Protective effects of agomelatin, a melatonin receptor agonist, on paracetamol induced nephrotoxicity; [Melatonin reseptor agonisti agomelatin'in parasetamol ile İndüklenmiş nefrotoksisitede koruyucu etkileri]

Paracetamol may cause kidney damage when used in supratherapeutic doses. Ago­melatine which is a melatonin analogue is an antidepressant drug. In the light of this information, we aimed to determine the protective effect of Agomelatine on high dose paracetamol-induced nephrotoxicity by biochemical method. In our study, 42 Sprague Dawley male rats were divided into 7 groups; Control, Paraceta­mol (2 g/kg), NAC+Paracetamol (140 mg/kg+2 g/kg), Agomelatine+Paracetamol (20 mg/kg+2 g/kg), Agomelatine+Paracetamol (40 mg/kg+2 g/kg), Agomelatine (40 mg/kg), NAC (140 mg/kg). Biochemical examinations were performed on tissue and blood samples obtained from all groups 24 hours after paracetamol ad­ministration. In the biochemical examination, the urea and creatinine levels were significantly increased in the group induced nephrotoxicity with paracetamol, and it was determined that serum levels of urea and creatinine decreased significantly with the administration of agomelatine according to paracetamol group. This de­crease did not change in different doses of agomelatine. In the evaluations made at the tissue level, in the group induced nephrotoxicity with paracetamol, GSH and SOD levels decreased significantly and MDA level increased significantly; It was determined that GSH and SOD levels increased significantly and MDA levels decreased significantly in the groups treated with agomelatine. As a result; It has been shown biochemically that agomelatine has a therapeutic effect in preventing nephrotoxicity caused by high dose paracetamol. This result was promising that agomelatine can be used in paracetamol poisoning seen in the clinic. © 2019, Hacettepe University, Faculty of Pharmacy. All rights reserved.