Aminoguanidine affects systemic and lung inflammation induced by lipopolysaccharide in rats

Respiratory Research

Nema Mohamadian Roshan¹  Saeideh Saadat²  Mahmoud Hosseini²  Mohammad Hossein Boskabady²  Vahid Reza Askari³  Farimah Beheshti⁴ 

[1] 0000 0001 2198 6209, grid.411583.a, Department of Pathology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran;0000 0001 2198 6209, grid.411583.a, Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, 9177948564, Mashhad, Iran;0000 0001 2198 6209, grid.411583.a, Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, 9177948564, Mashhad, Iran;0000 0001 2198 6209, grid.411583.a, Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, 9177948564, Mashhad, Iran;0000 0001 2198 6209, grid.411583.a, Student Research Committee, Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran;Neuroscience Research Center, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran;Department of Physiology, School of Paramedical Sciences, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran;

关键词: Aminoguanidine;    Inflammation;    Lipopolysaccharide;    Lung injury;    Nitric oxide;   

DOI  :  10.1186/s12931-019-1054-6

来源: publisher

【 摘 要 】

BackgroundNitric oxide is a mediator of potential importance in numerous physiological and inflammatory processes in the lung. Aminoguanidine (AG) has been shown to have anti-inflammation and radical scavenging properties. This study aimed to investigate the effects of AG, an iNOS inhibitor, on lipopolysaccharide (LPS)-induced systemic and lung inflammation in rats.MethodsMale Wistar rats were divided into control, LPS (1 mg/kg/day i.p.), and LPS groups treated with AG 50, 100 or 150 mg/kg/day i.p. for five weeks. Total nitrite concentration, total and differential white blood cells (WBC) count, oxidative stress markers, and the levels of IL-4, IFN-γ, TGF-β1, and PGE2 were assessed in the serum or bronchoalveolar lavage fluid (BALF).ResultsAdministration of LPS decreased IL-4 level (p < 0.01) in BALF, total thiol content, superoxide dismutase (SOD) and catalase (CAT) activities (p < 0.001) in BALF and serum, and increased total nitrite, malondialdehyde (MDA), IFN-γ, TGF-β1 and PGE2 (p < 0.001) concentrations in BALF. Pre-treatment with AG increased BALF level of IL-4 and total thiol as well as SOD and CAT activities (p < 0.05 to p < 0.001), but decreased BALF levels of total nitrite, MDA, IFN-γ, TGF-β1, and PGE2 (p < 0.01 to p < 0.001). AG treatment decreased total WBC count, lymphocytes and macrophages in BALF (p < 0.01 to p < 0.001) and improved lung pathological changes including interstitial inflammation and lymphoid infiltration (p < 0.05 to p < 0.001).ConclusionsAG treatment reduced oxidant markers, inflammatory cytokines and lung pathological changes but increased antioxidants and anti-inflammatory cytokines. Therefore, AG may play a significant protective role against inflammation and oxidative stress that cause lung injury.

【 授权许可】

CC BY