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Use of vitamins for correction of the functional state of cytochrome P450 systems at experimental allergic encephalomyelitis

机译:维生素在实验性变应性脑脊髓炎中纠正细胞色素P450系统功能状态的用途

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It is known that inflammatory cytokines, which level is significantly increased in the pathogenesis of multiple sclerosis (MS), as well as interferon-β, which is used to treat autoimmune diseases, can inhibit cytochrome P450-dependent processes of detoxification and biotransformation. The uncontrolled decrease of the activity of these processes may have a negative affect on the state of patients, so it is urgent to study the functional state of the cytochrome P450 system and to develop effective means for its regulation in these conditions. The effect of vitamin Dsub3/sub and efficiency of its composition with vitamins Bsub1/sub, Bsub2/sub, Bsub6/sub, PP, E, α-lipoic, α-linolenoic acid and mineral substances (Mg, Zn, Se) in prevention of a functional state changes of cytochrome P450- and bsub5/sub-dependent systems of the rat brain and liver endoplasmic reticulum at EAE are investigated. It has been shown that the essential decrease of the level of these cytochromes is observed both in the brain and liver. In addition the level of activity of NADH-and NADPH-oxidoreductases, which are part of microsomal electron transport chain components and coupled with monooxigenases, was reduced. These changes confirm the disturbances of a redox state and functional activity of detoxication and biotransformation systems in the studied animal tissues. Supplement of vitamin Dsub3/sub as well as the composition of biologically active substances, which we developed earlier, effectively eliminated the decrease of the level of cytochromes and activities of NADH-oxidoreductase in immunised rat tissues. Normalization of these disturbances can be explained by antioxidant and membrane-stabilizing properties of applied substances, and also by the ability to reduce the activity of inflammatory reactions by regulation of the level of inflammatory cytokines in rat organism at EAE. Thus the studied vitamin-mineral composition appeared to be more effective to normalize the found disturbances and it can be useful for prevention of exacerbations and for improvement of a status of patients with multiple sclerosis and other diseases, which are accompanied with hyperactivation of immune system.
机译:众所周知,在多发性硬化症(MS)的发病机理中,炎症细胞因子的水平显着增加,而用于治疗自身免疫性疾病的干扰素-β可以抑制细胞色素P450依赖的解毒和生物转化过程。这些过程的活动不受控制的减少可能对患者的状态产生负面影响,因此迫切需要研究细胞色素P450系统的功能状态,并为在这些条件下进行调节提供有效的手段。维生素D 3 的作用及其与维生素B 1 ,B 2 ,B 6 , PP,E,α-硫辛酸,α-亚麻酸和矿物质(Mg,Zn,Se)预防大鼠脑细胞色素P450-和b 5 依赖系统功能状态的改变对EAE的肝内质网进行了研究。已经显示在脑和肝中都观察到这些细胞色素水平的实质性降低。另外,NADH-和NADPH-氧化还原酶的活性水平降低,NADH-和NADPH-氧化还原酶是微粒体电子传输链成分的一部分,并与单氧合酶连接。这些变化证实了所研究的动物组织中的氧化还原状态以及脱毒和生物转化系统的功能活性受到干扰。我们较早开发的维生素D 3 补充剂和生物活性物质的组成有效地消除了免疫大鼠组织中细胞色素水平的降低和NADH氧化还原酶活性的降低。这些干扰的正常化可以通过所用物质的抗氧化剂和膜稳定特性来解释,也可以通过在EAE处通过调节大鼠生物体中炎症细胞因子的水平来降低炎症反应的活性来解释。因此,所研究的维生素-矿物质组合物似乎对于使发现的疾病正常化更为有效,并且对于预防加重以及改善多发性硬化症和其他疾病(伴有免疫系统过度活化)的患者的状况可能是有用的。

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