l-arginine mitigates endocrine and spermatogenesis disruptions in cisplatin-exposed male Wistar rats by modulating iNOS/NO/NF-kB and Nrf2/HO-1 signaling.

BACKGROUND

Even though cisplatin is highly effective in cancer treatment, its toxicity to non-target organs, such as the testes, remains a concern. Studies have shown that cisplatin induces testicular toxicity by activating an oxido-inflammatory response. Conversely, arginine exerts antioxidant and anti-inflammatory properties.

AIM: Hence, the current study assessed the impact of arginine on cisplatin-induced testicular toxicity. In addition, the involvements of iNOS/NO/NF-kB and Nrf2/HO-1 signaling, which are key pathways in cisplatin toxicity, were probed.

MATERIALS AND

METHODS

Twenty-four male Wistar rats were acclimatized for two weeks and then randomized into 4 equal groups; control, arginine-treated, cisplatin-treated, and cisplatin + arginine-treated.

RESULTS

Arginine significantly attenuated cisplatin-induced reductions in sperm concentration, motility, and viability and increased the percentage of abnormal sperm morphology. More so, arginine markedly suppressed cisplatin-induced reductions in daily and total spermatid production, and circulating levels of GnRH, FSH, LH, and testosterone. Additionally, arginine improved cisplatin-induced distortion in testicular histology. These findings were associated with arginine-driven mitigation of cisplatin-induced rise in MDA, TNF-α, IL-6, IL-1β, iNOS, and NF-kB and cisplatin-induced decline in GSH, TAC, IL-10, NO, and Nrf2 levels and GR, SOD, catalase, and HO-1 activities.

CONCLUSION

Summing up, arginine mitigated cisplatin-induced testicular endocrine and spermatogenesis disruption via the modulation of iNOS/NO/NF-kB and Nrf2/HO-1 signaling.