In vitro screening of NADPH oxidase inhibitors and in vivo effects of L-leucinethiol on experimental autoimmune encephalomyelitis-induced mice

Abstract

Experimental autoimmune encephalomyelitis (EAE), a Th1 polarized demyelinating disease of the central nervous system, shares many pathological and clinical similarities with multiple sclerosis (MS). The objectives of this study were i) to evaluate the suppressive effects of L-leucinethiol (LeuSH), a metalloprotease inhibitor on EAE-induced mice and ii) to study the effects of LeuSH on matrix metalloproteinase-9 (MMP-9), NADPH oxidase and cytokines (IFN-gamma, IL-5 and IL-10) in tissues and plasma of EAE mice as a measure of potential markers associated with EAE disease. C57BL/6 mice were immunized with myelin oligodendrocyte glycoprotein (MOG35-55) peptide in complete Freund's adjuvant to induce EAE. A significant difference was observed in body weights and clinical signs of LeuSH (8 mg/kg) administered EAE-induced mice compared to control mice. The findings of this study include alterations in the enzymatic expression of MMP-9, NADPH oxidase and cytokine levels in the brain, spinal cord, spleen, thymus and plasma of inhibitor-treated EAE mice as well as EAE-induced mice. The enzyme activities of NADPH oxidase were inhibited by LeuSH. From these results, it can be considered that LeuSH acts as one of the antigen candidates in ameliorating the clinical symptoms of EAE disease in mice. (C) 2012 Published by Elsevier B.V.