Role of lipoic acid in reducing the oxidative stress induced by cyclosporine A.
BACKGROUND
Cyclosporine A (CsA) is the first choice immunosuppressant universally used for the prevention of allograft rejection in solid organ transplantation and immune-mediated diseases. However, with increasing use, evidence has accumulated that CsA therapy is associated with a variety of side effects, the most important being nephrotoxicity. We investigated the potential role of DL-alpha lipoic acid (LA), a universal antioxidant in combating the oxidative stress induced by CsA.


METHODS
Adult male albino Wistar rats were divided into 4 treatment groups. Two groups received CsA (25 mg/kg body weight, orally for 21 days) to induce nephrotoxicity. One of these groups received LA treatment (20 mg/kg body weight, orally) for 21 days concurrently during CsA administration. A vehicle treated control group and a LA drug control were also included.


RESULTS
CsA-induced nephrotoxicity was assessed in terms of increased activities of serum marker enzymes; alkaline phosphatase, acid phosphatase and lactate dehydrogenase. An apparent rise in the activities of N-acetyl-beta-D-glucosaminidase, beta-glucuronidase and cathepsin D were seen in the renal tissue of CsA given rats, which were reversed upon treatment with LA. CsA administration induced significant elevation in lipid peroxidation along with abnormal levels of enzymic (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase and glucose-6-phosphate dehydrogenase) and non-enzymic antioxidants (glutathione, vitamins C and E) in the rat kidney. LA administration improved renal function, by bringing about a significant decrease in peroxidative levels and increase in antioxidant status.


CONCLUSIONS
These results indicate that LA has a protective action against CsA nephrotoxicity and suggest that the LA may find clinical application against a variety of toxins where cellular damage is a consequence of reactive oxygen species.
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
Varalakshmi
Palaninathan
P
D000818:Animals; D016572:Cyclosporine / Q000009:adverse effects*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D008063:Thioctic Acid / Q000494:pharmacology*
D008063:Thioctic Acid; D016572:Cyclosporine