title: Montelukast and irbesartan ameliorate metabolic and hepatic disorders in fructose-induced metabolic syndrome in rats.
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.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Minia University, El-Minia, Egypt. Electronic address: maim69@yahoo.com.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Ibrahim
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Minia University, El-Minia, Egypt.
authors.forename: Entesar F
authors.initials: EF
authors.lastname: Amin
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Minia University, El-Minia, Egypt.
authors.forename: Salwa A
authors.initials: SA
authors.lastname: Ibrahim
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Minia University, El-Minia, Egypt.
authors.forename: Walaa Y
authors.initials: WY
authors.lastname: Abdelzaher
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Minia University, El-Minia, Egypt.
authors.forename: Aly M
authors.initials: AM
authors.lastname: Abdelrahman
mesh_terms: D000085:Acetates / Q000494:pharmacology / Q000627:therapeutic use*; D000410:Alanine Transaminase / Q000097:blood; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D001786:Blood Glucose / Q000032:analysis; D053148:Caspase 3 / Q000378:metabolism; D003521:Cyclopropanes; D005632:Fructose; D007328:Insulin / Q000097:blood; D000077405:Irbesartan; D020024:Leukotriene Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011804:Quinolines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013440:Sulfides; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000085:Acetates; D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds; D001786:Blood Glucose; D003521:Cyclopropanes; D007328:Insulin; D020024:Leukotriene Antagonists; D008055:Lipids; D011804:Quinolines; D013440:Sulfides; D013777:Tetrazoles; D005632:Fructose; D000410:Alanine Transaminase; D053148:Caspase 3; D000077405:Irbesartan; C093875:montelukast
keywords: Fructose-induced metabolic syndrome; Irbesartan; Montelukast