The Protective Effects of N-Acetylserotonin Against Cisplatin-Induced Renal Injury: A Biochemical and...

Cisplatin is a potent chemotherapeutic agent whose clinical application is frequently limited by severe nephrotoxicity. N-acetylserotonin (NAS), a precursor of melatonin and a selective agonist of the TrkB receptor, has demonstrated significant antioxidant and neuroprotective properties. This study aimed to evaluate the potential renoprotective effects of NAS against cisplatin-induced acute kidney injury (AKI) in a rat model. Thirty-five Wistar Albino rats were divided into five groups: Control, Sham, NAS (5 mg/kg), Cisplatin (CP; 7.5 mg/kg), and CP + NAS. NAS was administered daily for seven days, while cisplatin was given as a single dose on the fourth day. Renal function was assessed via serum urea and creatinine. Oxidative stress markers, including Malondialdehyde (MDA), Superoxide Dismutase (SOD), Total Antioxidant Status (TAS), and Total Oxidant Status (TOS), were measured in kidney tissue. Comprehensive histopathological evaluations were performed to assess tubular and glomerular damage. Cisplatin administration significantly increased serum creatinine levels and induced severe histopathological damage (p < 0.05). While cisplatin reduced SOD and TAS levels, NAS treatment showed a trend toward biochemical recovery without reaching statistical significance in oxidative markers. Notably, NAS administration significantly ameliorated cisplatin-induced histopathological lesions, specifically reducing tubular epithelial loss, glomerular degeneration, interstitial inflammation, and vacuolization (p < 0.05). Our findings indicate that NAS exerts a profound structural protective effect against cisplatin-induced renal injury. The preservation of renal parenchyma, despite modest systemic biochemical shifts, suggests that NAS-mediated protection may involve localized TrkB-dependent pro-survival signaling and stabilization of mitochondrial integrity. NAS represents a promising therapeutic candidate for mitigating chemotherapy-induced nephrotoxicity.