Protective Effects of Agomelatin, a Melatonin Receptor Agonist, on Paracetamol Induced Nephrotoxicity

Abstract

Paracetamol may cause kidney damage when used in supratherapeutic doses. Agomelatine is an antidepressant drug that is a melatonin receptor analogue. In the light of this information, we aimed to determine the protective effect of Agomelatine on nephrotoxicity induced by high dose paracetamol biochemically. In our study, 42 Sprague Dawley male rats were divided into 7 group; Control, Paracetamol (2 g/kg), NAC+Paracetamol (140 mg/kg+2 g/kg), Agomelatine+Paracetamol (20 mg/kg+2 g/kg), Agomelatin+Paracetamol (40 mg/kg+2 g/kg), Agomelatine (40 mg/kg), NAC (140 mg/kg). Biochemical examinations were performed on tissue and blood samples 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 agomelatin. 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.

Keywords

• Agomelatine
• kidney
• nephrotoxicity
• paracetamol
• rat

Melatonin Reseptor Agonisti Agomelatin'in Parasetamol ile İndüklenmiş Nefrotoksisitede Koruyucu Etkileri

Abstract

Parasetamol supraterapötik dozlarda kullanıldığında böbreklerde hasara neden olabilmektedir. Agomelatin ise melatonin reseptör analogu olan antidepresan etkili bir ilaçtır. Bu bilgiler ışığında Agomelatin’in yüksek doz parasetamol ile oluşturulan nefrotoksisite üzerine koruyucu etkisini biyokimyasal olarak belirlemeyi amaçladık. Çalışmamızda 42 adet Sprague Dawley cinsi erkek rat 7 gruba ayrıldı; Kontrol, Parasetamol (2 g/kg), NAC+Parasetamol (140 mg/kg+2 g/kg), Agomelatin+Parasetamol (20 mg/kg+2 g/kg), Agomelatin+Parasetamol (40 mg/
kg+2g/kg), Agomelatin (40 mg/kg), NAC (140 mg/kg). Parasetamol uygulamasından 24 saat sonra tüm gruplardan alınan doku ve kan örneklerinde biyokimya sal incelemeler yapıldı. Yapılan biyokimyasal incelemede, parasetamol ile nefrotoksisite oluşturulmuş grupta üre ve kreatinin değerlerinin anlamlı şekilde yükseldiği, agomelatin ile tedavi edilen gruplarda ise; üre ve kreatinin serum seviyelerinin sadece parasetamol verilen gruba göre anlamlı şekilde azaldığı tespit edildi. Bu azalış miktarı, agomelatinin farklı dozlarında değişiklik göstermedi. Doku düzeyinde yapılan değerlendirmelerde de parasetamol ile nefrotoksisite oluşturulmuş grupta GSH ve SOD seviyelerinin anlamlı olarak düştüğü ve MDA seviyesinin anlamlı şekilde yükseldiği, agomelatin ile tedavi edilen gruplarda ise; GSH ve SOD seviyesinin anlamlı olarak yükseldiği ve MDA seviyelerinin anlamlı şekilde azaldığı tespit edildi. Sonuç olarak; yüksek doz parasetamolün neden olduğu nefrotoksisitenin önlenmesinde agomelatinin tedavi edici etkisinin olduğu biyokimyasal olarak gösterildi. Bu sonuç, klinikte görülen parasetamol zehirlenmesinde agomelatin kullanılabileceği konusunda umut verici olmuştur.

Keywords

• Agomelatin
• böbrek
• nefrotoksisite
• parasetamol
• rat

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