Protective effects of crocin against gentamicin-induced damage in rat testicular tissue: Modulating the levels of NF-κB/TLR-4 and Bax/Bcl-2/caspase-3 signaling pathways.

This study investigated the protective effects of crocin (CRO) on gentamicin (GM)-induced testicular toxicity in adult rats, focusing on oxidative stress, apoptosis, and inflammatory pathways such as Nuclear Factor Kappa B (NF-κB)/Toll-Like Receptor 4 (TLR-4) and Bcl-2-associated X protein (Bax)/B-cell lymphoma 2 (Bcl-2)/Caspase-3. Thirty-six male Sprague Dawley rats were divided into six groups: saline only, 25 mg/kg CRO, 50 mg/kg CRO, 80 mg/kg GM, 80 mg/kg GM + 25 mg/kg CRO, 80 mg/kg GM + 50 mg/kg CRO. Treatments were administered intraperitoneally for 8 days. GM increased malondialdehyde (MDA) levels, ischemia-modified albumin (IMA) levels and reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities in testicular tissue, indicating oxidative stress. Histopathology showed testicular degeneration. It also elevated Bax, Caspase-3, NF-κB, and TLR-4 expression while decreasing Bcl-2 levels, promoting apoptosis and inflammation. CRO treatment counteracted these effects by enhancing antioxidant enzyme activity, restoring GSH levels, and reducing MDA. Furthermore, CRO exhibited antiapoptotic and anti-inflammatory properties by modulating Bax/Bcl-2 and Caspase-3, and downregulating NF-κB/TLR-4 pathways. This study underscores crocin's protective effects against gentamicin-induced testicular toxicity through the modulation of key signaling pathways, suggesting its potential as a therapeutic strategy for aminoglycoside-induced reproductive damage.