title: Agomelatine: an antidepressant with new potent hepatoprotective effects on paracetamol-induced liver damage in rats.
abstract: Paracetamol was shown to induce hepatotoxicity or more severe fatal acute hepatic damage. Agomelatine, commonly known as melatonin receptor agonist, is a new antidepressant, which resynchronizes circadian rhythms with subjective and objective improvements in sleep quality and architecture, as melatonin does. In the present study, it was aimed to evaluate the hepatoprotective activity of agomelatine on paracetamol-induced hepatotoxicity and to understand the relationship between the hepatoprotective mechanism of agomelatine and antioxidant system and proinflammatory cytokines. A total of 42 rats were divided into 7 groups as each composed of 6 rats: (1) intact, (2) 40 mg/kg agomelatine, (3) 140 mg/kg N-acetylcysteine (NAC), (4) 2 g/kg paracetamol, (5) 2 g/kg paracetamol + 140 mg/kg NAC, (6) 2 g/kg paracetamol + 20 mg/kg agomelatine, and (7) 2 g/kg paracetamol + 40 mg/kg agomelatine groups. Paracetamol-induced hepatotoxicity was applied and liver and blood samples were analyzed histopathologically and biochemically. There were statistically significant increases in the activities of aspartate aminotransferase, alanine aminotransferase, levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) and 8-iso-prostane, and decreases in the activity of superoxide dismutase and level of glutathione in the group treated with paracetamol. Administration of agomelatine and NAC separately reversed these changes significantly. In conclusion, agomelatine administration protects liver cells from paracetamol-induced hepatotoxicity via antioxidant activity and reduced proinflammatory cytokines, such as TNF-α and IL-6.
authors.affiliation: Department of Pharmacology and Toxicology, Ataturk University School of Veterinary Medicine, Erzurum, Turkey.
authors.forename: E
authors.initials: E
authors.lastname: Karakus
authors.forename: Z
authors.initials: Z
authors.lastname: Halici
authors.forename: A
authors.initials: A
authors.lastname: Albayrak
authors.forename: B
authors.initials: B
authors.lastname: Polat
authors.forename: Y
authors.initials: Y
authors.lastname: Bayir
authors.forename: I
authors.initials: I
authors.lastname: Kiki
authors.forename: E
authors.initials: E
authors.lastname: Cadirci
authors.forename: A
authors.initials: A
authors.lastname: Topcu
authors.forename: S
authors.initials: S
authors.lastname: Aksak
mesh_terms: D000081:Acetamides / Q000494:pharmacology / Q000627:therapeutic use*; D000082:Acetaminophen; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D009281:Naphthalenes
chemical_list: D000081:Acetamides; D000082:Acetaminophen; D000410:Alanine Transaminase; D000928:Antidepressive Agents; D001219:Aspartate Aminotransferases; D015237:Dinoprost; D005978:Glutathione; D015850:Interleukin-6; D020011:Protective Agents; D013482:Superoxide Dismutase; D014409:Tumor Necrosis Factor-alpha; C084711:agomelatine; D009281:Naphthalenes; C075750:8-epi-prostaglandin F2alpha
keywords: 8-iso-prostaglandin F2α; Agomelatine; IL-6; TNF-α; hepatotoxicity; paracetamol