EFFECT OF Ω-3 POLYUNSATURATED FATTY ACIDS ON THE FUNCTIONAL ACTIVITY OF MONOOXYGENASE SYSTEM IN THE LIVER MICROSOMAL FRACTION OF TUMOR-BEARING RATS
O.V. Ketsa, M.M. Marchenko, I.O. Shmarakov
Fedkovich Chernovtsy National University, Ukraine
The activity of liver components of monooxygenase system
(MOS) have been investigated in rats with tumor under
conditions of ω-3 polyunsaturated fatty acids (PUFAs) administration.
It was shown, that the intensive growth period
of Guerin’s carcinoma is thus associated with cytochrome
b5-reductase activity increased 2 times, and cytochrome b5
content decreased 2.8 times, and increased O2
rate in reductive chain of MOS in comparison to control. We
found NADPH-cytochrome P450-reductase activity decreased
2,4 times and cytochrome P450 content decreased 2,8 times in
oxygenative chain of MOS of rats with transplanted Guerin’s
carcinoma in the logarithmic phases of oncogenesis as compared
with the control. The decrease of cytochrome P450 level
in the liver microsomal fraction in the logarithmic phases of
oncogenesis may be associated with its transition into an inactive
form – cytochrome P420. ω-3 PUFAs (eicosapentaenoic
acid and docosahexaenoic acid) administration before and
after transplantation of Guerin’s carcinoma resulted in the
decrease of NADH-cytochrome b5-reductase activity, increase
of cytochrome b5 level, NADРH-cytochrome Р450 reductase
activity and cytochrome P450 level in the liver microsomal
fraction in the logarithmic phases of oncogenesis as compared
with the tumor-bearing rats. We have established the
correction of reductive and oxygenative chain of MOS under
ω-3 PUFAs administration prior Guerin’s carcinoma injection
as compared with the tumor-bearing rats. Yet the changes are
less pronounced than those of the group receiving ω-3 PUFAs
both prior to and post-Guerin’s carcinoma implantation. ω-3
PUFAs administration post-Guerin’s carcinoma injection
does not influence on activity of liver MOS components of
cytochrome P450; cytochrome b5; NADPH-cytochrome P450-reductase; NADH-cytochrome b5-reductase; ω-3 polyunsaturated fatty acids; microsomal fraction; liver, rats.
- Samedov VH, Naleskina LA, Zakharychev VD. Morphological changes during Geren carcinoma after cryoablation, a local microwave hyperthermia and their combination. Rus J Oncol. 2013; 3:17-21. [Russian].
- Lykashova OP. Influence of finaly fractional X-ray radiation in the total dose of 10 gy and etoposide chemotherapeutic agent on ultrastructure of Heren carcinoma cell. Ukr J Radiol. 2016; 24(1):14-21. [Ukrainian].
- Pettersen K, Monsen VT, Pettersen CH, Overland HB, Pettersen G, Samdal H, Tesfahun AN, Lundemo AG, Bjørkøy G, Schønberg SA. DHA-induced stress response in human colon cancer cells focus on oxidative stress and autophagy. Free Rad Biol Med. 2016; 90:158-72.
- Jeong S, Jing K, Kim N, Shin S, Kim S, Song K-S, Heo J-Y, Park J-H, Seo K-S, Han J, Wu T, Kweon G-R, Park S-K, Park J, Lim K. Docosahexaenoic acid-induced apoptosis is mediated by activation of mitogen-activated protein kinases in human cancer cells. BMC Cancer. 2014; 14:481-92.
- Fabian CJ, Kimler BF, Hursting SD. Omega-3 fatty acids for breast cancer prevention and survivorship. Breast Cancer Research. 2015; 17:62-73.
- Sharma A, Khan MAH, Levick SP, Lee KS, Hammock BD, Imig JD. Novel omega-3 fatty acid epoxygenase metabolite reduces kidney fibrosis. Int J Mol Sci. 2016; 17:751-62.
- Lopez-Vicario C, Alcaraz-Quiles J, Garcia-Alonso V, Rius B, Hwang SH, Titosc E, Lopategi A, Hammock BD, Arroyo V, Claria J. Inhibition of soluble epoxide hydrolase modulates inflammation and autophagy in obese adipose tissue and liver: role for omega-3 epoxides. PNAS. 2015; 112 (2):536-41.
- Porter TD. The roles of cytochrome b5 in cytochrome P450 reactions. J Biochem Mol Toxicol. 2002; 16:311-6.
- Park JW, Reed JR, Brignac-Huber LM, Backes WL. Cytochrome P450 system proteins reside in different regions of the endoplasmic reticulum. Biochem J. 2014; 464:241-9.
- Hamilton RL, Moorehouse A, Lear SR, Wong JS, Erickson SK. A rapid calcium precipitation method of recovering large amounts of highly pure hepatocyte rough endoplasmic reticulum. J. Lipid Res. 1999; 40:1140-7.
- Modern methods in biochemistry / ed. Orekhovich V.N. M. : Medicine, 1977; 386 p. [Russian]
- Mokhosoev IM, Kuznetsova GP, Alterman MA, Bachmanova GI, Archakov AI. Inactivation of cytochromes P-450 restored from sodium dithionite of various origin. Biochemistry. 1987; 52:1649-58. [Russian].
- Kostenko VO, Tsebrzhinskiy OI. Production of superoxide anion radical and nitric oxide in kidneys tissue sutured with different surgical suture materials. Fiziol Zh. 2000; 46(5):56-62. [Ukrainian].
- Lowry OH, Rosenbrough MJ, Farr AL, Rendal RJ. Rrotein measurement with the folin phenol reagent. J Biol Chem. 1951; 193:265-275.
- Brand MD, Affourtit C, Esteves TC, Green K, Lambert AJ, Miwa S, Pakay JL, Parker N. Mitochondrial superoxide: production, biological effects, and activation of uncoupling proteins. Free Radic Biol Med. 2004; 37:755-767.
- Davidson J, Rotondo D, Rizzo MT, Leaver HA. Therapeutic implications of disorders of cell death signalling: membranes, micro-environment, and eicosanoid and docosanoid metabolism. Br J Pharmacol. 2012; 166:1193-1210.
- Kovaleva VA, Shelest DV, Ostapchenko LI. The content of lipids and products of their peroxidation of rat thymocytes in experimental ulcerogenesis. Fiziol Zh. 2015;61(3):59-63. [Ukrainian].
- Ketsa OV, Shmarakov IO, Marchenko MM. Antioxidant system in liver and Guerin's carcinoma of rats under conditions of ω-3 polyunsaturated fatty acids administration. Biological systems. 2015;7(2): 177-183.
- Ketsa OV, Shmarakov IO, Marchenko MM, Aleksandrova AI. The induction of Guerin'scarcinoma free radical processes in mitochondrial fraction of rat by ω-3 polyusaturated fatty acids. Biopharm Journal. 2016; 8:30-5.
- Moreira JD, Hamraz M, Abolhassani M, Bigan E, Peres S, Pauleve L, Nogueira ML, Steyaert JM, Schwartz L. The redox status of cancer cells supports mechanisms behind the Warburg effect. Metabolites. 2016; 6 (4):33-45.
- Marchenko MM, Ketsa OV. Effect of liposomal antitumor preparation 5,6-benzcumarine-5-uracil on the free-radical processes intensity in the microsomal liver and tumor cells fraction of rats with transplanted Guerin's carcinoma. Ukr Biochem J. 2005; 77:141-6