SEX DIFFERENCES IN PRO-ANTIOXIDANT SYSTEM INDICATORS IN MYOCARDIUM OF RATS UNDER THE CONDITIONS OF HYPERHOMOCYSTEINEMIA
DOI:
https://doi.org/10.11603/1811-2471.2017.v0.i1.7558Keywords:
hyperhomocysteinemia, hydrogen sulfide, oxidative stress, myocardium, sex.Abstract
Hyperhomocysteinemia is an independent risk factor of heart and blood vessels pathologies. One of the mechanisms of cardiotoxic action of homocysteine high concentrations is oxidative stress. In conditions of hyperhomocysteinemia in myocardium develops pro-antioxidant imbalance which is associated with exaggeration of the processes of free radical oxidation of lipids and proteins. However, sexual characteristics of hyperhomocysteinemia influence on the indicators of pro-antioxidant system in myocardium remain unknown.
The aim of the study is to evaluate the influence of hyperhomocysteinemia on indicators of oxidative stress in myocardium and the markers of cardiomyocytes cytolysis in males and female rats.
Materials and Methods. The experiments were performed on 40 white laboratory rats of both sexes weighing 220–280 g. The model of hyperhomocysteinemia was created by introducing of touchtone D, L-homocysteine (Sigma, USA) intraperitoneally at the dose of 100 mg/kg during 28 days. In myocardium, content of H2S, NADPH-oxidase activity, superoxide dismutase, content of malondialdehyde (MDA), protein carbonyl groups (CG) was determined. In blood serum, content of homocysteine, aspartatе aminotransferase activity (AST) and creatine phosphokinase (CPK) was evaluated. Statistical processing of the results was performed using the program Statistica SPSS 17.0.
Results and Discussion. Prolonged introduction to thiolactone homocysteine is accompanied by the increase of homocysteine in blood serum and reduce of hydrogen sulfide level in myocardium in males, respectively by 111 and 43.3 % (р<0,05), while in females – by 82.4 and 25.1 % (р<0.05), compared with the corresponding control group.
In males with hyperhomocysteinemia decrease in superoxide dismutase activity and increase of NADPH-oxidase activity, content of MDA and CG in myocardium were respectively 33.2; 52.7; 89.3 and 102 %, whereas in females the changes of these indicators were less and amounted to 23.7; 33.3; 68.3 and 78.6 %, relative to the control group.
In conditions of hyperhomocysteinemia, males develop more pronounced cytolysis of cardiomyocytes (activity of AST and CPK in serum increases, respectively, by 39.2 and 42.5 %, relative to the control group) than in females (levels of AST and CPK in serum increases by 24.9 and 31.3 %).
Conclusions. It is established that introduction of thiolactone homocysteine during 28 days causes in males a more significant decrease in superoxide dismutase activity and increased activity of NADPH-oxidase, processes of lipids and proteins peroxidation than in females. Along with this, the males recorded more pronounced cytolysis of cardiomyocytes than individuals of the opposite sex.
References
Loscalzo, J., & Handy, D.E. (2014). Epigenetic modifications: basic mechanisms and role in cardiovascular disease. Pulm. Circ. 4 (2), 169-174.
Lai, W.K., & Kan, M.Y. (2015). Homocysteine-Induced Endothelial Dysfunction. Ann. Nutr. Metab. 67 (1), 1-12.
Barna, O.M. (2007). Henderna kardiolohiia. Proektsiia na arytmii u zhinok [Gender cardiology. Projection on arrhythmias in women]. Meditsinskie aspekty zdorovia Zhenshchiny – Medical Aspects of Women's Health, 4 (7), 14-18 [in Ukrainian].
Regitz-Zagrosek, V., Oertelt-Prigione, S. & Seeland U. (2010). Sex and gender differences in myocardial hypertrophy and heart failure. Circ. J., 74 (7), 1265-1273.
Stangl, G.I., Weisse, K., & Dinger, C. (2007). Homocysteine thiolactone-induced hyperhomocysteinemia does not alter concentrations of cholesterol and SREBP-2 target gene mRNAS in rats. Exp. Biol. Med. (Maywood), 232, (1), 81-87.
Wiliński, B., Wiliński, J., & Somogyi, E. (2011). Carvedilol induces endogenous hydrogen sulfide tissue concentration changes in various mouse organs. Folia Biol (Krakow), 59 (3-4), 151-155.
Fukui, T., Ishizaka, N., & Rajagopalan, S. (1997). p22phox mRNA expression and NADPH oxidase activity are increased in aortas from hypertensive rats Circ. Res., 80, 45-51.
Kostiuk, V.A., Potapovich, A.I., & Kovaleva, Zh.V. (1990). Prostoi i chuvstvitelnyi metod opredeleniia aktivnosti superoksiddismutazy, osnovannyi na reaktsii okisleniia kvertsetina [А simple, sensitive assay for determination of superoxide dismutase activity based on reaction of quercetin oxidation]. Vopr. med. khimii – Problems of Medical Chemistry, 36 (2), 88-91 [in Russian].
Vladimirov Iu.V. & Archakov A.I. (1972). Perekisnoe okislenie lipidov v biologicheskikh membranakh [Lipid peroxidation in biological membranes]. Moscow: Nauka [in Russian].
Zaichko N.V. (2003). Okysliuvalna modyfikatsiia bilkiv syrovatky krovi yak marker aktyvnosti revmatoidnoho artrytu ta ii zminy pid vplyvom farmakoterapii amizonom, indometatsynom, nimesulidom [Oxidative modification of serum proteins as a marker of rheumatoid arthritis activity and its changes under the influence of pharmacotherapy amizon, indomethacin, nimesulide]. Visnyk Vinnytskoho derzhavnoho medychnoho universytetu – Journal of Vinnytsia State Medical University, 7 (2), 664-666 [in Ukrainian].
Kimura, Y., Goto, Y.I., Kimura, H. (2010). Hydrogen sulphide increases glutathione production and suppresses oxidative stress in mitochondria. Antioxidants and Redox Signaling, 12 (1), 1-13.
Miller, A.A., De Silva, T.M., Jackman, K.A., & Sobey C.G. (2007). Effect of gender and sex hormones on vascular oxidative stress. Clin. Exp. Pharmacol. Physiol., 34 (10), 1037-1043.
Bellanti, F., Matteo, M., & Rollo T. (2013). Sex hormones modulate circulating antioxidant enzymes: impact of estrogen therapy. Redox. Biol., 19 (1), 340-346.