Melatonin prevents cyclosporine-induced nephrotoxicity in isolated and perfused rat kidney.
Cyclosporine A (CsA) is a potent and effective immunosuppressive agent, but its action is frequently accompanied by severe renal toxicity. The precise mechanism by which CsA causes renal injury is not known. Reactive oxygen species (ROS) have been shown to play a role, since CsA-induced renal lipid peroxidation is attenuated in vivo and in vitro by the concomitant administration of antioxidants such as vitamin E. We show here the effect of the antioxidant melatonin (MLT), a hormone produced by the pineal gland during the dark phase of the circadian cycle, in a model of CsA nephrotoxicity in the isolated and perfused rat kidney. Kidneys isolated from rats were divided into seven groups. At the end of perfusion, malondialdehyde and 4-hydroxyalkenals (MDA + 4-HDA), metabolites of nitric oxide NO2- + NO3- were measured and histopathological examination was performed. CsA treatment induced a significant increase in MDA + 4-HDA while not affecting the nitric oxide metabolite level. MLT remarkably prevented glomerular collapse and tubular damage as revealed by morphometric analysis. Our study suggests that lipid peroxidation is an early important event in the pathogenesis of CsA nephrotoxicity and that MLT is able to protect kidneys from CsA at a relatively low concentration.
Longoni
Biancamaria
B
Department of Oncology, Transplants and Advanced Technologies in Medicine, University of Pisa, Italy.
Migliori
Massimiliano
M
Ferretti
Agnese
A
Origlia
Nicola
N
Panichi
Vincenzo
V
Boggi
Ugo
U
Filippi
Cristina
C
Cuttano
Maria Giuseppa
MG
Giovannini
Luca
L
Mosca
Franco
F
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D016572:Cyclosporine / Q000633:toxicity*; D005919:Glomerular Filtration Rate; D007166:Immunosuppressive Agents / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects*; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008550:Melatonin / Q000627:therapeutic use*; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar
D000975:Antioxidants; D007166:Immunosuppressive Agents; D009566:Nitrates; D009573:Nitrites; D008315:Malondialdehyde; D016572:Cyclosporine; D008550:Melatonin