Tag Archives: cytochrome b(5)
Liver cytochrome P450-hydroxylation system of tumor-bearing rats under the influence of ω-3 polyunsaturated fatty acids and vitamin D(3)
I. O. Shymanskyi1, O. V. Ketsa2, M. M. Marchenko2, М. М. Veliky1
1Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: ihorshym@gmail.com;
2Fedkovich Chernovtsy National University, Chernovtsy
The study was performed to investigate the effects of the separate and combined action of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) and vitamin D3 on the activity of the components of the oxygenase and reductase chains of the monooxygenase system (MOS) in the microsomal fraction isolated from the liver of rats with transplanted Guerin carcinoma. In the liver of the tumor-bearing rats during the intensive growth of the tumor (14 days, which corresponds to the logarithmic phase of tumor growth), the functional activity of the MOS was weakened. N-demethylase, p-hydroxylase and NADPH-cytochrome P450 reductase activity decreased, with the simultaneous enhancement of cytochrome P450 inactivation rate due to its transformation into an inactive form, cytochrome P420. In turn, we found an increase in the functional activity of the reductase chain of MOS, which components are known to transfer electrons from the reduced NADH through NADH-cytochrome b5-reductase and cytochrome b5 to cytochrome P450. In particular, the activity of NADH-cytochrome b5-reductase and the rate of reduction of cytochrome b5 were elevated with a simultaneous decrease in its content. Both ω-3 PUFAs and vitamin D3 administration to tumor-bearing rats for 42 days (28 days of preliminary administration and 14 days of tumor growth) significantly normalized the oxygenase activity of MOS, increasing NADPH-cytochrome P450-reductase, N-demethylase and p-hydroxylase activity of cytochrome P450 and blocking cytochrome P450 inactivation rate in the microsomal fraction of the liver. Administration of ω-3 PUFAs in combination with vitamin D3 led to the synergy. Changes in the activity of the components of the reductase chain of MOS in liver of tumor-bearing rats were observed mainly after ω-3 PUFAs supplementation. The content of cytochrome b5 increased and the rate of its reduction was significantly diminished. In the absence of a pronounced individual effect of vitamin D3 on the reductase chain of MOS, its co-administration with ω-3 PUFA was also found to be ineffective.
Monooxygenase system in Guerin’s carcinoma of rats under conditions of ω-3 polyunsaturated fatty acids administration
M. M. Marchenko, O. V. Ketsa, I. O. Shmarakov, K. H. Abutnaritsa
Fedkovich Chernovtsy National University, Ukraine;
e-mail: ketsa80@mail.ru
The aim of the study was to determine the variations of function in components of monooxygenase system (MOS) of rat Guerin’s carcinoma under ω-3 polyunsaturated fatty acids (PUFAs) administration. The activity of Guerin’s carcinoma microsomal NADH-cytochrome b5 reductase, the content and the rate of cytochrome b5 oxidation-reduction, the content and the rate of cytochrome Р450 oxidation-reduction have been investigated in rats with tumor under conditions of ω-3 PUFAs administration. ω-3 PUFAs supplementation before and after transplantation of Guerin’s carcinoma resulted in the increase of NADH-cytochrome b5 reductase activity and decrease of cytochrome b5 level in the Guerin’s carcinoma microsomal fraction in the logarithmic phases of carcinogenesis as compared to the tumor-bearing rats. Increased activity of NADH-cytochrome b5 reductase facilitates higher electron flow in redox-chain of MOS. Under decreased cytochrome b5 levels the electrons are transferred to oxygen, which leads to heightened generation of superoxide (O2•-) in comparison to control. It was shown, that the decrease of cytochrome P450 level in the Guerin’s carcinoma microsomal fraction in the logarithmic phases of oncogenesis under ω-3 PUFAs administration may be associated with its transition into an inactive form – cytochrome P420. This decrease in cytochrome P450 coincides with increased generation of superoxide by MOS oxygenase chain.
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.