Therapeutic efficacy of DL-alpha-lipoic acid on cyclosporine A induced renal alterations.
The present study was designed to evaluate the possible beneficial effect of lipoic acid in preventing the renal damage induced by cyclosporine A in rats. Male albino rats of Wistar strain were divided into four groups and treated as follows. Two groups received cyclosporine A by oral gavage (25 mg/kg/body weight) for 21 days to induce nephrotoxicity, one of which simultaneously received lipoic acid treatment (20 mg/kg body weight) for 21 days. A vehicle (olive oil) and a lipoic acid drug control were also included. Cyclosporine A induced renal damage was evident from the decreased activities of tissue marker enzymes (alkaline phosphatase, acid phosphatase, lactate dehydrogenase, aspartate transaminase and alanine transaminase) and decreased activities of ATPases (Na+, K+-ATPase, Ca2+-ATPase and Mg2+ ATPase). An apparent increase in the levels of serum constituents (urea, uric acid and creatinine) and urinary marker enzymes (N-acetyl-beta-D-glucosaminidase, beta-glucosidase, beta-galactosidase, cathepsin-D and gamma-glutamyl transpeptidase) along with significant decline in creatinine clearance were seen in the cyclosporine treated rats, which was reversed upon treatment with lipoic acid. Ultrastructural observations were also in agreement with the above abnormal changes. Lipoic acid effectively reverted these abnormal biochemical changes and minimized the morphological lesions in renal tissue. Hence, this study clearly exemplifies that lipoic acid might be an ideal choice against cyclosporine A induced cellular abnormalities.
Amudha
Ganapathy
G
Department of Medical Biochemistry, Dr. ALM. Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai-600 113, India.
Josephine
Anthony
A
Mythili
Yenjerla
Y
Sundarapandiyan
Rajaguru
R
Varalakshmi
Palaninathan
P
D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism / Q000652:urine; D016572:Cyclosporine; D004195:Disease Models, Animal; D004798:Enzymes / Q000378:metabolism / Q000652:urine; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D020011:Protective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D008063:Thioctic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D013997:Time Factors
D015415:Biomarkers; D004798:Enzymes; D020011:Protective Agents; D008063:Thioctic Acid; D016572:Cyclosporine