title: Agmatine attenuates silica-induced pulmonary fibrosis.
abstract: There is a large body of evidence that nitric oxide (NO) formation is implicated in mediating silica-induced pulmonary fibrosis. As a reactive free radical, NO may not only contribute to lung parenchymal tissue injury but also has the ability to combine with superoxide and form a highly reactive toxic species peroxynitrite that can induce extensive cellular toxicity in the lung tissues. This study aimed to explore the effect of agmatine, a known NO synthase inhibitor, on silica-induced pulmonary fibrosis in rats. Male Sprague Dawley rats were treated with agmatine for 60 days following a single intranasal instillation of silica suspension (50 mg in 0.1 ml saline/rat). The results revealed that agmatine attenuated silica-induced lung inflammation as it decreased the lung wet/dry weight ratio, protein concentration, and the accumulation of the inflammatory cells in the bronchoalveolar lavage fluid. Agmatine showed antifibrotic activity as it decreased total hydroxyproline content of the lung and reduced silica-mediated lung inflammation and fibrosis in lung histopathological specimen. In addition, agmatine significantly increased superoxide dismutase (p < 0.001) and reduced glutathione (p < 0.05) activities with significant decrease in the lung malondialdehyde (p < 0.001) content as compared to the silica group. Agmatine also reduced silica-induced overproduction of pulmonary nitrite/nitrate as well as tumor necrosis factor α. Collectively, these results demonstrate the protective effects of agmatine against the silica-induced lung fibrosis that may be attributed to its ability to counteract the NO production, lipid peroxidation, and regulate cytokine effects.
authors: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt dinaagamy1@yahoo.com.
authors: D S
authors: DS
authors: El-Agamy
authors: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
authors: M H
authors: MH
authors: Sharawy
authors: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
authors: E M
authors: EM
authors: Ammar
mesh_terms: D000376:Agmatine / Q000494:pharmacology*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D019610:Cytoprotection; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D006909:Hydroxyproline / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D011014:Pneumonia / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control; D011654:Pulmonary Edema / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D017207:Rats, Sprague-Dawley; D012822:Silicon Dioxide; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors
chemical_list: D015415:Biomarkers; D004791:Enzyme Inhibitors; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D008315:Malondialdehyde; D000376:Agmatine; D012822:Silicon Dioxide; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D005978:Glutathione; D006909:Hydroxyproline
keywords: Agmatine; nitric oxide; pulmonary fibrosis; rats; silica