Taurine protects against gentamicin-induced neurotoxicity through dual modulation of Nrf2 and NF-κB pathways

Gentamicin (GM), an aminoglycoside antibiotic, is associated with neurotoxic effects that result in cognitive and behavioral impairments. Taurine, a sulfur-containing amino acid, has demonstrated neuroprotective properties. This study investigates the potential of taurine to mitigate GM-induced neurotoxicity in Sprague Dawley rats. Thirty-two male rats were randomly assigned to four groups: control, taurine (100 mg/kg/day orally for 15 days), GM (120 mg/kg/day intraperitoneally for 15 days), and taurine + GM (co-administered at the aforementioned doses and routes). Behavioral assessments (open field and Y-maze tests) were conducted to evaluate locomotor activity, anxiety, and memory. Hippocampal tissue was analyzed using histopathology, immunohistochemistry, and biochemical assays. Quantitative analyses via ELISA, RT-qPCR, and immunohistochemical scoring confirmed that GM administration induced anxiety-like behaviors, hippocampal degeneration, oxidative stress (elevated MDA, reduced SOD/CAT), neuroinflammation (elevated NF-ĸB, TNF-α, IL-1β, IL-6), and increased neuronal apoptosis (raised caspase-3, Bax; reduced Bcl-2). Taurine co-treatment effectively reversed these effects, improving behavioral outcomes, preserving neuronal structure, significantly restoring antioxidant enzyme activity and the Nrf2/HO-1 pathway, suppressing NF-ĸB-mediated inflammation, and modulating apoptotic pathways. These findings indicate that taurine provides substantial neuroprotection against GM-induced toxicity by enhancing antioxidant capacity, reducing neuroinflammation, and inhibiting neuronal apoptosis. Future research should explore taurine's dose-response effects, long-term neurobehavioral outcomes, and its molecular interactions with key targets like NF-κB and Nrf2.