title: Effect of betulinic acid on neutrophil recruitment and inflammatory mediator expression in lipopolysaccharide-induced lung inflammation in rats.
abstract: This study aimed to evaluate the effect of betulinic acid (BA) on acute lung damage induced by bacterial endotoxin (lipopolysaccharide, LPS) in male Sprague-Dawley rats and explore its possible mechanisms. Oral administration of 25 (mg/kg) BA started 7 days before LPS or saline nasal installation. Twenty-four hours after LPS or saline installation, samples of lung tissues were collected for determination of level of lipid peroxidation (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), and expression of tumor necrosis-α (TNF-α), transforming growth factor-β1 (TGF-β1) and inducible nitric oxide synthase (iNOS). Histopathology was done to examine pathological changes in lungs. Wet/dry (W/D) ratio and capillary protein leakage were also determined. Bronchoalveolar lavage (BAL) fluid was carried out for quantification of airway cellular inflammation and nitrate/nitrite (NOx) level. In comparison to BAL fluid samples from control animals, LPS-stimulated animals exhibited a higher count of the inflammatory cells and increased NOx levels. Lungs from LPS-treated animals showed increased lipid peroxidation, altered activities of antioxidant enzymes (GSH and SOD) and increased expression of TNF-α, TGF-β1 and iNOS in comparison to lungs from control animals. LPS installation-induced pulmonary edema, manifested by significant increase in lung W/D ratio and Evans blue extravasation in lung tissue. This was supported by the histopathological examination which revealed markedly inflamed lung in LPS-treated animals. Treatment with BA was found to significantly attenuate all these alterations. The present results suggest that BA is endowed with antiinflammatory and antioxidant properties that protect the lung against the deleterious actions of LPS.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt. manarahna@yahoo.com
authors.forename: Manar A
authors.initials: MA
authors.lastname: Nader
authors.forename: Hany N
authors.initials: HN
authors.lastname: Baraka
mesh_terms: D055371:Acute Lung Injury / Q000276:immunology; D000704:Analysis of Variance; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016166:Free Radical Scavengers / Q000032:analysis; D005978:Glutathione / Q000032:analysis; D015227:Lipid Peroxidation / Q000187:drug effects; D008070:Lipopolysaccharides / Q000276:immunology; D008168:Lung / Q000737:chemistry / Q000473:pathology; D008297:Male; D020556:Neutrophil Infiltration / Q000187:drug effects*; D009569:Nitric Oxide / Q000032:analysis; D052247:Nitric Oxide Synthase Type II / Q000032:analysis; D053978:Pentacyclic Triterpenes; D011014:Pneumonia / Q000139:chemically induced / Q000188:drug therapy*; D011654:Pulmonary Edema / Q000139:chemically induced; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000032:analysis; D053773:Transforming Growth Factor beta1 / Q000032:analysis; D014315:Triterpenes / Q000494:pharmacology / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D000094062:Betulinic Acid
chemical_list: D016166:Free Radical Scavengers; D008070:Lipopolysaccharides; D053978:Pentacyclic Triterpenes; D053773:Transforming Growth Factor beta1; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D013482:Superoxide Dismutase; D005978:Glutathione; D000094062:Betulinic Acid