Protective effect of DL-alpha-lipoic acid on cyclophosphamide induced hyperlipidemic cardiomyopathy.
Cyclophosphamide is a potent alkylating agent used in cancer chemotherapy and immunosuppression. The present study is aimed at evaluating the role of a potent antioxidant lipoic acid in cyclophosphamide induced hyperlipidemic cardiomyopathy. Adult male Wistar rats were divided into four treatment groups. Two groups received single intraperitoneal injection of cyclophosphamide (200 mg/kg body weight) to induce cardiotoxicity, one of these groups received lipoic acid treatment (25 mg/kg body weight, orally for 10 days). A vehicle treated control group and a lipoic acid drug control were also included. Cyclophosphamide administration resulted in abnormal elevation of serum lipids. Similarly in the cardiac tissue, the levels of free cholesterol, esterified cholesterol, triglycerides were increased significantly (P<0.05) while the levels of phospholipids and free fatty acids were reduced significantly unlike serum (P<0.05). Serum Low Density Lipoprotein (LDL) and Very Low Density Lipoprotein (VLDL) cholesterol increased significantly (P<0.05) while High Density Lipoprotein (HDL) cholesterol (P<0.05) decreased significantly when compared to controls. These changes corroborated with the abnormal distortion in the activities of lipid metabolizing enzymes in cyclophosphamide treated group. Supplementation of lipoic acid reverted these abnormalities in the lipid levels and activities of lipid metabolizing enzymes to near normalcy after cyclophosphamide administration.
Mythili
Yenjerla
Y
Department of Medical Biochemistry, Dr. ALM. Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600 113, India.
Sudharsan
Periyasamy Thandavan
PT
Sudhahar
Varatharajan
V
Varalakshmi
Palaninathan
P
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D009202:Cardiomyopathies / Q000097:blood / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D003520:Cyclophosphamide; D006949:Hyperlipidemias / Q000097:blood / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D050356:Lipid Metabolism / Q000187:drug effects*; D008055:Lipids / Q000097:blood; D008071:Lipoprotein Lipase / Q000378:metabolism; D008074:Lipoproteins / Q000097:blood; D008297:Male; D009206:Myocardium / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D002787:Sterol Esterase / Q000378:metabolism; D008063:Thioctic Acid / Q000494:pharmacology* / Q000627:therapeutic use
D000975:Antioxidants; D008055:Lipids; D008074:Lipoproteins; D008063:Thioctic Acid; D003520:Cyclophosphamide; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; C031695:acid cholesterol ester synthetase; D002787:Sterol Esterase; D008071:Lipoprotein Lipase