title: Effect of DL-alpha-lipoic acid on cyclophosphamide induced lysosomal changes in oxidative cardiotoxicity.
abstract: Cyclophosphamide (CP), one of the widely prescribed antineoplastic drugs can cause fatal cardiotoxicity. The present study is aimed at evaluating the cardioprotective role of lipoic acid in CP induced toxicity. Male albino rats of Wistar strain were divided into four groups and treated as follows: Group I served as control, Group II received a single dose of CP (200 mg/kg b.wt., i.p.), Group III received lipoic acid (25 mg/kg b.wt., orally) for 10 days, and Group IV received CP immediately followed by lipoic acid for 10 days. In CP administered rats, the levels of protein carbonyl and 8-hydroxy-2-deoxyguanosine were increased significantly (P<0.001) indicating oxidative changes in the heart tissue. The activities of lysosomal acid hydrolases, beta-Glu, beta-Gal, NAG, Cat-D and ACP increased significantly (P<0.001) in the serum as well as in the heart tissue after CP administration. An increase in hydroxyproline was observed in CP induced rats. Lipoic acid effectively reverted these abnormal biochemical changes to near normalcy. These observations highlight the protective role of lipoic acid in CP induced cardiotoxicity.
authors.affiliation: Department of Medical Biochemistry, Dr. ALM. Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai - 600 113, India.
authors.forename: Y
authors.initials: Y
authors.lastname: Mythili
authors.forename: P T
authors.initials: PT
authors.lastname: Sudharsan
authors.forename: G
authors.initials: G
authors.lastname: Amudha
authors.forename: P
authors.initials: P
authors.lastname: Varalakshmi
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000704:Analysis of Variance; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000633:toxicity*; D002851:Chromatography, High Pressure Liquid; D003520:Cyclophosphamide / Q000633:toxicity*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D006909:Hydroxyproline / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D020011:Protective Agents / Q000494:pharmacology*; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D008063:Thioctic Acid / Q000494:pharmacology*
chemical_list: D018906:Antineoplastic Agents, Alkylating; D020011:Protective Agents; D008063:Thioctic Acid; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003520:Cyclophosphamide; D003849:Deoxyguanosine; D006909:Hydroxyproline