オキサリプラチンは神経障害と内皮障害を介してラットの勃起機能を低下させる

Abstract

Many cancer patients worldwide are treated with chemotherapeutics that cause various side effects, including erectile dysfunction (ED). We investigated the erectile function after the administration of the anti-cancer agent oxaliplatin (L-OHP), by using an animal model. Methods: Twelve-week-old male Wistar-ST rats were stratified into control and L-OHP groups. Rats were administered L-OHP (4 mg/kg i.v. 2 times/week for 4 weeks) in L-OHP group. Erectile and endothelial functions were measured using intracavernosal pressure (ICP) and isometric tension, respectively, after 4 weeks of L-OHP administration. Western blot analysis was used to assess the expression of neuronal nitric oxide (nNOS) and endothelial NO synthase (eNOS). Quantitative PCR was used to assess the expression of inflammation and oxidative stress markers (NADPH oxidase-1, p22phox, IL-6, and NF-κB). Results:The ICP/MAP ratio was significantly lower in the L-OHP group (P < 0.05). L-OHP group exhibited significantly lower responses to ACh, and nNOS and eNOS protein expressions and levels of inflammatory biomarkers were significantly higher in L-OHP group. Conclusion: L-OHP would cause ED through NO bioavailability reduction caused by not only neuronal dysfunction but also endothelial dysfunction. Therefore, cancer survivors who are administered L-OHP should be carefully screened for ED.