[Use of vitamins for correction of the functional state of cytochrome P450 systems in experimental allergic encephalomyelitis].

It is known that inflammatory cytokines, which level is significantly increased in the pathogenesis of multiple sclerosis (MS), as well as interferon-beta, 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 D3 and efficiency of its composition with vitamins B1, B2, B6, PP, E, alpha-lipoic, alpha-linolenoic acid and mineral substances (Mg, Zn, Se) in prevention of a functional state changes of cytochrome P450- and b5-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 D3 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.

[Effects of alpha-tocopherol and its anologues on rat thymocytes programmed death induced by protein kinase inhibitors].

It is established that alpha-tocopherol (alpha-TPh) shows cytoprotective effect at the induction of rats' thymocytes apoptosis by endocellular protein kinase inhibitors--staurosporine and phorbol ether in high concentration, and also on necrosis of the cells caused by sphyngosine. The effect of alpha-TPh on thymocytes death caused by protein phosphatase type 2A inhibitor ocadaic acid is much less expressed. The obtained data testify that the known ability of alpha-TPh to the inhibition of PKC and to the activation of protein phosphatase type 2A is not the main mechanism of its cytoprotective action. Partial reproduction of alpha-TPh effects by its analogue alpha-tocopheryl acetate which is not capable to enter in redox reactions, and the absence of influence on the studied processes of an antioxidant of N-acetyl-L-cysteine do not confirm the antioxidant mechanism of alpha-TPh action in this case. The inhibition by alpha-TPh of the release of cytochrome c in the cytosol of cells testifies to the implementation of its cytoprotective effect at the level of mitochondrial membranes. We assume the existence of the universal mechanism of alpha-TPh cytoprotective action that does not depend on the nature of apoptogenes and realized on the general for the majority of them stage of the cells death induction. The prevention by alpha-TPh of mitochondria dysfunction by stabilizing mitochondrial membranes and reduction of their permeabilization is supposed as that.

[Lipids and caplain in guinea pig tissues in the process of development of experimental autoimmune encephalomyelitis].

The character of some lipids level change--cholesterol and phospholipids--as basic lipid components of cell membranes in the guinea-pig brain and liver tissue, and in serum in conditions of development of experimental autoimmune encephalomyelitis (EAE) have been investigated on the 11th, 21st, 27th day after inoculation. It has been detected, that the level of the investigated lipids changes wavely and indifferent-direction in the brain tissue on the 21st day of EAE. Similar variability observed in the activity of proteolytic ferment calpain, which is authentically reduced in the brain tissue by the 11th hour and increases up to the test objective level in the subsequent periods of EAE development. In the liver the level of alpha-tocopherol is reduced, while the content of studied lipids does not change. The investigated parameters can be attributed to the factors, which play an essential role in structural stability of cell membranes and their variability in conditions of EAE development is related to the processes of nervous cells demyelinisation and, hence to occurrence of such pathology as multiple sclerosis in people.