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<0.001) in the levels of lipid peroxides and a decrease (P<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 CP-induced cardiotoxicity.
Sudharsan
P T
PT
Department of Medical Biochemistry, Dr. ALM. Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, India.
Mythili
Y
Y
Selvakumar
E
E
Varalakshmi
P
P
D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology; D031483:Capparaceae / Q000737:chemistry; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D003402:Creatine Kinase / Q000097:blood; D003520:Cyclophosphamide / Q000633:toxicity*; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D004952:Esters; D005978:Glutathione / Q000378:metabolism; D006576:Heterocyclic Compounds, 4 or More Rings / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007770:L-Lactate Dehydrogenase / Q000097:blood; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009153:Mutagens / Q000633:toxicity; D009206:Myocardium / Q000201:enzymology; D018384:Oxidative Stress / Q000187:drug effects*; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D014315:Triterpenes / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D008041:Linoleic Acids; D000094042:Lupanes
D000975:Antioxidants; D002316:Cardiotonic Agents; D002374:Catalase; D003402:Creatine Kinase; D003520:Cyclophosphamide; D004952:Esters; D005978:Glutathione; D006576:Heterocyclic Compounds, 4 or More Rings; D007770:L-Lactate Dehydrogenase; D009153:Mutagens; D010936:Plant Extracts; D013482:Superoxide Dismutase; D014315:Triterpenes; C403497:lupeol linoleate; D008041:Linoleic Acids; D000094042:Lupanes