Benzylamine and methylamine, substrates of semicarbazide-sensitive amine oxidase, attenuate inflammatory response induced by lipopolysaccharide

Abstract

Current evidence indicates that semicarbazide-sensitive amine oxidase (SSAO) substrates possess insulin-mimic effect, which was thought to play an anti-inflammatory role. The purpose of the present study was to determine whether SSAO substrates benzylamine (BZA) and methylamine (MA) attenuate inflammatory response induced by lipopolysaccharide (LPS). BALB/c mice peritoneal macrophages (PMs) that express SSAO and RAW264.7 mouse macrophages that do not express SSAO were used in vitro studies. Experimental mice were given BZA or MA through intraperitoneal injection before LPS challenge. The results showed that BZA or MA treatment significantly reduced LPS-induced pro-inflammatory mediators (nitric oxide, TNF-α) production, the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, and glucose consumption in murine PMs, but not in RAW264.7 cell line. The metabolites of BZA or MA catalyzed by SSAO, hydrogen peroxide, formaldehyde, and benzaldehyde could also significantly decrease LPS-induced nitric oxide and TNF-α production, iNOS and COX-2 expression, and glucose consumption in vitro. In addition, BZA or MA administration could significantly decrease plasma pro-inflammatory mediators and the expression of iNOS and COX-2 in liver and lung, and could also attenuate LPS-induced transient hyperglycemia and chronic hypoglycemia. These findings indicated that substrates of SSAO might be involved in the anti-inflammatory effects. The metabolites of BZA and MA catalyzed by SSAO might be responsible for the anti-inflammatory effects. Moreover, BZA or MA administration could be useful for normalization of glucose disposal during endotoxemia.