Effects of edaravone on oxidative protein modification and activity of gelatinases after intracerebral hemorrhage in rats with nicotinamide-streptozotocin induced diabetes

Submitted: April 20, 2022
Accepted: December 4, 2022
Published: December 15, 2022
Abstract Views: 957
PDF: 313
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Authors

Stroke, especially hemorrhagic form, is one of the most serious comorbidity disease of Diabetes Mellitus (DM), often associated with high mortality, particularly in Type 2 DM (T2DM). Therefore, it is relevant the search for drugs with a metabolically justified protective effect. Edaravone (Eda) is widely used for treating ischemic stroke, but its biochemical effects in Intracerebral Hemorrhage (ICH) associated with T2DM are still not confirmed. The aim of the study was to assess the impact of Eda on the markers of Oxidative Modification of Proteins (OMP), such as Advanced Oxidation Protein Products (AOPP), neutral and basic carbonyls (PC370 and PC430), Advanced Glycation End products (AGEs) and Ischemia Modified Albumin (IMA) as well as on the activity of matrix metalloproteinases MMP2/MMP9 (gelatinases) in rats with experimental T2DM after collagenaseinduced ICH. Metformin was used as a comparative drug. The data obtained indicate that ICH in diabetic rats is accompanied by an increase in AOPP, PC370, AGEs, and mature forms of both gelatinases. On the contrary, IMA and proMMP9 were below normal level after ICH. Both studied drugs decreased the OMP markers to the levels of intact rats or lower, and Eda demonstrated a more potent effect. Besides, Eda decreased the activity of MMP9 and changed progelatinases activity. We conclude that Eda has a perspective to be useful in the treatment of comorbid brain hemorrhage in T2DM due to inhibition of oxidative stress and modulation of gelatinases activity.

Dimensions

Altmetric

PlumX Metrics

Downloads

Download data is not yet available.

Citations

World Health Organization (WHO), 2016. Global Report on Diabetes. Available from: https://www.who.int/publications/i/item/9789241565257
Hill MD. Stroke and diabetes mellitus. Handb Clin Neurol 2014;126:167-74. DOI: https://doi.org/10.1016/B978-0-444-53480-4.00012-6
Julia M, Santos D, Tewari S, Mendes RH. The role of oxidative stress in the development of diabetes mellitus and its complications. J Diabetes Res 2019;2019:4189813. DOI: https://doi.org/10.1155/2019/4189813
Infante-Garcia C, Garcia-Alloza M. Review of the effect of natural compounds and extracts on neurodegeneration in animal models of diabetes mellitus. Int J Mol Sci 2019;20:2533. DOI: https://doi.org/10.3390/ijms20102533
Hecker M, Wagner AH. Role of protein carbonylation in diabetes. J Inherit Metab Dis 2018;41:29-38. DOI: https://doi.org/10.1007/s10545-017-0104-9
Nair D, Nedungadi D, Mishra N, et al. Identification of carbonylated proteins from monocytic cells under diabetes-induced stress conditions. Biomed Chromatogr 2021;35:e5065. DOI: https://doi.org/10.1002/bmc.5065
Kay AM, Simpson CL, Stewart JA Jr. The Role of AGE/RAGE signaling in diabetes-mediated vascular calcification. J Diabetes Res 2016;2016:6809703. DOI: https://doi.org/10.1155/2016/6809703
Wang X, Khalil RA. Matrix Metalloproteinases, vascular remodeling, and vascular disease. Adv Pharmacol 2018;81:241-330. DOI: https://doi.org/10.1016/bs.apha.2017.08.002
Kostov K, Blazhev A. Use of glycated hemoglobin (A1c) as a biomarker for vascular risk in type 2 diabetes: its relationship with matrix metalloproteinases-2, -9 and the metabolism of collagen IV and Elastin. Medicina 2020;56:231. DOI: https://doi.org/10.3390/medicina56050231
Shakery T, Safari F. Down regulation of Pinkbar/pAKT and MMP2/MMP9 expression in MDA-MB-231 breast cancer cells as potential targets in cancer therapy by hAMSCs secretome. Cells Tissues Organs 2021. Available from: www.karger.com/Article/Abstract/520370 DOI: https://doi.org/10.1159/000520370
Shakkour Z, Issa H, Ismail H, et al. Drug repurposing: promises of edaravone target drug in traumatic brain injury. Curr Med Chem 2021;28:2369-91. DOI: https://doi.org/10.2174/1875533XMTA5tMDc5w
Potârniche AV, Dreancă AI, Sarpataki O, et al. Experimental model of streptozotocin-nicotinamide induced diabetes mellitus type II in sprague-dawley rats: step by step protocol and the encountered issues. Rev Rom Med Vet 2018;28:22-6.
Taylor EL, Armstrong KR, Perrett D, et al. Optimisation of an advanced oxidation protein products assay: its application to studies of oxidative stress in diabetes mellitus. Oxid Med Cell Longev 2015;2015:496271. DOI: https://doi.org/10.1155/2015/496271
Levine RL, Garland D, Oliver CN, et al. Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol 1990;186:464-78. DOI: https://doi.org/10.1016/0076-6879(90)86141-H
Tkachenko V, Kovalchuk Y, Bondarenko N, et al. The cardio-and neuroprotective effects of corvitin and 2-oxoglutarate in rats with pituitrin-isoproterenol-induced myocardial damage. Biochem Res Int 2018;2018:9302414. DOI: https://doi.org/10.1155/2018/9302414
Gaze DC. Biomarkers of cardiac ischemia. Ischemic Heart Disease Croatia In Tech Publishing. 2013. Available from: www.intechopen.com/chapters/42788
Toth M. Sohail A. Fridman R. Assessment of gelatinases (MMP-2 and MMP-9) by gelatinzymography. Methods Mol Biol 2012;878:121-35. DOI: https://doi.org/10.1007/978-1-61779-854-2_8
Lievykh АE, Tkachenko VA, Kharchenko YV, et al. Changes in biomarkers of endothelial function in the blood after intracerebral hemorrhage in rats with type 2 diabetes mellitus. Regul Mech Biosyst 2021;12:1-7. DOI: https://doi.org/10.15421/0221101
Zheng J, Chen X. Edaravone offers neuroprotection for acute diabetic stroke patients. Ir J Med Sci 2016;185:819-24. DOI: https://doi.org/10.1007/s11845-015-1371-9
Dzydzan O, Brodyak I, Sokół-Łętowska A, et al. Loganic acid, an iridoid glycoside extracted from cornus mas l. fruits, reduces of carbonyl/oxidative stress biomarkers in plasma and restores antioxidant balance in leukocytes of rats with streptozotocin-induced diabetes mellitus. Life 2020;10:349. DOI: https://doi.org/10.3390/life10120349
Dahiya K, Kumar R, Dhankhar R, et al. Status of ischemia modified albumin in athletes before and after moderate exercise. Open Biomark J 2018;8:42–6. DOI: https://doi.org/10.2174/1875318301808010042
Shevtsova A, Gordiienko I, Tkachenko V, Ushakova G. Ischemia-modified albumin: origins and clinical implications. Dis Markers 2021;2021:9945424. DOI: https://doi.org/10.1155/2021/9945424
Li W, Xu H, Hu Y, et al. Edaravone protected human brain microvascular endothelial cells from methylglyoxal-induced injury by inhibiting AGEs/RAGE/oxidative stress. PLoS One 2013;8:e76025. DOI: https://doi.org/10.1371/journal.pone.0076025
Lin С, Yang K, Zhang G, Yu J. Metformin ameliorates neuronal necroptosis after intracerebral hemorrhage by activating AMPK. Curr Neurovasc Res 2021;18:351-9. DOI: https://doi.org/10.2174/1567202618666210923150251
Rena G, Hardie DG, Pearson ER. The mechanisms of action of metformin. Diabetologia 2017;60:1577-85. DOI: https://doi.org/10.1007/s00125-017-4342-z
Castellazzi M, Tamborino C, De Santis G, et al. Timing of serum active MMP-9 and MMP-2 levels in acute and subacute phases after spontaneous intracerebral hemorrhage. Acta Neurochir Suppl 2010;106:137–40. DOI: https://doi.org/10.1007/978-3-211-98811-4_24
Lattanzi S, Di Napoli M, Ricci S, Divani AA. Matrix metalloproteinases in acute intracerebral hemorrhage. Neurotherapeutics 2020;17:484–96. DOI: https://doi.org/10.1007/s13311-020-00839-0
Miyamoto N, Pham LD, Maki T, et al. A radical scavenger edaravone inhibits matrix metalloproteinase-9 upregulation and blood-brain barrier breakdown in a mouse model of prolonged cerebral hypoperfusion. Neurosci Lett 2014;573:40-5. DOI: https://doi.org/10.1016/j.neulet.2014.05.005
Khokhar M, Roy D, Bajpai NK, et al. Metformin mediates microRNA-21 regulated circulating matrix metalloproteinase-9 in diabetic nephropathy: an in-silico and clinical study. Arch Physiol Biochem 2021;2021:1-11. DOI: https://doi.org/10.1080/13813455.2021.1922457
Zhao F, Liu Z. Beneficial effects of edaravone on the expression of serum matrix metalloproteinase-9 after cerebral hemorrhage. Neurosciences 2014;19:106-10.

How to Cite

Lievykh, A., Zhyliuk, V., Tkachenko, V., Kharchenko, Y., Ushakova, G., & Shevtsova, A. (2022). Effects of edaravone on oxidative protein modification and activity of gelatinases after intracerebral hemorrhage in rats with nicotinamide-streptozotocin induced diabetes. Journal of Biological Research - Bollettino Della Società Italiana Di Biologia Sperimentale, 95(2). https://doi.org/10.4081/jbr.2022.10554