Ukr.Biochem.J. 2013; Volume 85, Issue 5, Sep-Oct, pp. 137-148

doi: http://dx.doi.org/10.15407/ubj85.05.137

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

E. P. Pasichna1, G. V. Donchenko1, A. P. Burlaka2, V. S. Nedzvetskiy3,
E. P. Sidorik2, I. I.Ganusevich2, N. V. Delemenchuk1

1Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
2Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences of Ukraine, Kyiv;
3Honchar National University, Dnipropetrovsk, Ukraine;
e-mail: ellapasich@gmail.com

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 D3 and efficiency of its composition with vitamins B1, B2, B6, PP, E, α-lipoic, α-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.

Keywords: , , , , , , , , , , , , , ,


References:

  1. Lassmann H, Brück W, Lucchinetti CF. The immunopathology of multiple sclerosis: an overview. Brain Pathol. 2007 Apr;17(2):210-8. Review. PubMed, CrossRef
  2.  Mustafa M, Vingsbo C, Olsson T, Ljungdahl A, Höjeberg B, Holmdahl R. The major histocompatibility complex influences myelin basic protein 63-88-induced T cell cytokine profile and experimental autoimmune encephalomyelitis. Eur J Immunol. 1993 Dec;23(12):3089-95. PubMed, CrossRef
  3.  Schmitz T, Chew LJ. Cytokines and myelination in the central nervous system. Sci World J. 2008 Nov 2;8:1119-47. Review. PubMed, PubMedCentral, CrossRef
  4. Morgan ET. Regulation of cytochrome p450 by inflammatory mediators: why and how? Drug Metab Dispos. 2001 Mar;29(3):207-12. PubMed
  5. Okuno H, Takasu M, Kano H, Seki T, Shiozaki Y, Inoue K. Depression of drug-metabolizing activity in the human liver by interferon-beta. Hepatology. 1993 Jan;17(1):65-9. PubMed, CrossRef
  6.  Liakhovich VV, Vavilin VA, Zenkov NK, Menshikova EB. Reactive oxygen species during monooxygenase reactions.  Bull Siber Dep RAMS. 2005;118(4):7-12.
  7. Nadin L, Butler AM, Farrell GC, Murray M. Pretranslational down-regulation of cytochromes P450 2C11 and 3A2 in male rat liver by tumor necrosis factor alpha. Gastroenterology. 1995 Jul;109(1):198-205. PubMed, CrossRef
  8. Wright K, Morgan ET. Regulation of cytochrome P450IIC12 expression by interleukin-1 alpha, interleukin-6, and dexamethasone. Mol Pharmacol. 1991 Apr;39(4):468-74. PubMed
  9. Sibiryak SV. Cytokines as cytochrome P450-dependent monooxygenases regulators. Theoretical and applied aspects.  Cytokines Inflamm. 2003;2(2):12-22.
  10. Davydov DR. Microsomal monooxygenase in apoptosis: another target for cytochrome c signaling? Trends Biochem Sci. 2001 Mar;26(3):155-60. PubMedCrossRef
  11. Herrmann M, Scholmerich J, Straub RH. Influence of cytokines and growth factors on distinct steroidogenic enzymes in vitro: a short tabular data collection. Ann N Y Acad Sci. 2002 Jun;966(1):166-86. PubMedCrossRef
  12. Cantorna MT, Hayes CE, DeLuca HF. 1,25-Dihydroxyvitamin D3 reversibly blocks the progression of relapsing encephalomyelitis, a model of multiple sclerosis. Proc Natl Acad Sci USA. 1996 Jul 23;93(15):7861-4. PubMed, PubMedCentral, CrossRef
  13. Pasichna EP, Morozova RP, Donchenko HV, Chekhivs’ka LI. Redox-state of NAD pairs and activity of lactatedehydrogenase and NADase in guinea pig tissues at different stages of development of experimental allergic encephalomyelitis. Ukr Biokhim Zhurn. 2004 Nov-Dec;76(6):88-94. Ukrainian. PubMed
  14. Morozova RP, Pasichna EP, Donchenko GV, Kastrikina TF, Silonov SB, Palivoda OM, Delemenchuk NV. Lipids and caplain in guinea pigs tissues in the process of development of experimental autoimmune encephalomyelitis.  Ukr Biokhim Zhurn. 2007 Jan-Feb;79(1):104-11. PubMed
  15. Gibson GE, Zhang H. Interactions of oxidative stress with thiamine homeostasis promote neurodegeneration. Neurochem Int. 2002 May;40(6):493-504. PubMedCrossRef
  16. Johnson S. The possible role of gradual accumulation of copper, cadmium, lead and iron and gradual depletion of zinc, magnesium, selenium, vitamins B2, B6, D, and E and essential fatty acids in multiple sclerosis. Med Hypotheses. 2000 Sep;55(3):239-41. PubMedCrossRef
  17.  Pasichna EP, Donchenko GV, Delemenchuk NV, Burlaka AP. Functional state of mitochondria at experimental allergic encephalomyelitis and its vitamin correction.  Lab Diagnostics. 2012;61(3):23-30.
  18. Pasichna EP, Donchenko GV, Morozova RP. Effect of vitamin D3 and composition of vitamins on development of oxidative stress and lipid disbalance in brain tissues of rats at experimental autoimmune encephalomyelitis. Animal Biology. 2010;12(1):204-211.
  19. Burlaka AP, Sidorik YeP, Ganusevich II, Burlaka AA, Chulayevskaya OM, Shchepotin IB. Mitochondrial dysfunction and therapeutic strategies for regulation in patients with breast cancer. Neoplasm. Sci J Donetsk Regional Antitumor Centre. 2009;(3-4):247-253.
  20. Modern methods in biochemistry. Ed. V.N. Orekhovich. M.: Medicine, 1977; 392p.
  21.  Methods of biochemical research.  Ed. M. I. Prokhorova. L.: Publisher Leningrad University, 1982; 272p.
  22. Norton W. T., Cammer W. / Myelin. Plenum Press, N-Y., 1984. P. 147-195.
  23. Karlsson JO, Ostwald K, Kåbjörn C, Andersson M. A method for protein assay in Laemmli buffer. Anal Biochem. 1994 May 15;219(1):144-6. PubMedCrossRef
  24.   Peferoen M. Blotting with plate electrodes. Methods Mol Biol. 1988;3:395-402. PubMed, CrossRef
  25. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265-75. PubMed
  26. Lakin GF. Biometrics. Moscow: Vyshaya shkola, 1990;352p.
  27. Haining RL, Nichols-Haining M. Cytochrome P450-catalyzed pathways in human brain: metabolism meets pharmacology or old drugs with new mechanism of action? Pharmacol Ther. 2007 Mar;113(3):537-45. Review. PubMed, CrossRef
  28. Duan H, Luo Y, Hao H, Feng L, Zhang Y, Lu D, Xing S, Feng J, Yang D, Song L, Yan X. Soluble CD146 in cerebrospinal fluid of active multiple sclerosis. Neuroscience. 2013 Apr 3;235:16-26. PubMed, CrossRef
  29. Pasichna EP, Morozova RP, Donchenko HV, Vinychuk SM, Kopchak OO. Lipid peroxidation and antioxidant defence enzyme activity in multiple sclerosis. Ukr Biokhim Zhurn. 2007 Sep-Oct;79(5):165-74. Ukrainian. PubMed
  30. Garcion E, Wion-Barbot N, Montero-Menei CN, Berger F, Wion D. New clues about vitamin D functions in the nervous system. Trends Endocrinol Metab. 2002 Apr;13(3):100-5. Review. PubMed, CrossRef
  31. Garcion E, Sindji L, Leblondel G, Brachet P, Darcy F. 1,25-dihydroxyvitamin D3 regulates the synthesis of gamma-glutamyl transpeptidase and glutathione levels in rat primary astrocytes. J Neurochem. 1999 Aug;73(2):859-66. PubMedCrossRef
  32. Andersen HU, Jørgensen KH, Egeberg J, Mandrup-Poulsen T, Nerup J. Nicotinamide prevents interleukin-1 effects on accumulated insulin release and nitric oxide production in rat islets of Langerhans. Diabetes. 1994 Jun;43(6):770-7. PubMed, CrossRef
  33. Kim KA, Kim S, Chang I, Kim GS, Min YK, Lee MK, Kim KW, Lee MS. IFN gamma/TNF alpha synergism in MHC class II induction: effect of nicotinamide on MHC class II expression but not on islet-cell apoptosis. Diabetologia. 2002 Mar;45(3):385-93. PubMed, CrossRef
  34. Harrison FE, May JM. Vitamin C function in the brain: vital role of the ascorbate transporter SVCT2. Free Radic Biol Med. 2009 Mar 15;46(6):719-30. Review. PubMed, CrossRef
  35. Depeint F, Bruce WR, Shangari N, Mehta R, O’Brien PJ. Mitochondrial function and toxicity: role of the B vitamin family on mitochondrial energy metabolism. Chem Biol Interact. 2006 Oct 27;163(1-2):94-112. Review. PubMed, CrossRef
  36. Johnson S. The possible role of gradual accumulation of copper, cadmium, lead and iron and gradual depletion of zinc, magnesium, selenium, vitamins B2, B6, D, and E and essential fatty acids in multiple sclerosis. Med Hypotheses. 2000 Sep;55(3):239-41. PubMed, CrossRef
  37. Gibson GE, Zhang H. Interactions of oxidative stress with thiamine homeostasis promote neurodegeneration. Neurochem Int. 2002 May;40(6):493-504.  PubMed, CrossRef

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