The Role of Urotensin Receptors in the Paracetamol-Induced Hepatotoxicity Model in Mice: Ameliorative Potential of Urotensin II Antagonist


PALABIYIK S. S. , Karakus E. , AKPINAR E. , HALICI Z. , BAYIR Y. , YAYLA M., et al.

BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY, cilt.118, ss.150-159, 2016 (SCI İndekslerine Giren Dergi)

  • Cilt numarası: 118 Konu: 2
  • Basım Tarihi: 2016
  • Doi Numarası: 10.1111/bcpt.12447
  • Dergi Adı: BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
  • Sayfa Sayısı: ss.150-159

Özet

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-) and IL-1 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 300mg/kg). Groups 3 and 4 were treated with only AGO (AC7954, UTR agonist) 15 and 30mg/kg intraperitoneally, respectively. Groups 5 and 6 were treated with only ANTA (SB657510, UTR antagonist) 30 and 60mg/kg intraperitoneally, respectively. Group 7 was treated with AGO 30mg/kg and ANTA 60mg/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 24hr 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 24hr 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.