Abstract
OBJECTIVE: Cisplatin is a highly potent and commonly used antineoplastic agent. However, it has been reported to induce male sexual dysfunction (SD) via the downregulation of testosterone and nitric oxide (NO)/ cyclic guanosine monophosphate (cGMP) signaling. On the other hand, L-arginine upregulates NO/cGMP signaling and may attenuate cisplatin-induced male sexual dysfunction. Thus, the current study examined the effect of L-arginine on cisplatin-induced male SD with a focus on testosterone bioavailability and NO/cGMP as a potential target pathway. METHODS: Twenty-four male Wistar rats were allotted randomly to four groups: control, L-arginine-treated, cisplatin-treated, and cisplatin co-treatment with L-arginine. RESULTS: Cisplatin therapy significantly lowered libido and sexual vigor, evinced by extended mount, intromission, and ejaculation latencies and reduced motivation to mate and mount, intromission, and ejaculation frequencies, as well as penile reflex. Moreover, cisplatin downregulated circulating testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). In addition, cisplatin exposure markedly reduced dopamine and cavernosal levels of NO and cGMP and increased cavernosal acetylcholinesterase, monoamine oxidase, and arginase. Also, cisplatin increased cavernosal malondialdehyde, NF-kB, TNF-α, IL-1β, and IL-6 but reduced GSH, SOD, and catalase. However, co-administration of L-arginine attenuated cisplatin-induced SD by improving the indices of the male sex act and upregulating testosterone, LH, FSH, NO, cGMP, and dopamine. Arginine co-therapy also suppressed cytokine levels and improved penile redox state. CONCLUSIONS: L-arginine attenuates cisplatin-induced male SD by modulating circulating testosterone and NO/cGMP signaling.