Empagliflozin and naringenin mitigate cisplatin-induced testicular injury via modulating NLRP3 inflammasome-mediated pyroptosis: Integrated molecular docking and in vivo evidence
Abstract
BACKGROUND: Cisplatin (CP) is a potent anticancer drug; however, its medical use is constrained by multiple organ toxicity. CP-induced testicular injury is mainly driven by oxidative stress and inflammation.
AIM: The current study scrutinizes and compares the efficacy of colchicine (Col), empagliflozin (Empa), and naringenin (Nar) on CP-induced testicular toxicity in rats, emphasizing their possible inhibitory effect on NF-κB/inflammasome pathway.
METHODS: The study integrated molecular docking with in vivo experiments. Docking evaluated interactions of Col, Empa, and Nar with NLRP3. Male rats administered Empa or Nar (10 or 50 mg/kg/day, respectively) orally for 6 weeks followed by a single dose of CP (7 mg/kg, i.p.). Col was administered for one week prior to CP injection, then all treatments were continued for one more week prior to termination.
RESULTS: Empa and Nar significantly restored testicular oxidative stress, hormonal profile and sperm quality and preserving histopathological architecture. The protective effects correlated with diminished inflammation and pyroptosis, as evidenced by suppressed CP-induced up-regulation of testicular NF-κB, NLRP3, cleaved caspase-1, IL-1β, IL-18, and GSDMD-N.
CONCLUSION: Empa and Nar mitigate against CP-induced reproductive toxicity by reducing oxidative stress, inflammation, and pyroptosis, thereby offering potential to enhance the safety of CP chemotherapy regimens.
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