Aminoguanidine affects systemic and lung inflammation induced by lipopolysaccharide in rats

Abstract

Background Nitric 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. Methods Male 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). Results Administration 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). Conclusions AG 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.

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“…Measurement of total thiol content in serum was done using 2,2′‐dinitro‐5,5′‐dithiodibenzoic acid based on a previously established method. This reagent reacts with the SH groups and creates a highly colored anion with a peak absorbance at 412 nm 23,24 . Total thiol content is expressed in micromoles.…”

“…Superoxide dismutase activity was measured in serum based on the production of superoxide by auto‐oxidation of pyrogallol and dependent revived inhibition of 3‐(4,5‐dimethyl‐thiazol‐2‐yl) 2,5‐diphenyl tetrazolium bromide to formazan, according to a previously described method 23,25 …”

“…Determination of catalase activity in serum was performed based on the ability of the enzyme to break down hydrogen peroxide (H 2 O 2 ). The decomposition of H 2 O 2 was shown by the reduction of absorption at 240 nm 23,26 . Superoxide dismutase and catalase activities are expressed as units per milliliter.…”

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