The effects of gasotransmiters gasotransmitters inhibition on homocysteine thiolactone acutely induced changes in oxidative stress markers in rat plasm
Sažetak
AbstractBackground: The importance of homocysteine (Hcy) is increasingly recognized in last few decades as anindependent risk factor for atherosclerosis and thrombosis, but there is lack of data referring to influenceof Hcy on plasma oxidative stress parameters as well as the role of gasotransmitters in these effects.Therefore, this study aim was to assess the role of gasotransmitter inhibitors in Hcy-induced effects onplasma oxidative stress in rats.Material and Methods: Study involved 96 male Wistar albino rats divided into 8 groups: 1) Controlgroup – saline (1ml 0.9 % NaCl i.p.,); 2) DL-Hcy (8 mmol/kg i.p. DL homocysteine (DL-Hcy)); 3) L-NAME (10 mg/kg i.p. N ω -Nitro-L-arginine methyl ester (L-NAME), inhibitor of NO production); 4)ZnPPR IX (30 mol/kg i.p. protoporphyrin IX zinc (ZnPPR IX), inhibitor of CO production); 5) DL-PAG(50 mg//kg i.p. DL-propargylglycine (DL-PAG), inhibitor of H 2 S production); 6) DL-Hcy+L-NAME (8mmol/kgi.p. DL-Hcy + 10 mg/kg i.p. L-NAME); 7) DL-Hcy+ZnPPR IX (8 mmol/kgi.p. DL-Hcy + 30mol/kg i.p. Zn PPR IX), and 8) DL-Hcy+DL-PAG (8 mmol/kg i.p. DL-Hcy + 50 mg//kg i.p. DL-PAG).In all experimental groups, tested substances were administered in a single dose, intraperitoneally, 60minutes before animals’ euthanasia. In the collected blood samples malondialdehyde concentration,catalase, glutathione peroxidase and superoxide dismutase activity were measured.Results: Applied substances induced rapid and strong increase of plasma antioxidant enzymatic activityprobably as a compensatory response to its pro-oxidant influence.Conclusion: The effects of Hcy on the activity of plasma antioxidant enzymes are in part mediated viainteraction with gasotransmitters.
Reference
Strain JJ, Dowey L, Ward M, Pentieva K, McNulty H. B-vitamins, homocysteine metabolism and CVD. Proc Nutr Soc 2004;63(4):597-603.
Schaffer A, Verdoia M, Cassetti E, Marino P, Suryapranata H, De Luca G. Novara Atherosclerosis Study Group (NAS). Relationship between homocysteine and coronary artery disease. Results from a large prospective cohort study. Thromb Res 2014;134(2):288-93.
Mujumdar VS, Tummalapalli CM, Aru GM, Tyagi SC. Mechanism of constrictive remodeling by homocysteine: role of PPAR. Am J Physiol Cell Physiol 2002;282:C1109–15.
Ungvari Z, Csiszar A, Edwards JG, et al. Increased superoxide production in coronary arteries in hyperhomocysteinemia. Role of tumor necrosis factor-α, NAD(P)H oxidase, and inducible nitric oxide synthase. Arterioscler Thromb Vasc Biol 2003;23:418–23.
Derouiche F, Bôle-Feysot C, Naïmi D, Coëffier M. Hyperhomocysteinemia-induced oxidative stress differentially alters proteasome composition and activities in heart and aorta. Biochem Biophys Res Commun 2014;452(3):740-5.
Liu HH, Shih TS, Huang HR, Huang SC, Lee LH, Huang YC. Plasma homocysteine is associated with increased oxidative stress and antioxidant enzyme activity in welders. Sci World J 2013; e370487.
Gimenes R, Gimenes C, Rosa C.M, et al. Influence of apocynin on cardiac remodeling in rats with streptozotocin-induced diabetes mellitus. Cardiovasc Diabetol 2018; 17(1):15. doi: 10.1186/s12933-017-0657-9.
da Cunha AA, Scherer E, da Cunha MJ, et al. Acute hyperhomocysteinemia alters the coagulation system and oxidative status in the blood of rats. Mol Cell Biochem 2012;360(1-2):205-14.
Kerkeni M, Added F, Ben Farhat M, Miled A, Trivin F, Maaroufi K. Hyperhomocysteinaemia and parameters of antioxidative defence in Tunisian patients with coronary heart disease. Ann Clin Biochem 2008;45(2):193-8.
Wilcken DE, Wang XL, Adachi T, et al. Relationship between homocysteine and superoxide dismutase in homocystinuria: possible relevance to cardiovascular risk. Arterioscler Thromb Vasc Biol 2000;20(5):1199-202.
Matté C, Mackedanz V, Stefanello FM, et al. Chronic hyperhomocysteinemia alters antioxidant defenses and increases DNA damage in brain and blood of rats: protective effect of folic acid. Neurochem Int 2009;54(1):7-13.
Wang R, editor. Signal transduction and the gasotransmitters: NO, CO and H2S in biology and medicine. Humana Press, New Jersey, USA, 2004.
Zivkovic V, Jakovljevic V, Pechanova O, et al. Effects of DL-homocysteine thiolactone on cardiac contractility, coronary flow, and oxidative stress markers in the isolated rat heart: the role of different gasotransmitters. Biomed Res Int 2013; 2013:318471.
Aruoma OI, Halliwell B, Laughton MJ, Quinlan GJ, Gutteridge JMC. The mechanism of initiation of lipid peroxidation. Evidence against a requirement for an iron (II)- iron (III) complex. Biochemical Journal 1989;258:617–20.
Stamler JS, Osborne JA, Jaraki O, Rabbani LE, Mullins M, Singel D, et al. Adverse vascular effects of homocysteine are modulated by endothelium-derived relaxing factor and related oxides of nitrogen. J Clin Invest 1993;91:308–18.
Xu S, Liu Z, Liu P. Targeting hydrogen sulfide as a promising therapeutic strategy for atherosclerosis. Int J Cardiol 2014;172:313–17.
Kabil O, Motl N, Banerjee R. H2S and its role in redox signaling. Biochim Biophys Acta 2014;1844:1355–66.
Cebova M, Košutova M, Pechanova O. Cardiovascular Effects of Gasotransmitter Donors Physiol Res 2016;65 (Suppl. 3): S291-S307.
Beutler E. Catalase. In: Red cell metabolism, a manual of biochemical methods. E Beutler, editors. New York: Grune and Stratton; 1982, p. 105-6.
Misra HP, Fridovich I. The role of superoxide-anion in the autooxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 1972; 247: 3170-5.
Vives-Bauza C, Starkov A, Garcia-Arumi E. Measurements of the antioxidant enzyme activities of superoxide dismutase, catalase, and glutathione peroxidase. Methods Cell Biol 2007; 80:379-93.
Boyacioglu M, Sekkin S, Kum C, et al. The protective effects of vitamin C on the DNA damage, antioxidant defenses and aorta histopathology in chronic hyperhomocysteinemia induced rats. Exp Toxicol Pathol 2014; 66(9-10):407-13.
Kwiecien S, Jasnos K, Magierowski M, et al. Lipid peroxidation, reactive oxygen species and antioxidative factors in the pathogenesis of gastric mucosal lesions and mechanism of protection against oxidative stress – induced gastric injury. J Physiol Pharmacol 2014; 65(5):613-22.
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).