Cisplatin [cis-diaminedichloroplatinum(II), CDDP] is a widely used
antineoplastic drug. However, it has major side-effects such as acute tubular
necrosis (ATN). There are a number of studies concerning the role of reactive
oxygen radical species in the pathophysiology of CDDP-dependent ATN. Several
antioxidant agents have been reported to prevent this side-effect but there is no study regarding the protective action of either physiological or pharmacological concentrations of
melatonin.
Melatonin, the chief secretory product of the pineal gland, is a direct
free radical scavenger and indirect
antioxidant. We investigated the effects of
melatonin on CDDP-induced changes of renal
malondialdehyde (MDA), a lipid peroxidation product, and blood
urea nitrogen (BUN) and serum
creatine (Cr). The morphological changes in kidney were also examined using light microscopy. The rats were divided into two groups: pinealectomized (Px) and
sham-operated (non-Px). Both CDDP and
melatonin were administered to all groups. MDA levels were found to be higher in Px than non-Px animals. CDDP administration to Px or non-Px rats increased renal MDA levels and
melatonin administration either before or after CDDP injection caused significant decreases in MDA in kidney compared with those in rats treated with CDDP alone. Serum levels of BUN and Cr did not change as a result of any treatment. Morphological tubule damage because of CDDP was more severe in the renal cortex than in the medulla. The damage to the kidney induced by CDDP was reversed by
melatonin. The results show that pharmacological and physiological concentrations of
melatonin reduce CDDP-induced renal injury.