Montelukast and irbesartan ameliorate metabolic and hepatic disorders in fructose-induced metabolic syndrome in rats

Mohamed A. Ibrahim, Entesar F. Amin, Salwa A. Ibrahim, Walaa Y. Abdelzaher, Aly M. Abdelrahman

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Metabolic syndrome (MetS) is a global health problem. Elucidation of the role of 5- lipooxygenase/leukotriene pathway and renin angiotensin system in the pathogenesis of MetS suggests a variety of potential therapies worthy of testing. The present work investigated the effect of montelukast, a leukotriene antagonist and/or irbesartan, an angiotensin II-receptor blocker, in the prevention of fructose-induced MetS in rats. Rats were allocated into 9 groups and treated for 6 weeks as follow: normal control; MetS group (received 20% fructose); MetS+montelukast groups (treated with montelukast, 5, 10, and 20 mg/kg/day, respectively); MetS+irbesartan groups (treated withirbesartan 15, 30, and 45 mg/kg/day, respectively); and MetS+montelukast+irbesartan group (co treated with montelukast 5 mg/kg plus irbesartan 15 mg/g). Metabolic parameters (visceral fat index, liver index, insulin resistance, and serum lipid profile), oxidative stress markers (malondialdehyde, reduced glutathione, and catalase), and inflammatory mediators (tumor necrosis factor-α, and uric acid) were measured. Expression of caspase-3 in hepatic tissues was detected by immunohistochemistry. Liver injury was evaluated by histopathological examination and serum alanine aminotransferase (ALT). Montelukast, irbesartan, and their combination caused significant attenuation in metabolic and hepatic disorders. Their effect was associated with attenuation of oxidative stress markers, inflammatory mediators, and caspase-3 expression. This study highlighted the protective effects of montelukast and irbesartan against fructose-induced metabolic and hepatic disorders. The protective effect of either drug relies, at least in part, on their antioxidant and antiinflammatory effect, as well as on the reduction of caspase-3 expression in hepatic tissue.

Original languageEnglish
Pages (from-to)204-210
Number of pages7
JournalEuropean Journal of Pharmacology
Volume724
Issue number1
DOIs
Publication statusPublished - Feb 5 2014

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Keywords

  • Fructose-induced metabolic syndrome
  • Irbesartan
  • Montelukast

ASJC Scopus subject areas

  • Pharmacology

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