title: Montelukast attenuates lipopolysaccharide-induced cardiac injury in rats.
abstract: This study investigates the possible protective effects of montelukast (MNT) against lipopolysaccharide (LPS)-induced cardiac injury, in comparison to dexamethasone (DEX), a standard anti-inflammatory. Male Sprague Dawley rats (160-180 g) were assigned to five groups (n = 8/group): (1) control; (2) LPS (10 mg/kg, intraperitoneal (i.p.)); (3) LPS + MNT (10 mg/kg, per os (p.o.)); (4) LPS + MNT (20 mg/kg, p.o.); and (5) LPS + DEX (1 mg/kg, i.p.). Twenty-four hours after LPS injection, heart/body weight (BW) ratio and percent survival of rats were determined. Serum total protein, creatine kinase muscle/brain (CK-MB), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) activities were measured. Heart samples were taken for histological assessment and for determination of malondialdehyde (MDA) and glutathione (GSH) contents. Cardiac tumor necrosis factor α (TNF-α) expression was evaluated immunohistochemically. LPS significantly increased heart/BW ratio, serum CK-MB, ALP, and LDH activities and decreased percent survival and serum total protein levels. MDA content increased in heart tissues with a concomitant reduction in GSH content. Immunohistochemical staining of heart specimens from LPS-treated rats revealed high expression of TNF-α. MNT significantly reduced percent mortality and suppressed the release of inflammatory and oxidative stress markers when compared with LPS group. Additionally, MNT effectively preserved tissue morphology as evidenced by histological evaluation. MNT (20 mg/kg) was more effective in alleviating LPS-induced heart injury when compared with both MNT (10 mg/kg) and DEX (1 mg/kg), as evidenced by decrease in positive staining by TNF-α immunohistochemically, decrease MDA, and increase GSH content in heart tissue. This study demonstrates that MNT might have cardioprotective effects against the inflammatory process during endotoxemia. This effect can be attributed to its antioxidant and/or anti-inflammatory properties.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Delta University, Mansoura, Egypt.
authors.forename: A E
authors.initials: AE
authors.lastname: Khodir
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
authors.forename: H A
authors.initials: HA
authors.lastname: Ghoneim
authors.affiliation: Urology and Nephrology Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
authors.forename: M A
authors.initials: MA
authors.lastname: Rahim
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt ghmsuddek@yahoo.com.
authors.forename: G M
authors.initials: GM
authors.lastname: Suddek
mesh_terms: D000085:Acetates / Q000494:pharmacology*; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D001835:Body Weight; D052279:Creatine Kinase, MB Form / Q000097:blood; D003521:Cyclopropanes; D003907:Dexamethasone / Q000494:pharmacology*; D005978:Glutathione; D006321:Heart / Q000033:anatomy & histology / Q000187:drug effects; D006331:Heart Diseases / Q000139:chemically induced* / Q000401:mortality; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D008315:Malondialdehyde; D009929:Organ Size / Q000187:drug effects; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013440:Sulfides; D014409:Tumor Necrosis Factor-alpha
chemical_list: D000085:Acetates; D001798:Blood Proteins; D003521:Cyclopropanes; D008070:Lipopolysaccharides; D011804:Quinolines; D013440:Sulfides; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D003907:Dexamethasone; D007770:L-Lactate Dehydrogenase; D052279:Creatine Kinase, MB Form; D000469:Alkaline Phosphatase; D005978:Glutathione; C093875:montelukast
keywords: Lipopolysaccharide; cardiac injury; inflammation; montelukast; oxidative stress; rats