Studies of methyl 2-nitroimidazole-1-acetohydroxamate (KIN-804) 1: effect on free radical scavenging system in mice bearing Ehrlich ascites carcinoma

Methyl 2-nitroimidazole-1-acetohydroxamate (KIN-804) is a 2-nitroimidazole derivative containing a hydroxamate side chain designed to enhance the radiosensitization response of hypoxic cells. The possible sensitization of tumor tissue by KIN-804 can be evaluated through investigation of the levels of the free radical scavengers; namely, glutathione (GSH) and its complex enzyme system including glutathione reductase (GR) and glutathione peroxidase (GSH-Px), as well as glucose-6-phosphate dehydrogenase (G-6-PD). Female albino mice were inoculated with Ehrlich carcinoma in the thigh. Administration of KIN-804 (i.p. 80 mg/kg body weight) was carried out 20 min before localized irradiation of 10 Gy. The data revealed that KIN-804 administration, followed or not by gamma irradiation, resulted in a significant decrease in GSH content in tumor tissues associated with inhibition in GR and G-6-PD activities. Blood GSH-Px was enhanced in tumor inoculated mice and the administration of KIN-804 returned it to the normal value. These changes were more noticeable in tumor bearing mice exposed to both KIN-804 and irradiation.     

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

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

Emblica officinalis aqueous extract ameliorates ochratoxin-induced lipid peroxidation in the testis of mice

The present study was undertaken to assess the ameliorative effect of Emblica officinalis aqueous extract on ochratoxin-induced lipid peroxidation in the testis of mice. Adult male albino mice were orally administered with 50 and 100 microg of ochratoxin (Groups 4, 5) in 0.2 mL olive oil/animal/day for 45 days. The results revealed a significant increase in LPO (lipid peroxidation) in the testis of mice treated with ochratoxin compared to that of vehicle control (Group 2). The levels of non-enzymatic antioxidants: GSH (glutathione) and TAA (total ascorbic acid) as well as enzymatic antioxidants: SOD (superoxide dismutase), CAT (catalase), GPX (glutathione peroxidase), GRX (glutathione reductase) and GST (glutathione transferase) were significantly decreased in the testis of ochratoxin-treated mice. Oral administration of Emblica officinalis aqueous extract (2 mg/animal/day) along with ochratoxin (Groups 6, 7) for 45 days, caused, significant, amelioration in ochratoxin-induced LPO by increasing the contents of non-enzymatic (GSH and TAA) and activities of enzymatic (SOD, CAT, GPX, GRX and GST) antioxidants in the testis of mice as compared with those given ochratoxin alone animals (Groups 4, 5). Thus, oral administration of Emblica officinalis aqueous extract along with ochratoxin significantly ameliorates ochratoxin-induced lipid peroxidation in the testis of mice.     

Effect of nitric oxide synthase inhibitors on lipid peroxide formation in liver caused by endotoxin challenge

This study investigated the effect of nitric oxide on lipid peroxide formation during endotoxaemia. Nitric oxide synthase inhibitors N(G)-monomethyl-L-arginine acetate (L-NMMA, 20 mg/kg, intravenously), N(G)-nitro-L-arginine-methyl ester (L-NAME, 10 mg/kg, intravenously), and N(G)-nitro-L-arginine (L-NA, 10 mg/kg, intravenously), and a relatively selective inducible nitric oxide synthase inhibitor aminoguanidine (10 mg/kg, intravenously), did not protect against endotoxin-induced death of mice. Superoxide dismutase activity in liver 18 hr after administration of endotoxin (6 mg/kg, intraperitoneally) to L-arginine analogues (L-NMMA, L-NAME, L-NA)-treated mice was lower than in mice treated with endotoxin alone, whereas the administration of L-arginine analogues increased xanthine oxidase activity in the livers of endotoxin-injected mice compared with mice treated with endotoxin alone. In mice treated with L-arginine analogues and aminoguanidine, the levels of non-protein sulfhydryl and lipid peroxide in liver 18 hr after endotoxin injection did not show significant differences from mice treated with endotoxin alone. L-Arginine analogues and aminoguanidine had little effect on lipid peroxide formation in liver caused by endotoxin. Treatment with aminoguanidine (300 microM) significantly inhibited endotoxin-induced intracellular peroxide in J774A.1 cells, however, aminoguanidine did not affect endotoxin-induced cytotoxicity in J774A.1 cells. Our results clearly demonstrate that treatment with catalase (10 microg/ml), D-mannitol (10 mM), or superoxide dismutase (100 U/ml), has little or no effect on nitric oxide production by endotoxin (1 microg/ml)-activated J774A.1 cells. These findings suggest that nitric oxide is not crucial for lipid peroxide formation during endotoxaemia. Therefore, it is unlikely that nitric oxide plays a significant role in liver injury caused by free radical generation in endotoxaemia.     

Efficacy of diphenyl diselenide against cerebral and pulmonary damage induced by cadmium in mice

This study was designed to examine if diphenyl diselenide (PhSe)(2), an organoselenium compound, attenuates pulmonar and cerebral oxidative stress caused by sub-chronic exposure to CdCl(2). Male adult Swiss albino mice received CdCl(2) (10 micromol/kg, subcutaneously), 5 times/week, for 4 weeks. (PhSe)(2) (10 micromol/kg or 20 micromol/kg, orally) was given concomitantly with CdCl(2) to mice. A number of toxicological parameters in lung and brain of mice were examined including delta-aminolevulinic acid dehydratase (delta-ALA-D), superoxide dismutase (SOD) and catalase activities, lipid peroxidation, non-protein thiols (NPSH) and ascorbic acid content. Na(+),K(+)-ATPase activity, acetylcholinesterase (AChE) activity, [(3)H]glutamate uptake and [(3)H]glutamate release were also carried out in brain. Cadmium concentration and histopathological analysis were carried out in lung tissue. (PhSe)(2) at the dose of 20 micromol/kg protected the inhibition of delta-ALA-D, SOD and CAT activities, the reduction of vitamin C content and the increase of lipid peroxidation levels caused by CdCl(2) in lungs. At 10 micromol/kg, (PhSe)(2) protected cerebral AChE and CAT activities inhibited by CdCl(2). There were no histopathological alterations in the lung of mice after CdCl(2) exposure. The pulmonary cadmium concentration was higher (2.8-fold) in the group exposed to CdCl(2) than in control mice. (PhSe)(2) at dose of 20 micromol/kg reduced cadmium concentration towards the control level. The results suggest that oral administration of (PhSe)(2) attenuated the oxidative damage induced by CdCl(2) in lung and brain of mice.     

Effect of cigarette smoke inhalation on antioxidant enzymes and lipid peroxidation in the rat

Inhalation of cigarette smoke significantly increased glutathione (GSH) content and increased lipid peroxidation without altering the activities of Superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px) or glutathione reductase (GR) in the lung (six male Wistar rats). Following intratracheal administration of benzo[a]pyrene (BP), an increase in pulmonary GSH-Px activity, GSH content and lipid peroxidation was observed after 12 h. GSH-Px activity and GSH content returned to control values by 7 and 30 days, respectively, whereas lipid peroxidation in the lung remained significantly greater than the control value for up to 7 days of BP administration. Hepatic activity of SOD was increased significantly, whereas the activities of GSH-Px, catalase, GR, and GSH content were not changed by inhalation of cigarette smoke. On administration of BP, a significant increase in the activities of SOD and GSH-Px was observed at 12 h. After 7 and 30 days, the activities of these antioxidant enzymes were comparable to their respective control group values. No change in the activity of catalase or in the level of lipid peroxidation was noted throughout the entire study period.     

The effects of desferrioxamine on cisplatin-induced lipid peroxidation and the activities of antioxidant enzymes in rat kidneys

Cisplatin-induced nephrotoxicity is associated with an increase in lipid peroxidation and oxygen free radicals in rat kidneys. In this study, the effects of desferrioxamine were compared to vitamin C and E on cisplatin-induced lipid peroxidation and antioxidant enzyme activities in rat kidneys. Rats were divided into five groups, with 15 Wistar rats in each group. In the control group, rats received 1 mL/100 g isotonic saline solution intraperitoneally (i.p.). In Group II, 10 mg/kg cisplatin i.p. was injected to rats. Thirty minutes before the same dosage of cisplatin administration, 100 mg/kg i.p. vitamin C or E was given to rats in groups III and IV, respectively. Rats in Group V received 250 mg/kg desferrioxamine i.p., before the same dose of cisplatin administration. All rats were killed by cervical dislocation after 72 hours. The kidneys were immediately removed and washed in cold saline. Spectrophotometric method was used for all analyses. While catalase, glutathione reductase (GR), and superoxide dismutase (SOD) levels were found to be significantly decreased (P < 0.001), malondialdehyde (MDA) (P < 0.05) and hydrogen peroxide (H2O2) (P < 0.001) levels were significantly increased in the cisplatin group when compared to the controls. MDA levels were decreased by desferrioxamine (P < 0.005) as well as vitamin C and E (P < 0.05 and P < 0.001, respectively). These three compounds induced a significant increase in SOD levels (P < 0.05), but only in the vitamin C group, were SOD levels not significantly different than the levels of the controls (P > 0.05). In the desferrioxamine (P < 0.05), vitamin C and E groups (P < 0.001 for both), the cisplatin elevated H2O2 levels were decreased. None of these drugs had any effect on GR and catalase levels (P > 0.05). Desferrioxamine is useful to prevent cisplatin-induced lipid peroxidation, however, vitamin C and E are more effective on antioxidant enzymes than desferrioxamine.     

Acute exposure to solar simulated ultraviolet radiation affects oxidative stress-related biomarkers in skin, liver and blood of hairless mice

The ultraviolet (UV) region of solar radiation is a critical factor in the initiation and development of a number of skin diseases. However, it is not only skin which is directly exposed to solar light that is affected by UV radiation, through low molecular weight mediators, generated upon irradiation, "non-skin" tissues can also be affected. The aim of this study was to examine in detail, the acute effects of UVA and UVB wavebands on hairless mice. Female SKH-1 hairless mice were exposed to a single dose of UVB (200, 800 mJ/cm(2)) or UVA (10, 20 J/cm(2)) using a solar simulator. The effects on haematological parameters, activity and/or expression of antioxidant enzymes, level of glutathione (GSH), markers of oxidative damage (lipid peroxidation and carbonylated proteins) were analysed in erythrocytes, plasma, liver and whole skin homogenates. No macroscopic changes were observed either 4 or 24 h after UVA/UVB exposure. The blood count showed a significant increase in leukocyte number and reduction of platelets 4 h following UVA and UVB irradiation, which disappeared 24 h after irradiation except for the higher UVA dose. Changes in oxidative stress-related parameters, particularly activity of catalase (CAT) and superoxide dismutase (SOD) and level of GSH and lipid peroxidation products, were found in skin, erythrocytes and liver. The expression of several enzymes (CAT, SOD, glutathione transferase (GST), nicotinamide adenine dinucleotide (phosphate) quinone oxidoreductase (NQO1) and hem oxygenase-1 (HO-1)) in skin was affected following UVA and UVB radiation. Increase in carbonylated proteins was found in plasma and skin samples.     

Effect of zinc on hepatic lipid peroxidation and antioxidative enzymes in ethanol-fed rats

A 3-ml aliquot of 30% ethanol was fed daily to normal as well as zinc-treated (227 mg l(-1)) rats for periods of 2, 4 and 8 weeks. A highly significant increase in the levels of hepatic lipid peroxidation was observed in ethanol-fed rats after 4 and 8 weeks of treatment. On the other hand, the levels of lipid peroxidation came down significantly following ethanol feeding to zinc-treated rats. The activities of glutathione peroxidase (GPx), catalase and superoxide dismutase (SOD) in liver were elevated significantly after ethanol administration to rats for durations of 2, 4 and 8 weeks. Interestingly, zinc treatment to rats given ethanol was able to bring down the elevated levels of SOD, catalase and GPx to within normal limits, However, zinc administration alone did not cause any significant alteration in the activities of these antioxidative enzymes.     

Heme oxygenase is the main protective enzyme in rat liver upon 6-day administration of cobalt chloride

Changes in the activities of rat liver heme oxygenase (HO), superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and glutathione reductase (GR), as well as changes in lipid peroxidation and reduced glutathione (GSH) levels were measured after acute loading and chronic administration of cobalt chloride (CoCl2). Acute loading was achieved by a single subcutaneous injection of 60 mg CoCl2/kg body weight for 24 h. Chronic administration was performed by giving the same total amount of CoCl2 in small doses over longer periods of time: 30 mg CoCl2/kg daily for 2 days, 15 mg CoCl2/kg daily for 4 days, or 10 mg CoCl2/kg daily for 6 days. The results showed that HO activity was increased both after acute loading (7-fold increase) and upon 6-day administration of CoCl2 (5-fold increase). The GSH level, 24 h after a single injection of CoCl2, was lower than that of the control animals. However, upon chronic administration of small doses CoCl2, the level of GSH increased and was accompanied by an increase in GR activity. Chronic administration of CoCl2 produced persistent oxidative stress, which was illustrated with a continuous increase in lipid peroxidation. At the same time, under these conditions, the activities of oxidative-stress-protective enzymes were either inhibited (SOD, catalase) or not significantly changed (GPx). Collectively, these findings suggest that the sustained up-regulation of HO activity in rat liver upon 6 day administration of CoCl2 would be beneficial by providing the cells with antioxidants, biliverdin and bilirubin, and together with the increased levels of GSH would act as a part of the defence mechanisms against the cobalt-induced oxidative stress.     

Evidence for free radical scavenging activity of Ashwagandha root powder in mice

The effects of Ashwagandha root powder (0.7 and 1.4 g/kg body weight/day), administered for 15 and 30 days, was investigated on lipid peroxidation (LPO), superoxide dismutase (SOD) and catalase (CAT) activities in mice. While 15 days treatment with Ashwagandha root powder did not produce any significant change, 30 days treatment produced a significant decrease in LPO, and an increase in both SOD and CAT. Our findings indicate that Ashwagandha root powder possesses free radical scavenging activity, which may be responsible for its pharmacological effects.     

The influence of ascorbic acid on nickel-induced hepatic lipid peroxidation in rats.

We studied the effect of oral ascorbic acid treatment on nickel sulfate-induced lipid peroxidation in the liver of Wistar strain male albino rats. Lipid peroxide and glutathione levels and the activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were estimated in liver. Nickel sulfate administration significantly increased the level of lipid peroxides and decreased glutathione, SOD, CAT, and GSH-Px activities in liver. The simultaneous administration of ascorbic acid with nickel sulfate resulted in a remarkable improvement of lipid peroxide, glutathione, SOD, CAT, and GSH-Px status in liver in comparison with rats treated with nickel alone. Nickel sulfate has an adverse effect on hepatic lipid peroxidation in animals, but simultaneous treatment with ascorbic acid offers a relative protection against nickel-induced hepatotoxicity.     

Effects of cianidanol on the blood lipid peroxide status in patients with chronic hepatitis

This study was designed to investigate the effect of the natural bioflavonoid compound cianidanol on the blood lipid peroxide status of patients with chronic hepatitis. Nine patients had chronic active liver disease--seven of them hepatitis B virus-positive--and five had chronic alcoholic hepatitis. Besides some biochemical liver function tests (serum bilirubin, aminotransferases and gamma-glutamyl transferase), the changes in the serum level of malondialdehyde (a thiobarbituric acid reactive substance) as one of the end-products of lipid peroxidation, as well as the quantity/or activity of enzymes controlling peroxidation (superoxide dismutase (SOD), glutathione peroxidase and catalase) were measured. In addition, the serum level of the natural antioxidant vitamin E was followed-up. Cianidanol treatment (at a dose of 3.0 g/day for one month and of 1.5 g/day for two months) resulted in a slight improvement in aminotransferases and a significant fall (normalization) of high serum malondialdehyde level. After a marked transient increase, serum SOD content decreased while glutathione peroxidase and catalase activities as well as the vitamin E blood level increased during the treatment. Results suggest that (cianidanol in vivo inhibits lipid peroxidation and influences antioxidant enzyme systems and vitamin E in the blood of patients with chronic hepatitis.     

羊栖菜多糖对L_(615)小鼠LPO含量及GR、GSH—PX、CAT和SOD活性的影向

本文报道了羊栖菜多糖(SFPS)对L_(615)小鼠全血及肝脾脂质过氧化物(LPO)含量以及对各胱甘肽还原酶(GR)、谷胱甘肽过氧化物酶(GSH—PX)、过氧化氢酶(CAT)、超氧化物歧化酶(SOD)等酶活性的影响。结果表明,SFPS可显著降低L_(615)小鼠全血及肝脾LPO的含量,增加CAT、SOD的酶活性,提示SFPS具有清除L_(615)小鼠体内自由基,抗脂质过氧化作用。本文结果提示,SFPS的这些作用可能是其抗白血病作用的机理之一。     

Role of Ca2+ on Endotoxin-Sensitivity by Galactosamine Challenge: Lipid Peroxide Formation and Hepatotoxicity in Zymosan-Primed Mice

Abstract: This study was investigated to clarify the role of intracellular Ca²⁺ following endotoxin treatment (1 mg/kg, intraperitoneally) to D-galactosamine-sensitized mice (400 mg/kg, intraperitoneally), and to observe lipid peroxide levels, an index of hepatotoxicity, in endotoxin/galactosamine (Ga1N)-challenged mice under activation of macrophages, especially Kupffer cells, by zymosan. The liver lipid peroxide level and serum glutamic pyruvic transminase activity in mice 18 hr after administration of endotoxin/Ga1N were markedly higher than those in mice treated only with endotoxin. In spite of an increase in lipid peroxide formation, there was little or no effect of Ga1N administration on xanthine oxidase and superoxide dismutase activities in mice given endotoxin. However, the injection of verapamil (10 mg/kg, subcutaneously) markedly decreased lipid peroxide levels in liver of endotoxin/Ga1N-injected mice. In the mice given a Ca²⁺-deficient diet, lipid peroxide level in liver after endotoxin/Ga1N injection was markedly decreased compared to that in mice fed a normal diet. Administration of dexamethasone (200 μg/kg, intraperitoneally) in mice 1 hr before treatment with endotoxin/Ga1N did not induce lipid peroxide formation. Administration of endotoxin to Ga1N-treated mice resulted in a higher level of liver cytosolic free Ca²⁺ ([Ca²⁺]_i) than that in endotoxin-treated mice. On the other hand, Ca²⁺-ATPase activity in liver plasma membrane in the endotoxin/Ga1N-treated mice was markedly decreased as compared with endotoxin alone. On the contrary, the Ca²⁺-ATPase activity in liver mitochondria was higher in endotoxaemic mice treated with Ga1N than in mice given endotoxin alone. State 3 respiration and respiratory control index, which are parameters of mitochondrial function, were decreased more in the liver of mice treated with endotoxin/Ga1N than in the endotoxin-treated group. These findings suggest that [Ca²⁺]_i may participate in the lipid peroxide formation which results from endotoxin/Ga1N-induced hepatotoxicity under conditions of zymosan-activated macrophages, and that the increases of endotoxin-sensitivity caused by Ga1N challenge may greatly contribute to Ca²⁺-mobilization in the hepatocyte.     

Antihyperglycaemic and antiperoxidative roles of acarbose in type 2 diabetes mellitus are possibly mediated through changes in thyroid function

1. The aim of the present study was to reveal the possible involvement of thyroid hormones in the antihyperglycaemic and antiperoxidative effects of acarbose. 2. The effects of acarbose on changes in serum concentration of thyroid hormones, insulin and glucose in dexamethasone-induced type 2 diabetic mice were investigated. Simultaneously, changes in lipid peroxidation (LPO), reduced glutathione (GSH) content and the activity of associated endogenous anti-oxidant enzymes, such as superoxide dismuatase (SOD) and catalase (CAT), were investigated in renal and cardiac tissues, which are commonly affected in diabetes mellitus. 3. Although administration of dexamethasone (1.0 mg/kg, i.m., for 22 days) caused hyperglycaemia with a parallel increase in serum insulin and tissue LPO, it decreased thyroid hormone concentrations and the activity of SOD and CAT. 4. When dexamethasone-induced hyperglycaemic mice were treated with acarbose (10 mg/kg per day, p.o., for 15 days), levels of thyroid hormones were increased and most of the abnormalities, including serum insulin and glucose levels, tissue LPO, SOD and CAT activity and GSH content, were reversed. 5. These findings suggest the involvement of thyroid hormones in the mode of action of acarbose in amelioration of type 2 diabetes mellitus.     

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

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

Peroxisome proliferation due to di (2-ethylhexyl) adipate, 2-ethylhexanol and 2-ethylhexanoic acid

The dose-response relationships for peroxisome proliferation due to Di (2-ethylhexyl) adipate (DEHA), 2-ethylhexanol (EH), 2-ethylhexanoic acid (EHA) have been investigated in rats and mice. Linear dose-response relationships were observed for induction of cyanide-insensitive palmitoyl CoA oxidation (PCO), used as a enzyme marker of peroxisome proliferation, by DEHA, EH and EHA in both species. Relative liver weights were also increased in a dose related manner. On a molar basis, DEHA was twice as potent as EH or EHA which were equipotent and PCO was stimulated to a greater extent in male mice than in rats or female mice. At doses above 8 mmol/kg/day, EH was toxic to rats (both sexes) and similarly EHA at 13.5 mmol/kg/day lead to the death of female rats. In a attempt to explain the species difference in carcinogenicity of DEHA previously reported, we also used Fischer 344 rats and B6C3F1 mice. DEHA administration (2.5 g/kg/day) to Fischer 344 rats and B6C3F1 mice lead to toxicity in female rats. Relative liver weights were increased in a dose related fashion by DEHA administration to both rats and mice, PCO but not catalase was markedly increased (up to 15 fold in male rats). Light microscopy examination indicated some glycogen loss, a dose related hypertrophy and increased eosinophilia in both rats and mice. Electron microscopy confirmed peroxisome proliferation accompanied by a marked reduction of lipid in the centrilobular hepatocytes. These data suggest EHA to be the proximate peroxisome proliferator derived from DEHA. These data indicate a higher sensitivity for Fischer 344 rats than B6C3F1 mice to hepatic peroxisome proliferation due to DEHA and ratio of PCO activity and catalase activity data suggest that more hydrogen peroxide (H₂O₂) could escape from peroxisomes in male Fischer 344 rats than B6C3F1 mice. These data obtained with B6C3F1 mice and Fischer 344 rats are not agreement with the carcinogenicity bioassays previously reported showing an incidence of hepatic tumours only in B6C3F1 mice.     

Effect of Indigofera aspalathoides on complete Freund’s adjuvant-induced arthritis in rats

The effect of ethanol extract of stems of Indigofera aspalathoides Vahl (Papilionaceae) (EIA) was evaluated for anti-arthritic activity on complete Freund’s adjuvant-induced (CFA-induced) arthritis in rats. The EIA was administered orally at doses of 250 and 500?mg/kg daily for 30 days. The paw volume was measured on days 7, 14, 21 and 30. At the end of day 30, the rats were sacrificed and various biochemical parameters such as serum aspartate transaminase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total cholesterol and triglycerides were estimated. Antioxidant enzymes, such as superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and lipid peroxide (LPO) in the liver and kidney of normal, arthritic control and EIA treated rats were studied. Oral administration of EIA effectively inhibits rat paw edema in a dose-dependent manner. EIA significantly (P?<0.01) altered the biochemical parameters which were affected in arthritic rats. There was significant alteration in LPO, SOD, catalase, and GPx levels when compared to arthritic control rats. Our findings showed a significant anti-arthritic effect of EIA against CFA-induced arthritis in rats.     

Effect of cisplatin on the activities of enzymes which protect against lipid peroxidation.

Increases in lipid peroxide in kidneys of rats treated with cisplatin were examined in relation to decreases in the activities of Cu,Zn-superoxide dismutase (Cu,Zn-SOD), Mn-SOD, glutathione peroxidase (GSHpx), glutathione S-transferase (GST) and catalase. The activities of catalase, GSHpx and GST in the kidney and the liver were significantly decreased after cisplatin administration. The decrease of GST activity in the kidney was 87.3%, this was the largest decrease among these enzymes in the tissues examined. Cu,Zn-SOD activity significantly decreased only in the kidney. In contrast, the activities of these enzymes in the heart and the lung, which showed no increase in lipid peroxide in our previous study, were not significantly decreased. Cisplatin does not directly increase lipid peroxidation in vitro; therefore, the increase of lipid peroxide in the kidneys of these rats treated with cisplatin can be attributed to a decrease in the activities of lipid peroxide-protecting enzymes.