Naringenin mitigates aflatoxin B1-induced male reproductive toxicity in rabbits through immune and antioxidant remodeling associated with alterations in the IL-27/NLRP3 inflammasome axis.

Naringenin (NAR), a citrus-derived flavanone, is a bioactive compound widely recognized for its potent antidiabetic, anti-inflammatory, and antioxidant properties. However, a significant gap remains in understanding its therapeutic potential against Aflatoxin B1 (AFB1)-induced male reproductive dysfunction. This study investigated the mitigating role of NAR against AFB1-induced reproductive toxicity in rabbit bucks, focusing on redox imbalance, the IL-27/NLRP3 Inflammasome axis, and pyroptosis pathways. Thirty-six mature male rabbits were randomly assigned to four equal groups (n = 9 per group) for two months: control (basal diet), AFB1 (0.3 mg/kg diet), NAR (100 mg/kg diet), and AFB1+NAR (0.3 mg AFB1 + 100 mg NAR/kg diet). Results showed that AFB1 significantly impaired systemic metabolic function, characterized by reduced renal efficiency, elevated hepatic enzymes, increased lipid accumulation, and a marked decline in serum protein concentrations (P < 0.05). Furthermore, AFB1 exposure led to significant deterioration in semen quality, diminished immunological and antioxidant biomarkers, and reduced testosterone levels (P < 0.05). At the cellular level, AFB1 toxicity triggered DNA damage, oxidative stress, adipokine dysregulation, and pyroptosis. Supplementing the diets of AFB1-challenged bucks with NAR substantially restored systemic metabolic function, as evidenced by improved hepatic and renal parameters and modulated lipid profiles (P < 0.01). Furthermore, NAR supplementation mitigated testicular damage, enhanced immunological biomarkers, and suppressed both oxidative stress and inflammation, ultimately rescuing semen quality. Notably, the protective effect may be associated with modulation of the IL-27/NLRP3 pathway. These findings suggest that the IL-27/NLRP3 inflammasome pathway serves as a crucial protective mechanism against AFB1-induced inflammation and pyroptosis. Ultimately, this study demonstrates that dietary NAR effectively mitigates AFB1-induced reproductive dysfunction in rabbits, highlighting its potential as a therapeutic agent for preserving reproductive health.