Lupeol and Its Ester Exhibit Protective Role Against Cyclophosphamide-Induced Cardiac Mitochondrial Toxicity

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Abstract
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.