Melatonin: an antioxidant protects against cyclosporine-induced nephrotoxicity.
BACKGROUND
Cyclosporine (CsA) causes a dose-related decrease in renal function in experimental animals. Different mediators for CsA nephrotoxicity have been suggested; oxygen free radicals are one of them. In experimental model of Wistar rats, the role of antioxidant melatonin (Mel), the main product of pineal secretion, was investigated in CsA nephrotoxicity.


METHODS
Male Wistar rats were divided into four groups: saline control, 50 mg/kg CsA, 500 microg/kg Mel, and CsA + Mel. At the end of 14th day of treatment, blood urea, creatinine, malondialdehyde, and creatinine and lithium clearance were estimated. Histopathological examination of kidney from all the groups was performed.


RESULTS
CsA caused marked elevation in blood urea, serum creatinine, and plasma malondialdehyde and a decrease in creatinine and lithium clearance. Mel significantly antagonized CsA-induced renal impairment. Microcalcification in corticomedullary junction seen with CsA was prevented by Mel.


CONCLUSIONS
These results indicate that Mel, through its antioxidant properties, provides protection against CsA-induced nephrotoxicity.
Kumar
K V
KV
Department of Clinical Pharmacology and Therapeutics, Nizam's Institute of Medical Sciences, Hyderabad, India.
Naidu
M U
MU
Shifow
A A
AA
Prayag
A
A
Ratnakar
K S
KS
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D002114:Calcinosis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D003404:Creatinine / Q000097:blood / Q000493:pharmacokinetics; D016572:Cyclosporine / Q000009:adverse effects*; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D008094:Lithium / Q000493:pharmacokinetics; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008550:Melatonin / Q000627:therapeutic use*; D009399:Nephrons / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D014508:Urea / Q000097:blood
D000975:Antioxidants; D008315:Malondialdehyde; D016572:Cyclosporine; D014508:Urea; D008094:Lithium; D003404:Creatinine; D008550:Melatonin