protein contents, and the activity of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione S-transferase (GST), and also the DNA damage index. Acetaminophen significantly increased the levels of TBARS, the DNA damage and SOD, AST and ALT activities. Carvedilol was able to prevent lipid peroxidation, protein carbonilation and DNA fragmentation caused by acetaminophen. Moreover, this drug prevented increases in SOD, AST and ALT activities. These results show that carvedilol exerts cytoprotective effects against oxidative injury caused by acetaminophen in rat liver. These effects are probably related to the O2*- scavenging property of carvedilol or its metabolites.     

Chemopreventive potential of luteolin during colon carcinogenesis induced by 1,2-dimethylhydrazine

We investigated the chemopreventive potential of luteolin on hepatic and circulatory lipid peroxidation and antioxidant status during 1,2-dimethylhydrazine induced colon carcinogenesis in rats. Rats were given a weekly subcutaneous injection of DMH at a dose of 20 mg/kg body weight for 15 weeks. Luteolin (0.2 mg/kg body weight/everyday p.o.) was given at the initiation and also at the postinitiation stages of carcinogenesis to DMH treated rats. The animals were sacrificed at the end of 30 weeks. Enhanced lipid peroxidation in the liver and circulation of tumor bearing rats was accompanied by a significant decrease in the levels of plasma and hepatic reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione-S-transferase (GST), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), vitamin C, vitamin E and beta-carotene in DMH treated rats as compared to the control rats. Intragastric administration of luteolin (0.2mg/kg body weight) to DMH-treated rats significantly reduced the incidence and size of tumor in the colon, reduced lipid peroxidation levels and enhanced the plasma and hepatic activities of GSH, GPx, GST, GR, SOD, CAT, vitamin C, vitamin E and beta-carotene. Thus the chemopreventive efficacy of luteolin against colon carcinogenesis is evidenced by our preliminary studies which showed decreased incidence of tumors and the antiperoxidative and antioxidant effect of luteolin. Further study on the exact mechanism of action of luteolin in preventing colon carcinogenesis is yet to be elucidated.