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L-arginine attenuates cisplatin-induced sexual dysfunction in male Wistar rats by modulating circulating testosterone
O O Obembe1, A A Oladipo2,3, O Ajao4
1Department of Physiology, Osun State University, Osogbo, Osun State, Nigeria.
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.
Insights
L-arginine supplementation can counteract cisplatin-induced male sexual dysfunction by restoring testosterone levels and enhancing nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling pathways. This study demonstrates a potential therapeutic strategy for managing chemotherapy-related side effects.
Area of Science:
- Reproductive Endocrinology
- Pharmacology
- Urology
Background:
- Cisplatin is a vital chemotherapy drug but can cause male sexual dysfunction (SD) by reducing testosterone and nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling.
- L-arginine, a precursor to NO, may mitigate these adverse effects.
Purpose of the Study:
- To investigate the efficacy of L-arginine in attenuating cisplatin-induced male SD.
- To explore the underlying mechanisms involving testosterone bioavailability and the NO/cGMP pathway.
Main Methods:
- Twenty-four male Wistar rats were randomly assigned to four groups: control, L-arginine, cisplatin, and cisplatin with L-arginine.
- Evaluated sexual behavior, hormone levels (testosterone, LH, FSH), penile tissue parameters (NO, cGMP, oxidative stress markers, enzymes), and inflammatory markers.
Main Results:
- Cisplatin significantly impaired sexual behavior, reduced testosterone, LH, and FSH levels, and altered penile NO/cGMP signaling and redox balance.
- L-arginine co-treatment reversed these cisplatin-induced deficits, improving sexual function, restoring hormone levels, and enhancing penile NO/cGMP pathways and antioxidant status.
Conclusions:
- L-arginine effectively attenuates cisplatin-induced male sexual dysfunction.
- The protective effects are mediated through the modulation of circulating testosterone and the enhancement of penile NO/cGMP signaling pathways.
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