Background: Chemotherapeutics, one of the standard treatment options for cancer worldwide, have various adverse effects, including erectile dysfunction (ED). Aim: To investigate erectile function in an animal model after administration of the anticancer agent oxaliplatin (L-OHP). Methods: Male Wistar/ST rats were divided into 2 groups: L-OHP rats (n = 21), which were intravenously administered L-OHP (4 mg/kg; twice a week for 4 weeks), and Control rats (n = 21), which were injected with the same volume of 5% glucose solution, using the same dosing schedule. At the end of the study period, erectile function was evaluated by measuring intracavernous pressure (ICP) and mean arterial pressure (MAP) after cavernous nerve stimulation (n = 9−10). Endothelial function was evaluated with an isometric tension study using corpus cavernosum strips (n = 11). Western blot analysis was used to assess neuronal nitric oxide (nNOS) and endothelial NO synthase (eNOS) protein levels (n = 7). Real-time quantitative polymerase chain reaction (qRT-PCR) was used to assess the expression of inflammation-and oxidative stress-related markers (nicotinamide adenine dinucleotide phosphate oxidase-1, p22 phox , interleukin [IL]-6, and nuclear factor-kappa B) (n = 6). Statistical significance was determined using the Student's t-test. Outcomes: The L-OHP group had a significantly lower ICP:MAP ratio than the control group (P < .05). Compared to the Control group, the L-OHP group exhibited significantly lower responses to ACh and eNOS protein levels and significantly higher inflammatory biomarker levels. Clinical Translation: The results based on this animal model indicate that use of the anticancer agent L-OHP should be considered as a risk factor for ED occurring via reduction of NO bioavailability in humans; our results provide possible treatment strategies for maintaining the erectile function of cancer survivors. Strengths and limitations: Our study showed that the anticancer agent L-OHP has the propensity to cause ED in rats. A major limitation of this study is the lack of an established cure for ED associated with L-OHP and the lack of clinical evidence. Conclusions: L-OHP causes ED in rats via reduction of NO bioavailability caused by endothelial dysfunction.

Background: A platinum-containing anti-cancer agent, oxaliplatin (L-OHP), is known to induce peripheral neuropathy, including erectile dysfunction (ED) as a side effect, while Gosha-jinki-gan (GJG) is a traditional Japanese herbal medicine mainly used for peripheral neuropathy. Aim: To investigate the effect of GJG on L-OHP-induced ED in rats. Methods: Twelve-week-old male Wister/ST rats were categorized into the following groups: Sham, Sham+GJG, L-OHP, and L-OHP+GJG (each n = 10). The L-OHP and L-OHP+GJG groups were injected intravenously with L-OHP (4 mg/ kg) for 2 consecutive days in the first week. Statistical significance was determined using Bonferroni's multiple comparison test. Outcomes: At the end of the study period, erectile function was evaluated by measuring intracavernosal pressure (ICP) and mean arterial pressure (MAP) after cavernous nerve stimulation. Western blot analysis was used to assess the neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS) levels, and quantitative polymerase chain reaction was used to assess the expression of phosphodiesterase-5 (PDE-5) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-1. Results: The ICP/MAP ratio of L-OHP rats (0.34 § 0.06) was significantly lower than that of Sham rats (0.67 § 0.03, P < .01), however, the ICP/MAP ratio of L-OHP+GJG rats (0.55 § 0.01) was significantly higher than that of L-OHP rats (P < .01). There were no significant differences in the nNOS and eNOS protein expression between both groups (P > .05). GJG administration significantly decreased PDE-5 and NADPH oxidase-1 messenger RNA expressions in the L-OHP+GJG group. Clinical Translation: This animal model study suggests that GJG might be effective for erectile function in cancer survivors.Strengths & limitations: Our study identified that GJG had no notable side effects in the treated group. Further investigation of the cavernous nerve would also help elucidate the mechanism of GJG effect, which is a limitation of this study. Conclusion: We found that GJG administration improved L-OHP-induced ED by improving transcriptional

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.