title: The Role of Urotensin Receptors in the Paracetamol-Induced Hepatotoxicity Model in Mice: Ameliorative Potential of Urotensin II Antagonist.
abstract: We aimed to evaluate the possible protective effect of a UTR antagonist and to determine the effect of the antagonist on ALT and AST levels in serum, the mRNA expression level of UTR, tumour necrosis factor-alpha (TNF-α) and IL-1β and SOD activity, GSH and MDA levels in liver tissues, which are important mediators or markers for the hepatotoxicity animal model in mice. Animals fasted overnight and were divided into seven equal groups (n = 12). The first group was the healthy group (administered 0.1% DMSO intraperitoneally). Group 2 received only paracetamol (PARA) (administered orally at a dosage of 300 mg/kg). Groups 3 and 4 were treated with only AGO (AC7954, UTR agonist) 15 and 30 mg/kg intraperitoneally, respectively. Groups 5 and 6 were treated with only ANTA (SB657510, UTR antagonist) 30 and 60 mg/kg intraperitoneally, respectively. Group 7 was treated with AGO 30 mg/kg and ANTA 60 mg/kg intraperitoneally. One hour after the pre-treatment drugs were administered, groups 3 through 7 were given PARA. After the experimental period, the mice were killed 6 and 24 hr after PARA was administered. Antagonist administration significantly decreased the ALT and AST levels, while agonist administration did not. In addition, SOD activity and GSH levels increased, and the MDA level decreased with the pre-treatment of two antagonist doses. The increased UTR gene expression through PARA was significantly lower in both doses of the antagonist groups at 24 hr when compared with the agonist and PARA groups. This study showed that UTR antagonists have hepatoprotective and anti-inflammatory effects on high-dose PARA-induced hepatotoxicity in mice.
authors.affiliation: Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Ataturk University, Erzurum, Turkey.
authors.forename: Saziye S
authors.initials: SS
authors.lastname: Palabiyik
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Ataturk University, Erzurum, Turkey.
authors.forename: Emre
authors.initials: E
authors.lastname: Karakus
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Ataturk University, Erzurum, Turkey.
authors.forename: Erol
authors.initials: E
authors.lastname: Akpinar
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Ataturk University, Erzurum, Turkey.
authors.forename: Zekai
authors.initials: Z
authors.lastname: Halici
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Ataturk University, Erzurum, Turkey.
authors.forename: Yasin
authors.initials: Y
authors.lastname: Bayir
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Ataturk University, Erzurum, Turkey.
authors.forename: Muhammed
authors.initials: M
authors.lastname: Yayla
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Ataturk University, Erzurum, Turkey.
authors.forename: Duygu
authors.initials: D
authors.lastname: Kose
mesh_terms: D000082:Acetaminophen / Q000494:pharmacology*; D000410:Alanine Transaminase / Q000097:blood; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D002839:Chromans / Q000494:pharmacology*; D051379:Mice; D020011:Protective Agents / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology*; D016896:Treatment Outcome; D014579:Urotensins / Q000819:agonists / Q000037:antagonists & inhibitors
chemical_list: C468786:3-(4-chlorophenyl)-3-(2-(dimethylamino)ethyl)isochroman-1-one; D018712:Analgesics, Non-Narcotic; D002839:Chromans; D020011:Protective Agents; C553589:SB 657510; D013449:Sulfonamides; D014579:Urotensins; D000082:Acetaminophen; C029677:urotensin II; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase