Aminoguanidine affects systemic and lung inflammation induced by lipopolysaccharide in rats

Saeideh Saadat,Mohammad Hossein Boskabady,Nema Mohamadian Roshan,Farimah Beheshti,Vahid Reza Askari,Mahmoud Hosseini

doi:10.1186/s12931-019-1054-6

Abstract

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.

Highlights

Nitric oxide is a mediator of potential importance in numerous physiological and inflammatory processes in the lung
Endotoxins and cytokines induced rapid alterations in NO gene expression leading to the de novo synthesis of the inducible isoform of nitric oxide synthases and cyclooxygenase (COX-2) pathways
Total nitrite concentration The serum and bronchoalveolar lavage fluid (BALF) nitrite levels of LPS groups were increased by 238% (2060.91 ± 93.23) and 125% (311.63 ± 18.72), respectively relative to control group (864.7 ± 62.89 and 248.46 ± 4.24, for serum and BALF), (P < 0.001 and P < 0.01, respectively), (Table and Fig. 1)

Summary

Introduction

Nitric oxide is a mediator of potential importance in numerous physiological and inflammatory processes in the lung. This study aimed to investigate the effects of AG, an iNOS inhibitor, on lipopolysaccharide (LPS)-induced systemic and lung inflammation in rats. NO, a potentially toxic free radical and physiological messenger, has a major role in the regulation of the immune system functions [13] including aggregation of platelets, rolling and migration of leukocytes, and expression of inflammatory cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8), interferon gamma (INF-γ) and tumor necrosis factor-alpha (TNF-α) [14]. Endotoxins and cytokines induced rapid alterations in NO gene expression leading to the de novo synthesis of the inducible isoform of nitric oxide synthases (iNOS) and cyclooxygenase (COX-2) pathways. There are interrelated and the cross-talk between these two pathways which play a key role in the regulation of the inflammatory processes [13]

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