Protective Effects of p-Coumaric Acid Against Paclitaxel-Induced Testicular Damage: Role of Oxidative Stress, Inflammation, Apoptosis, and Autophagy.

Paclitaxel (PTX), despite its widespread antineoplastic use, induces severe reproductive toxicity by triggering oxidative stress, inflammation, and apoptosis in testicular tissue. In this study, the effects of p-Coumaric Acid (PCA) on oxidative stress, inflammation, apoptosis, and hormonal balance were evaluated at histopathological, biochemical, and molecular levels in a rat model of PTX-induced testicular injury. PTX increases reactive oxygen species (ROS) production and suppresses antioxidant defenses, thereby elevating lipid peroxidation; enhances nuclear factor kappa-B (NF-κB) and Toll-like receptor 4 (TLR4)-mediated pro-inflammatory cytokines interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α); and reduces interleukin-10 (IL-10) levels. The accompanying increase in Bcl-2-associated X protein (Bax) and Caspase-3, along with a decrease in B-cell lymphoma-2 (Bcl-2), leads to germ cell loss and impaired spermatogenesis. In our study, PCA markedly attenuated these PTX-induced oxidative, inflammatory, and apoptotic processes. PCA treatment reduced malondialdehyde (MDA) levels, enhanced superoxide dismutase (SOD) and glutathione (GSH) activities, normalized cytokine balance, and preserved seminiferous tubule integrity. Moreover, PCA improved sperm density and motility, decreased abnormal morphology, and partially restored reduced testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels. Overall, the findings indicate that PCA may serve as a potential therapeutic agent against PTX-induced testicular damage through its strong antioxidant and cytoprotective effects.