Molecular insights into the protective role of nano-naringin in mancozeb-induced testicular damage and infertility.

Mancozeb (MZ) is an extensively used fungicide with well-documented reproductive toxicity induced by oxidative stress and hormonal disruption. Antioxidants such as naringin (NAR) have been studied as protective agents, but their therapeutic application is limited by poor bioavailability. Nano-formulated approaches, including chitosan-coated nanoparticles (NARNPs), offer a promising strategy to enhance delivery and efficacy. The present study explores this concept by evaluating the protective effects of NAR and NARNPs against MZ-induced testicular damage and infertility in rats. 42 adult male albino Wistar rats were divided into six groups (n = 7) as follows: (1) control, (2) NAR (20 mg/kg bwt), (3) NARNPs (20 mg/kg bwt), (4) MZ (250 mg/kg bwt), (5) NAR + MZ, and (6) NARNPs + MZ. Data revealed that the exposure of rats to MZ caused a significant decrease in the body weight gain, sperm viability and motility, serum testosterone level, and testicular antioxidant enzyme activities, along with an increase in the lipid peroxidation. MZ also inhibited the expression of steroidogenic genes and proliferating markers in testes. The administration of NAR with MZ partially restored oxidative homeostasis and the reproductive biomarkers. Otherwise, NARNPs were more effective than NAR, which substantially improved the testicular morphology and function, as well as partially returned the gene expression back to normal with higher immunoexpression of proliferating markers in testicular tissues. The study highlights the potential of nano-formulated NAR as a promising strategy to counteract MZ-induced reproductive damage and improve testicular health via enhancing steroidogenic gene expression.