Chemoprotective effect of melatonin against cisplatin‐induced testicular toxicity in rats

Abstract

In this study, we investigated the effect of melatonin on cisplatin-induced spermiotoxicity using quantitative, biochemical and histopathological approaches. Cisplatin (CP, 7 mg/kg) and melatonin (10 mg/kg) were intraperitoneally injected. The rats were decapitated on 5th (short-term group) or 50th day (long-term group) after CP injection. Traits of reproductive organs, sperm characteristics, testicular histological findings, and the lipid peroxidation in the testicular tissue were determined. Melatonin mitigated CP-induced reductions in testes, epididymis and accessory gland weights in rats decapitated on day 5. Both short- and long-term CP treatment decreased sperm concentration, sperm motility and increased abnormal sperm rates compared with the control. But the reduction of sperm concentration in long-term CP treatment was insignificant. Although treatment with melatonin provided moderately normalization with respect to sperm concentration in short-term treatment group, melatonin caused a marked normalization of sperm motility in both CP + melatonin groups. Both groups treated with the melatonin showed decreases in abnormal sperm rates compared with alone CP. While testicular malondialdehyde levels were elevated after CP treatment, glutathione peroxidase activity decreased significantly in both groups. Glutathione levels reduced after long-term treatment, but not in short-term group by CP administration. Treatment with CP plus melatonin provided significant amelioration of oxidative stress parameters. Histopathological findings of testes in both short- and long-term treatment groups paralleled the biochemical and spermatogenic results. This study clearly indicates that CP-treatment impaired markedly testicular function and combined treatment with melatonin prevented much of the toxicity in rats.

Ascorbic Acid (Vitamin C)-Mediated Protection on Mutagenic Potentials of Cisplatin in Mice Bearing Ascites Dalton ’s Lymphoma

“…It has also been reported that co-administration of speman with cisplatin showed significant improvement on the sperm quantity and quality along with enhanced steroidogenesis in mice (Sainath et al, 2011). In fact the use of another antioxidant, i.e., melatonin in combination with cisplatin has also shown chemoprotective effect against cisplatin-induced testicular toxicity in rats (Atessahin et al, 2006) which also supports the present findings.…”

“…Anticancer drugs/chemicals induce sperm abnormalities indicating its genotoxicity to germ cells (Wyrobek et al, 1983;Seetharama Rao and Narayana, 2005;Atessahin et al, 2006). Cisplatin has been considered as a potent mutagen causing formation of abnormal male germ cells (Sawhney et al, 2005;Mohammadnejad et al, 2012).…”

Beneficial Effects of Montelukast against Cisplatin-Induced Acute Renal Damage in Rats

“…17,[26][27][28] One of its most frequent and serious side effects is nephrotoxicity, which is described as acute tubular necrosis (ATN). Although the mechanisms of CP-induced nephrotoxicity are not fully understood, one mechanism of this toxicity is believed to involve ROS generation and inflammatory machine in the pathophysiology of CP-induced ATN after even a single dose of the drug.…”

Antioxidant Systems and Oxidative Stress in the Testes

“…This evolutionarily conserved compound has been shown to reduce oxidative stress in the testes induced by ethanol, 167 indomethacin, 168 X-irradiation, 169 streptozotocin-induced diabetes, 86 and cisplatin. 136 In vitro studies have also shown that melatonin and its immediate precursor N-acetyl-serotonin could inhibit ascorbate-Fe (II) induced lipid peroxidation in rat testicular microsomes and mitochondria. 170,171 The administration of antioxidants such as resveratrol, ascorbate or cocoa rich in flavanols to normal animals, not suffering from induced oxidative stress, also appears to improve testicular function, suggesting that oxidative stress is a consistent feature of testicular physiology.…”