Melatonin: an antioxidant protects against cyclosporine-induced nephrotoxicity

Transplantation. 1999 Apr 15;67(7):1065-8. doi: 10.1097/00007890-199904150-00022.

Abstract

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.

Conclusion: These results indicate that Mel, through its antioxidant properties, provides protection against CsA-induced nephrotoxicity.

MeSH terms

  • Animals
  • Antioxidants / therapeutic use*
  • Calcinosis / chemically induced
  • Calcinosis / pathology
  • Calcinosis / prevention & control
  • Creatinine / blood
  • Creatinine / pharmacokinetics
  • Cyclosporine / adverse effects*
  • Kidney Diseases / chemically induced*
  • Kidney Diseases / pathology
  • Kidney Diseases / prevention & control*
  • Lithium / pharmacokinetics
  • Male
  • Malondialdehyde / blood
  • Melatonin / therapeutic use*
  • Nephrons / drug effects*
  • Rats
  • Rats, Wistar
  • Urea / blood

Substances

  • Antioxidants
  • Malondialdehyde
  • Cyclosporine
  • Urea
  • Lithium
  • Creatinine
  • Melatonin