OBJECTIVE:Methotrexate (MTX) leads to acute toxic side effects in tissues or organs containing rapidly dividing cells such as seminiferous tubules. In this study, we investigated the protective effects of vitamin C against MTX-induced injury in rat testis.

MATERIAL AND METHODS:A total of 31 rats were divided into 4 groups, including the control group. The study was completed within 4 weeks and the rats received daily doses of 2 mL/kg SF, 100 mg/kg vitamin C and 10 mg/kg/day MTX i.p according to their groups. The mean seminiferous tubular diameter, germinal epithelial cell thickness, and mean testicular biopsy score were determined by histologic examination of each group.

RESULTS:The vitamin C + MTX group showed more similarity with the control group. Statistically significant results were achieved between groups as for mean seminiferous tubular diameter, germinal epithelial cell thickness, and mean testicular biopsy score. When compared with the group which received vitamin C after MTX therapy, values for mean seminiferous tubular diameter, germinal epithelial cell thickness, and mean testicular biopsy score were significantly higher in the group which received vitamin C before initiation of MTX therapy.

CONCLUSION:Vitamin C decreased MTX-induced testicular histological injuries, especially when used before MTX therapy.

Like several other anticancer drugs, methotrexate (MTX) causes side effects, such as neuropathic pain, hepatotoxicity, and nephrotoxicity. Abnormal production of reactive oxygen species has been suspected in the pathophysiology of MTX-induced hepatorenal toxicity. Therefore, the aim of this study was to investigate the probable protective role of vitamin C (Vit C) on oxidative stress induced by MTX in the liver and kidney tissues of rats. A total of 32 rats were randomly and equally divided into four groups. The first group served as the control group. The second group received a single dose of 20 mg/kg of MTX intraperitoneally. To demonstrate our hypothesis, the third and the fourth groups received 250 mg/kg of Vit C for 3 days by oral gavage, with or without MTX treatment. At the end of the study, the liver and kidney tissues of the rats were collected and examined using histology. Boththe tissues were assayed for malondialdehyde concentration and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities. In hepatic and renal tissues, lipid peroxidation levels were increased, whereas SOD, CAT, and GSH-Px levels were decreased by MTX. All parameters, including CAT levels in hepatic tissue, were significantly restored after the administration of Vit C for 3 days. Similar to the biochemical findings, evidence of oxidative damage was examined in both types of tissues by histopathological examination. From the results of this study, we were able to observe that Vit C administration modulates the antioxidant redox system and reduces the renal and hepatic oxidative stress induced by MTX. Vit C can ameliorate the toxic effect of MTX in liver and kidney tissues of rat.