Hesperidin attenuates gentamicin-induced testicular toxicity via modulation of the PI3K/AKT signaling pathway.

Abstract

Background: Gentamicin is an aminoglycoside antibiotic widely used in the treatment of Gram-negative infections; however, one of its major limitations is testicular toxicity. Oxidative stress is considered to play a central role in gentamicin-induced testicular damage. Hesperidin is a natural flavonoid with potent antioxidant and cytoprotective properties and may exert protective effects on the reproductive system.

Methods: This study investigated the protective effects of hesperidin against gentamicin-induced testicular damage. Histopathological and immunohistochemical evaluations were performed alongside biochemical and hormonal analyses. In addition, sperm concentration, motility, and the rate of abnormal spermatozoa were assessed. To elucidate the underlying molecular mechanisms, the gene expression levels of PD-1, PI3K, and AKT-1 were analyzed.

Results: Gentamicin administration was associated with lower Johnsen scores, decreased testosterone levels and sperm motility, increased sperm abnormalities, elevated MDA concentrations, reduced CAT, SOD, GPx, and GSH levels, increased Caspase-3 and 8-OHdG immunoreactivity, and reduced AKT expression. Hesperidin co-administration significantly attenuated many of these alterations, being associated with improved histopathological scores, enhanced antioxidant status, reduced immunoreactivity of oxidative stress- and apoptosis-related markers, improved sperm quality parameters, and increased PI3K and AKT gene expression compared with the gentamicin-treated group.

Conclusion: These findings indicate that hesperidin possesses a protective potential against gentamicin-induced testicular damage, likely mediated through its antioxidant and anti-apoptotic effects.