RESUMO
Cisplatin [CDDP] is a widely used chemotherapeutic agent. However, it results in severe oto and nephro-toxicity. Sodium thiosulphate [STS] and melatonin were suggested to protect against CDDP-induced toxicity. This study was carried out to evaluate the effect of both agents on this toxicity. Seventy adult albino rats were comprised in this work they were classified into seven groups each involved ten rats. The first group received nothing [negative control]. The second, third and fourth groups received intraperitoneally one milliliter distilled water [positive control], STS [800 mg/kg/day] and melatonin [5 mg/ kg/day], respectively. The fifth group received CDDP [5 mg/kg/week] alone, sixth group concurrently received CDDP and STS and the seventh group is co-treated with CDDP and melatonin. After 6 weeks for all rats glutathione [GSH], glutathione reductase [GR], catalase [CAT], supperoxide dismutase [SOD], malondialdehyde [MDA] as an index of lipid peroxidation, blood urea and serum creatinine were determined spectrophotometrically. Also, histopathological examination of the cochlea of the inner ear and renal tissue was carried out. The results revealed that CDDP induced elevation of urea, creatinine and MDA, and decreased GSH and antioxidant enzymes. These biochemical changes were associated with severe damage in cochleas and renal tubules. No significant changes were found with STS and melatonin when received alone. With the use of STS and melatonin with CDDP the biochemical changes were significantly improved as compared to CDDP group. Although no significant difference was found between CDDP/STS and CDDP/melatonin groups, the changes were normalized in CDDP/STS group, but still a significant difference was present between CDDP/melatonin group compared to control group indicating that STS has protective effect better than melatonin. These results were associated with improved histopathological changes of the cochlea and kidney. In conclusion CDDP-induced oto- and nephro-toxicity that may be related to increased lipid peroxidation associated with reduced level of GSH and activity of antioxidant enzymes. Also, this study revealed that STS is superior for melatonin, in short term protection against CDDP-induced toxicity and prevention of lipid peroxidation and oxidative stress and in improving antioxidant status. It is recommended to use both thiol agents and melatonin during treatment of human cancer to ameliorate the oxidative stress produced by the drug. However, further studies are required to evaluate the impact of these agents on antitumoral efficacy of CDDP