title: Montelukast reduces sepsis-induced lung and renal injury in rats.
abstract: This study was undertaken to examine the effects of montelukast (MNT) on lung and kidney injury in lipopolysaccharide (LPS) induced systemic inflammatory response. Rats were randomized into 5 groups (n = 8 rats/group): (i) Control; (ii) LPS treated (10 mg/kg body mass, by intraperitoneal (i.p.) injection); (iii) LPS + MNT (10 mg/kg, per oral (p.o.)); (iv) LPS + MNT (20 mg/kg, p.o); (v) LPS + dexamethasone (DEX; 1 mg/kg, i.p.). Twenty-four hours after sepsis was induced, the lung or kidney:body mass ratio and percent survival of rats were determined. Creatinine, blood urea nitrogen (BUN), albumin, total protein, and LDH activity were measured. Lung and kidney samples were taken for histological assessment and for determination of their malondialdehyde (MDA) and glutathione (GSH) contents. The expression of tumour necrosis factor α (TNF-α) in tissue was evaluated immunohistochemically. LPS significantly increased the organ:body mass ratio, serum creatinine, BUN, and LDH, and decreased serum albumin and total protein levels. MDA levels increased in lung and kidney tissues after treatment with LPS, and there was a concomitant reduction in GSH levels. Immunohistochemical staining of lung and kidney specimens from LPS-treated rats revealed high expression levels of TNF-α. MNT suppresses the release of inflammatory and oxidative stress markers. Additionally, MNT effectively preserved tissue morphology as evidenced by histological evaluation. These results demonstrate that MNT could have lung and renoprotective effects against the inflammatory process during endotoxemia. This effect can be attributed to its antioxidant and (or) anti-inflammatory properties.
authors.affiliation: a Department of Pharmacology and Toxicology, Faculty of Pharmacy, Delta University, Mansoura, Egypt.
authors.forename: Ahmed E
authors.initials: AE
authors.lastname: Khodir
authors.forename: Hamdy A
authors.initials: HA
authors.lastname: Ghoneim
authors.forename: Mona Abdel
authors.initials: MA
authors.lastname: Rahim
authors.forename: Ghada M
authors.initials: GM
authors.lastname: Suddek
mesh_terms: D000085:Acetates / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D001835:Body Weight; D003521:Cyclopropanes; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D011804:Quinolines / Q000494:pharmacology* / Q000627:therapeutic use; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D013440:Sulfides; D018746:Systemic Inflammatory Response Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D000085:Acetates; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D003521:Cyclopropanes; D008070:Lipopolysaccharides; D011804:Quinolines; D013440:Sulfides; C093875:montelukast
keywords: dommage pulmonaire et rénal; inflammation; lipopolysaccharide; lung and kidney injury; montelukast; montélukast; oxidative stress; stress oxydant