Diallyl Disulfide Prevents Cisplatin-Induced Testicular Injury by Regulating NADPH-Oxidase, NF-κB, and Necroptosis Signals

Cisplatin (CDDP), a frequently used chemotherapeutic drug, has been linked to testicular toxicity, which may impact reproductive health. This study examined diallyl disulfide (DADS), a garlic organosulfur compound, protecting against CDDP-induced testicular damage. In this examination, rats were assigned to control, DADS (10 mg/kg), CDDP (10 mg/kg), and DADS + CDDP groups. The administration of DADS restored testosterone, LH, and FSH levels, minimizing the endocrine disruption produced by CDDP. Biochemical analyses demonstrated considerable attenuation of oxidative stress, evidenced by reduced MDA content and an increase in GSH and SOD activity evoked by NADPH-oxidase downregulation. DADS mitigated inflammation by downregulating NF-κB and iNOS signaling, thereby lowering TNF-α and IL-1β levels. Moreover, DADS dampened necroptosis by lowering MLKL, RIP1, and RIP3 expression. These data indicate that DADS substantially reduces CDDP testicular injury by suppressing oxidative injury, inflammation, and necroptosis, underlining its potential as an adjuvant therapeutic drug in chemotherapy.