Caffeic acid as a protective agent against cisplatin-induced testicular injury: histological, sperm, and molecular evidence

This study investigated the protective efficacy of caffeic acid in reinforcing testicular antioxidant defenses and attenuating cisplatin‑induced oxidative injury. Twenty‑four adult male Balb/c mice were randomly assigned to four experimental groups: control, cisplatin, cisplatin plus caffeic acid, and caffeic acid alone. Cisplatin (2.5 mg/kg, IP) was administered in two cycles of five consecutive days beginning on days 7 and 14, whereas caffeic acid (60 mg/kg, IP) was delivered throughout the 35‑day experimental period. Comprehensive evaluations included histopathological analysis (H&E staining), assessment of sperm parameters, quantification of malondialdehyde via the thiobarbituric acid (TBA) assay, protein determination using the Bradford method, and qRT‑PCR‑based profiling of gene expression. Caffeic acid significantly decreased MDA levels in cisplatin‑exposed mice ( p < 0.05) and markedly improved testicular histoarchitecture and sperm quality indices ( p < 0.05). Additionally, antioxidant‑related genes GPX1, SOD1, and Nrf2 were substantially upregulated in the cisplatin plus caffeic acid group, while pro‑apoptotic markers caspase‑3 and BAX were reduced and anti‑apoptotic Bcl‑2 was elevated relative to the cisplatin group ( p < 0.05). Collectively, these findings indicate that caffeic acid enhances antioxidant gene expression and modulates oxidative and apoptotic pathways, thereby improving spermatogenic outcomes and mitigating cisplatin‑induced testicular damage. These results highlight caffeic acid as a promising therapeutic candidate for preventing male reproductive oxidative toxicity.