Is montelukast as effective as N-acetylcysteine in hepatic injury due to acetaminophen intoxication in rats?

Exp Toxicol Pathol. 2016 Jan;68(1):55-9. doi: 10.1016/j.etp.2015.09.008. Epub 2015 Oct 14.

Abstract

This study aims to investigate the acute protective effect of montelukast sodium in hepatic injury secondary to acetaminophen (APAP) intoxication. This study used 60 rats. The rats were grouped into 6 groups. The control group was administered oral distilled water 10 ml/kg, the APAP group oral APAP 1 g/kg, the montelukast sodium (MK) group oral MK 30 mg/kg, the acetaminophen+N-acetylcysteine (APAP+NAC) group oral APAP 1 g/kg, followed by a single dose of intraperitoneal NAC 1.5 g/kg three hours later, the acetaminophen+montelukast sodium (APAP+MK) group oral APAP 1 g/kg, followed by oral MK 30 mg/kg 3 h later, the acetaminophen+N-acetylcysteine+montelukast sodium (APAP+NAC+MK) group oral APAP 1 g/kg, followed by a single intraperitoneal NAC 1.5 g/kg plus oral MK 30 mg/kg 3 h later. Blood and liver tissue samples were taken 24h after drug administration. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total bilirubin were studied from the blood samples. Liver tissue samples were used for histopathological examination. Compared with the control group, serum AST and ALT activities were higher in the APAP and APAP+NAC groups. APAP+NAC, APAP+MK, and APAP+NAC+MK groups had reduced serum ALT and AST activities than the group administered APAP alone. APAP+MK and APAP+NAC+MK groups had a lower serum ALP activity than the control group. Histopathologically, there was a difference between the group administered APAP alone and the APAP+MK and APAP+NAC+MK groups. MK is as protective as NAC in liver tissue in APAP intoxication in rats.

Keywords: Acetaminophen; Hepatotoxicity; Histopathology; Montelukast sodium; NAC.

MeSH terms

  • Acetaminophen / toxicity*
  • Acetates / pharmacology*
  • Acetylcysteine / pharmacology
  • Analgesics, Non-Narcotic / toxicity*
  • Animals
  • Chemical and Drug Induced Liver Injury / prevention & control*
  • Cyclopropanes
  • Cytochrome P-450 CYP1A2 Inducers / pharmacology*
  • Disease Models, Animal
  • Free Radical Scavengers / pharmacology
  • Male
  • Quinolines / pharmacology*
  • Rats
  • Rats, Wistar
  • Sulfides

Substances

  • Acetates
  • Analgesics, Non-Narcotic
  • Cyclopropanes
  • Cytochrome P-450 CYP1A2 Inducers
  • Free Radical Scavengers
  • Quinolines
  • Sulfides
  • Acetaminophen
  • montelukast
  • Acetylcysteine