In vitro screening of NADPH oxidase inhibitors and in vivo effects of L-leucinethiol on experimental autoimmune encephalomyelitis-induced mice
- In vitro screening of NADPH oxidase inhibitors and in vivo effects of L-leucinethiol on experimental autoimmune encephalomyelitis-induced mice
- L. Kandagaddala; 서지은; 마무눌 하크; 임혜연; 강민정; 정병화; T. A. patterson; 권오승
- EAE; Multiple sclerosis; L-Leucinethiol; MMP-9; NADPH Oxidase; Cytokine
- Issue Date
- Society of Toxicology
- Experimental autoimmune encephalomyelitis (EAE), a Th1 polarized demyelinating disease of the
central nervous system, shares many pathological and clinical similarities with multiple sclerosis (MS), and thus
represents an attractive animal model for this disease. 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‐γ, 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. MOG33‐55 was
administered subcutaneously on two sites over the back. Pertussis toxin was administered intraperitoneally
immediately after MOG35‐55 injection and again two days later. A significant difference was observed in body weights
and clinical signs of LeuSH (8 mg/kg) administered EAE‐induced mice compared to EAE‐induced mice. MMP‐9, NADPH
oxidase and cytokines were measured in central nervous system tissues, peripheral tissues and plasma of EAE‐induced
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.
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