CORM-2 AFFECTS LEVEL OF MALONDIALDEHYDE AND EXPRESSION OF MYOCARDIAL MARKERS PTGS2, ANP, BNP, MVH7 UNDER INDUCED FERROPTOSIS
DOI: 10.32999/ksu2524-0838/2022-32-5
Abstract
The formation of pro-oxidants in tissues is a dangerous phenomenon for the body. The emergence of pro-oxidants damages cell structures. Myocardium deserves special attention. This increases the level of superoxide radicals, hydrogen peroxide, and hydroxyl radicals under ischemia conditions. The formation of toxic active oxygen forms always accompanies ischemicreperfusion myocardial damage. The phenomenon of ferroptosis, which comprises the release of iron ions, increases lipid peroxidation to form malondialdehyde (MDA).
The endogenous formation of carbon monoxide, as a consequence of the breakdown of hemecontaining proteins, leads to increased expression of heme-oxygenase 1 (HO-1). It is an enzyme with antioxidant and anti-inflammatory properties. Substances that release carbon monoxide after exposure to physiological media are useful for research. Following ingestion, they decay slowly, releasing carbon monoxide. This gas transmitter may have a positive effect on the cells as ferroptosis develops. Doxorubicin (DOX) injected multiple times intraperitoneally into laboratory mice for ferroptosis induction. Every group of animals received additional hemin or HO-1 inhibitor (zinc-protoporphyrin), or donor CO – tricarbonyldichlorothenium (II)-dimer (CORM-2) in doses of 20 and 200 mg/kg. By the end of the experiment, the level of expression of the myocardial markers of Ptgs2 mRNA, Anp, Bnp, and Mvh7 was determined. Simultaneously, the myocardial homogenate determined the content of the MDA. As a result, the injection of CORM-2 at a concentration of 20 mg/kg found to reduce damage marker expression in the myocardium under conditions of ferroptosis induction. Same CORM-2 concentration also reduced the MDA content in the myocardium. Use of the HO-1 blocker had a positive effect on myocardial ferroptosis. The result showed that excessive activation of HO-1 has a negative effect on the heart. The influence of DOX and hemin on myocardium was negative, with increased expression of Ptgs2, Anp, Bnp, and Mvh7 markers. A high level of myocardial MDA accompanied the increased expression of these markers.
References
2. Beschasnyi SP, Hasiuk OM. The carbon monoxide donor, topiramate, and blockers of aquaporine receptors decrease myocardial ischemia-reperfusion injiry. Fiziologichnyi Zhurnal. 2021;67(5):30-38. https://doi.org/10.15407/fz67.05.030
3. Bloomer RJ, Cole B, Fisher-Wellman KH. Racial differences in postprandial oxidative stress with and without acute exercise. Int. J. Sport Nutr. and Exercise Metabol. 2009;19 (5): 457-472. DOI: https://doi.org/10.1123/ijsnem.19.5.457
4. Bonekamp NA, Völkl A, Fahimi HD, Schrader M. Reactive oxygen species and peroxisomes: struggling for balance. Biofactors. 2009;35(4):346-355. https://doi.org/10.1002/biof.48
5. Girotti AW. Lipid hydroperoxide generation, turnover, and effectors action in biological systems. J. Lipid. Res. 1998;39:1529-1542. DOI:https://doi.org/10.1016/S0022-2275(20)32182-9
6. Hasiuk OM, Samoilenko YuS, Polovynko TO, Leonenko SIu. Fizychna pratsezdatnist v umovakh vplyvu erytropoez-stymuliuiuchoho faktoru. Pryrodnychyi almanakh (biolohichni nauky). 2017;23:5-12. http://na.kspu.edu/index.php/na/article/view/621.
7. Henning B, Chow CK. Lipid peroxidation and endothelial cell in-jury: Implications in atherosclerosis. Free Radic. Biol. Med. 1988;4:9–100. https://doi.org/10.1016/0891-5849(88)90070-6
8. Kadaja L, Eimre M, Paju K, Roosimaa M, Põdramägi T, Kaasik P, Pehme A, Orlova E, Mudist M, Peet N, Piirsoo A, Seene T, Gellerich FN, Seppet EK. Impaired oxidative phosphorylation in overtrained rat myocardium. Exp. Clin. cardiol. 2010;15(4):116-127.
9. Longini M, Belvisi E, Proietti F, Bazzini F, Buonocore G, Perrone S: Oxidative stress biomarkers: establishment of reference values for isoprostanes, AOPP, and NPBI in cord blood. Mediators Inflamm 2017:1758432, 2017. https://doi.org/10.1155/2017/1758432
10. Otterbrien LE, Bach FH, Alam J. et al. Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway. Natur. Med. 2000;278(1):C92-C101. https://doi.org/10.1038/74680
11. Petrache I, Otterbein LE, Alam J. et al. Heme oxygenase-1 inhibits (TNF)-ά – indused apoptosis in cultured fibroblasts. Am. J. Phisiol. Lung Cell. Mol. Physiol. 2000;278:L312-L329. https://doi.org/10.1152/ajplung.2000.278.2.L312
12. Vallance P, Collier J, Moncada S. Effects of endothelium-derived nitric oxide on peripheral arterior tone in man. Lancet.1989; 2: 997-1000. https://doi.org/10.1016/S0140-6736(89)91013-1
13. Vanoverschelde JL, Wijns W, Depre C. et al. Mechanisms of chronic regional postischemic dysfunction in humans. New insights from the study of noninfarcted collateral-dependent myocardium. Circulation. 1993;87:1513-1523. https://doi.org/10.1161/01.CIR.87.5.1513
14. Wang R, Alam G, Zagariya A, et al. Apoptosis of lung epithelial cells in response to TNFalpha requires angiotensin II generation de novo. J. Cell. Physiol. 2000;185:253–259. https://doi.org/10.1002/1097-4652(200011)185:2<253::AID-JCP10>3.0.CO;2-%23
15. Yan HF, Tuo QZ, Yin QZ, Lei P. The pathological role of ferroptosis in ischemia/reperfusion-related injury. Zool Res. 2020;41(3):220-230. doi: 10.24272/j.issn.2095-8137.2020.042.
16. Кукоба Т. В., Мойбенко О.О. Гемоксигеназа та монооксид вуглецю: захист чи пошкодження клітин? Фізіол. Журнал. 2002;48(5):79-92.