Ukr.Biochem.J. 2018; Volume 90, Issue 4, Jul-Aug, pp. 36-44


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;
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.

Keywords: , , , , , , ,


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