Protective role of aprepitant in paracetamol-induced renal injury: biochemical and histopathological evidence

Paracetamol (PARA) is a commonly used analgesic and antipyretic, but overdose can result in severe hepatotoxicity and nephrotoxicity. Aprepitant (APRE), a selective neurokinin-1 receptor (NK-1R) antagonist used clinically as an antiemetic, may offer protective effects against drug-induced organ toxicity. This study aimed to evaluate the renoprotective potential of APRE in a rat model of PARA-induced nephrotoxicity. In this study, 36 male Albino Wistar rats were randomly assigned to six groups: Healthy, PARA (2 g/kg), APRE (20 mg/kg), N-acetylcysteine (NAC) + PARA (140 mg/kg + 2 g/kg), APRE + PARA (10 mg/kg + 2 g/kg), and APRE + PARA (20 mg/kg + 2 g/kg). Twenty-four hours after PARA administration, tissue and blood samples were collected from all groups for biochemical and histopathological analyses. Serum BUN and creatinine levels increased in the PARA group, whereas they improved in the NAC and APRE groups. Renal superoxide dismutase (SOD) activity and glutathione (GSH) levels decreased, but NAC and APRE significantly improved these parameters. Moreover, while malondialdehyde (MDA) levels in kidney tissue increased in the PARA group, they were significantly reduced in the NAC and APRE groups. In addition, histopathological changes supported the biochemical findings. APRE may protect the kidneys against PARA-induced damage by reducing oxidative stress and improving antioxidant defenses.