Elangovan Selvakumar

Mitigation of oxidative stress in cyclophosphamide-challenged hepatic tissue by DL-α-lipoic acid

The present study investigated the protective effect of DL-α-lipoic acid on the tissue peroxidative damage and abnormal antioxidant levels in cyclophosphamide (CP) induced hepatotoxicity. Male Wistar rats of 140± 20 g were categorized into four groups. Two groups were administered CP (15 mg/kg body weight once a week for 10 weeks by oral gavage) to induce hepatotoxicity; one of these groups received lipoic acid treatment (35 mg/kg body weight intraperitoneally once a week for 10 weeks; 24 h prior to the CP administration). A vehicle (saline) treated control group and a lipoic acid drug control group were also included. The extent of liver damage in CP-induced rats was evident from the increased activities of serum aminotransferases, alkaline phosphatase and lactate dehydrogenase; whereas lipoic acid pretreatment prevented the rise in these marker enzymes. We evaluated the changes in activities/levels of tissue enzymic (superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase and glucose-6-phosphate dehydrogenase) and non-enzymic (reduced glutathione, ascorbate and α-tocopherol) antioxidants along with malondialdehyde levels in the experimental groups. In CP-administered rats the antioxidant enzymes showed significantly depressed activities (p < 0.001, p < 0.01) and the antioxidant molecules also showed depleted levels (p < 0.001, p < 0.01), in comparison with the control group. However the extent of lipid peroxidation and the abnormal antioxidant status were normalized in lipoic acid pretreated rats. The present work highlights the efficacy of lipoic acid as a cytoprotectant in CP-induced hepatic oxidative injury.

Cardioprotective effect of pentacyclic triterpene, lupeol and its ester on cyclophosphamide-induced oxidative stress

Cyclophosphamide (CP), an alkylating agent widely used in cancer chemotherapy, causes fatal cardiotoxicity. In the present study, lupeol, a pentacyclic triterpene, isolated from Crataeva nurvala stem bark and its ester, lupeol linoleate were investigated for their possible cardioprotective effects against CP-induced toxicity. Male albino rats of Wistar strain were injected with a single dose of CP (200 mg/kg body weight, ip). In CP-administered rats, activities of lactate dehydrogenase and creatine phosphokinase were elevated in serum with a concomitant decline in their activities in the cardiac tissue. Significant increases (P B < 0.001) in the levels of lipid peroxides and a decrease (P B < 0.001) in the levels of enzymic (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase and glutathione-s-transferase) and nonenzymic (reduced glutathione, vitamin C and vitamin E) antioxidants in the heart were also observed. The cardioprotective effects of lupeol (50 mg/kg body weight for 10 days orally) and its ester, lupeol linoleate (50 mg/kg body weight for 10 days orally) were evident from the significant reversal of the above alterations induced by CP. These observations highlight the antioxidant property of triterpenes and their cytoprotective action against CPinduced cardiotoxicity.

Lupeol and its ester ameliorate the cyclophosphamide provoked cardiac lysosomal damage studied in rat.

Cyclophosphamide (CP), an alkylating agent widely used in cancer chemotherapy causes fatal cardiotoxicity. Lupeol, a pentacyclic triterpene, isolated from Crataeva nurvala stem bark and its ester, lupeol linoleate possess a wide range of medicinal properties. The effect of lupeol and its ester was evaluated in CP-induced myocardial toxicity in rats. Male albino rats of Wistar strain were categorized into six groups. Group I served as control. Rats in groups II, V and VI animals were injected intraperitoneally with a single dose of CP (200 mg/kg body weight) dissolved in saline. CP-treated groups V and VI received lupeol and lupeol linoleate (50 mg/kg body weight), respectively, dissolved in olive oil for 10 days by oral gavage. CP-administered rats showed a significant increase (p < 0.001) in the activities of lysosomal hydrolases in serum and heart, a decrease (p < 0.001) in the levels of cellular thiols and myofibres were swollen with loss of myofilaments in electron microscopical analysis in heart. Lupeol and its ester showed reversal of the above alterations induced by CP. These findings demonstrate that the supplementation with lupeol and its ester could preserve lysosomal integrity, improve thiol levels, highlighting their protective effect against CP-induced cardiotoxicity.

Remedial effect of DL-α-lipoic acid against adriamycin induced testicular lipid peroxidation

Adriamycin (ADR), a cytotoxic antineoplastic drug is used in the treatment of various solid tumors. However, its efficacy continues to be challenged by significant toxicities including testicular toxicity. In the present study, the effect of lipoic acid, a “universal antioxidant” was investigated on ADR induced peroxidative damages in rat testis. Adult male albino rats of Wistar strain were administered ADR (1 mg/kg body weight, i.v.) once a week for 10 weeks. ADR injected rats showed a significant decline in the activities of enzymic antioxidants (catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase) and non-enzymic antioxidants (reduced glutathione, Vitamin A, Vitamin C and Vitamin E) with high malondialdehyde levels. The extent of testicular toxicity was evident from the decreased activities of testicular marker enzymes (sorbitol dehydrogenase and glucose-6-phosphate dehydrogenase). Treatment with lipoic acid (35 mg/kg body weight, i.p.) one day prior to ADR administration, maintained near normal activities of the enzymes and significantly reduced lipid peroxidation, thereby proving it to be an effective cytoprotectant. (Mol Cell Biochem 267: 209–214, 2004)

Lupeol and its ester exhibit protective role against cyclophosphamide-induced cardiac mitochondrial toxicity.

Cyclophosphamide (CP), an anti-cancer and immunosuppressant drug, causes fatal cardiotoxicity during high dose chemotherapy. Lupeol, a pentacyclic triterpene, isolated from Crataeva nurvala stem bark and its ester, lupeol linoleate, possess wide range of medicinal properties. The objective of this study was to establish the pharmacological efficacy of lupeol and its ester against CP-induced mitochondrial-cardiomyopathy. Male albino rats of Wistar strain were injected with a single dose of CP (200 mg/kg body weight, i.p.). A decrease in the activities of TCA cycle enzymes such as succinate dehydrogenase, malate dehydrogenase, and isocitrate dehydrogenase were noted in CP-treated rats. Simultaneously there was a decrease in the activities of mitochondrial complexes of electron transport chain. Electron microscopical observations were also in agreement with the above changes. Mitochondria were swollen with numerous electron dense granules and showed damaged cristae, revealing the cytotoxic effect of CP. Lupeol (50 mg/kg body weight for 10 days orally) and its ester, lupeol linoleate (50 mg/kg body weight for 10 days orally) showed reversal of the above alterations induced by CP. These data suggest that the protective effects of lupeol and its ester against CP-induced cardiac damage were achieved by restoration of mitochondrial structure and function.

Lupeol and its ester inhibit alteration of myocardial permeability in cyclophosphamide administered rats

Cyclophosphamide (CP), an alkylating agent widely used in cancer chemotherapy causes cardiac membrane damage. Lupeol, a pentacyclic triterpene, isolated from Crataeva nurvala stem bark and its ester, lupeol linoleate possess a wide range of medicinal properties. The effect of lupeol and its ester was evaluated in CP induced alterations in cardiac electrolytes in rats. Male albino rats of Wistar strain were categorized into 6 groups. Group I served as control. Rats in groups II, V and VI were injected intraperitoneally with a single dose of CP (200 mg/kg body weight) dissolved in saline. CP treated groups V and VI received lupeol and lupeol linoleate (50 mg/kg body weight) respectively, dissolved in olive oil for 10 days by oral gavage. At the end of the experimental period, urinary risk factors, activities of ATPases and electrolytes were measured using standard procedures. CP administered rats showed a significant decrease (P < 0.001) in the activities of ATPases. It was associated with significant alterations (P < 0.001) of electrolytes both in serum and cardiac tissue. The levels of urea, uric acid and creatinine were also significantly (P < 0.001) altered in the serum and urine. Lupeol and its ester showed reversal of the above alterations induced by CP. These findings demonstrate that the supplementation with lupeol and its ester could preserve membrane permeability, highlighting their protective effect against CP induced cardiotoxicity.