Introduction. Acute disorders of cerebral circulation similar to diabetes mellitus (DM) cause long-term multiple organ effects, although pathogenesis of internal organs injury in association with DM and cerebral ischemia-reperfusion has not been investigated completely.  

The aim of the study. To study the dynamics of the content of protein oxidative modification and metabolites in the myocardium and kidneys of rats with DM complicated by cerebral ischemia-reperfusion.  

Results. The content of protein oxidative modification products in the tissues of the kidneys and myocardium and the content of nitrogen monoxide metabolites in the cortical and medullary substance of the kidneys were found to decrease in the early ischemic-reperfusion period in rats without DM. In rats with DM early post-ischemic changes are restricted by the increase of nitrogen oxide metabolites content in the renal medullary substance. Total remote changes of the examined parameters are found in the myocardium of rats without DM and the medullary substance of the kidneys in rats with DM.   

Conclusions. Diabetes mellitus eliminates or restricts the reaction of the examined indices peculiar for control animals in both periods of observation in all the examined tissues except the medullary substance of the kidneys on the 12th day of the post-ischemic period

M. A. Povar

O. V. Tkachuk

O. V. Yasinska

S. S. Tkachuk

S. V. Boshtan

T. P. Savchuk

V. F. Myslytskyi

V. P. Gavaleshko

Journal of Education Health and Sport

Tkachuk О. V., Tkachuk S. S., Myslytskyi V. F., Gavaleshko V. P., Yasinska O. V., Povar M. A., Boshtan S. V., Savchuk T. P. Content of protein oxidative modification products and nitrogen monoxide metabolites in the kidneys and myocardium of rats with streptozotocin-induced diabetes in dynamics of cerebral ischemia-reperfusion. Journal of Education, Health and Sport. 2018;8(7):545-550. eISNN 2391-8306. DOI http://dx.doi.org/10.5281/zenodo.1344631

http://ojs.ukw.edu.pl/index.php/johs/article/view/5804

 

 

 

 

 The journal has had 7 points in Ministry of Science and Higher Education parametric evaluation. Part b item 1223 (26/01/2017).

1223 Journal of Education, Health and Sport eissn 2391-8306 7 ©

 

The Authors 2018; This article is published with open access at Licensee Open Journal Systems of Kazimierz Wielki University in Bydgoszcz, Poland

 Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium,

provided the original author (s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non commercial license Share alike.

 (http://creativecommons.org/licenses/by-nc-sa/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited.

 

The authors declare that there is no conflict of interests regarding the publication of this paper.

 

Received: 25.06.2018. Revised: 30.06.2018. Accepted: 31.07.2018.

 

 

CONTENT OF PROTEIN OXIDATIVE MODIFICATION PRODUCTS AND NITROGEN MONOXIDE METABOLITES IN THE KIDNEYS AND MYOCARDIUM OF RATS WITH STREPTOZOTOCIN-INDUCED DIABETES IN DYNAMICS OF CEREBRAL ISCHEMIA-REPERFUSION

 

О. V. Tkachuk, S. S. Tkachuk, V. F. Myslytskyi, V. P. Gavaleshko,

O. V. Yasinska, M. A. Povar, S. V. Boshtan, T. P. Savchuk

 

Higher State Educational Establishment of Ukraine

“Bukovinian State Medical University”, Chernivtsi, Ukraine

 

Abstract

Introduction. Acute disorders of cerebral circulation similar to diabetes mellitus (DM) cause long-term multiple organ effects, although pathogenesis of internal organs injury in association with DM and cerebral ischemia-reperfusion has not been investigated completely.

The aim of the study. To study the dynamics of the content of protein oxidative modification and metabolites in the myocardium and kidneys of rats with DM complicated by cerebral ischemia-reperfusion.

Results. The content of protein oxidative modification products in the tissues of the kidneys and myocardium and the content of nitrogen monoxide metabolites in the cortical and medullary substance of the kidneys were found to decrease in the early ischemic-reperfusion period in rats without DM. In rats with DM early post-ischemic changes are restricted by the increase of nitrogen oxide metabolites content in the renal medullary substance. Total remote changes of the examined parameters are found in the myocardium of rats without DM and the medullary substance of the kidneys in rats with DM.

Conclusions. Diabetes mellitus eliminates or restricts the reaction of the examined indices peculiar for control animals in both periods of observation in all the examined tissues except the medullary substance of the kidneys on the 12th day of the post-ischemic period.

Key words: diabetes mellitus, nephropathy, cardiomyopathy, cerebral ischemia-reperfusion

Tkachuk, О. V.

Tkachuk, S. S.

Myslytskyi, V. F.

Gavaleshko, V. P.

Yasinska, O. V.

Povar, M. A.

Boshtan, S. V.

Savchuk, T. P.

NEUROSURGERY ENTHUSIASTIC WOMEN SOCIETY

Content of protein oxidative modification products and nitrogen monoxide metabolites in the kidneys and myocardium of rats with streptozotocin-induced diabetes in dynamics of cerebral ischemia-reperfusion

Directory of Open Access Journals

  545 Tkachuk О. V., Tkachuk S. S., Myslytskyi V. F., Gavaleshko V. P., Yasinska O. V., Povar M. A., Boshtan S. V., Savchuk T. P. Content of protein oxidative modification products and nitrogen monoxide metabolites in the kidneys and myocardium of rats with streptozotocin-induced diabetes in dynamics of cerebral ischemia-reperfusion. Journal of Education, Health and Sport. 2018;8(7):545-550. eISNN 2391-8306. DOI http://dx.doi.org/10.5281/zenodo.1344631  http://ojs.ukw.edu.pl/index.php/johs/article/view/5804      The journal has had 7 points in Ministry of Science and Higher Education parametric evaluation. Part b item 1223 (26/01/2017).  1223 Journal of Education, Health and Sport eissn 2391-8306 7 ©   The Authors 2018; This article is published with open access at Licensee Open Journal Systems of Kazimierz Wielki University in Bydgoszcz, Poland  Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author (s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non commercial license Share alike.  (http://creativecommons.org/licenses/by-nc-sa/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited.   The authors declare that there is no conflict of interests regarding the publication of this paper.   Received: 25.06.2018. Revised: 30.06.2018. Accepted: 31.07.2018.   CONTENT OF PROTEIN OXIDATIVE MODIFICATION PRODUCTS AND NITROGEN MONOXIDE METABOLITES IN THE KIDNEYS AND MYOCARDIUM OF RATS WITH STREPTOZOTOCIN-INDUCED DIABETES IN DYNAMICS OF CEREBRAL ISCHEMIA-REPERFUSION   О. V. Tkachuk, S. S. Tkachuk, V. F. Myslytskyi, V. P. Gavaleshko,  O. V. Yasinska, M. A. Povar, S. V. Boshtan, T. P. Savchuk  Higher State Educational Establishment of Ukraine “Bukovinian State Medical University”, Chernivtsi, Ukraine  Abstract  Introduction. Acute disorders of cerebral circulation similar to diabetes mellitus (DM) cause long-term multiple organ effects, although pathogenesis of internal organs injury in association with DM and cerebral ischemia-reperfusion has not been investigated completely. The aim of the study. To study the dynamics of the content of protein oxidative modification and metabolites in the myocardium and kidneys of rats with DM complicated by cerebral ischemia-reperfusion. Results. The content of protein oxidative modification products in the tissues of the kidneys and myocardium and the content of nitrogen monoxide metabolites in the cortical and medullary substance of the kidneys were found to decrease in the early ischemic-reperfusion period in rats without DM. In rats with DM early post-ischemic changes are restricted by the increase of nitrogen oxide metabolites content in the renal medullary substance. Total remote changes of the examined parameters are found in the myocardium of rats without DM and the   546 medullary substance of the kidneys in rats with DM. Conclusions. Diabetes mellitus eliminates or restricts the reaction of the examined indices peculiar for control animals in both periods of observation in all the examined tissues except the medullary substance of the kidneys on the 12th day of the post-ischemic period. Key words: diabetes mellitus, nephropathy, cardiomyopathy, cerebral ischemia-reperfusion.  The main causes of disability and mortality of patients suffering from diabetes mellitus (DM) are its complications including cardiomyopathy and nephropathy [1-4]. Recognized links of their pathogenesis are accumulation of sorbitol in the tissues, activation of non-enzymatic glycated proteins, oxidative stress, endothelial dysfunction etc. [5-8]. Meanwhile accumulation of data concerning the mechanisms injuring the internal organs in patients suffering from DM is not sufficient to prevent the development of complications. Deficiency of scientific studies of internal organs pathology associated with DM and acute disorders of cerebral circulation is especially significant, since both the latter and DM are know to provoke long-term multiple organ effects [9, 10]. Moreover, close interrelations are found to occur between disorders of the coronary and cerebral circulation [11-12], and chronic renal pathology and diabetes are predictors of higher mortality in patients suffering from cardiovascular pathology [13, 14]. Objective and tasks: to investigate the content of protein oxidative modification products and nitrogen monoxide metabolites in the myocardium and kidneys of rats with DM complicated by incomplete global cerebral ischemia-reperfusion.    Materials and methods of the study. Type 1 diabetes mellitus was simulated by means of streptozotocin (Sigma, USA, 60 mg / kg of the body weight) introduced intra-peritoneally into albino male rats aged two months [15]. Bilateral carotid ischemia-reperfusion by means of clipping of both major carotid arteries during 20 minutes was modeled four months later in a part of animals with DM and six-months control rats [16]. To study early consequences of ischemia-reperfusion a part of the animals were taken out from the experiment one hour later since the onset of reperfusion, and the rest – on the 12th day. The content of protein oxidative modification (POM) products of a neutral and basic character, and nitrogen oxide metabolites in homogenates of the cortical and medullary substances of the kidneys and myocardium were examined [17] with the use of reagents produced by Simko Ltd, Ukraine. Surgery and euthanasia were performed under calipsol narcosis (70 mg/kg of the body weight). The data obtained were processed by means of the   547 packet of applied programs “Statistica (“Statsoft”, USA). Statistical significance of differences was assessed by Student t-criterion for independent sampling.  Results and discussion. The analysis of the results obtained draws special attention to considerable lower constitutional parameters of POM products content and nitrogen monoxide metabolites in the medullary substance of the kidneys compared with the cortical one both in the control animals and those with simulated DM (Table 1). Table 1 Effect of cerebral ischemia-reperfusion on the content of protein oxidative modification products and nitrogen monoxide metabolites in the kidneys of rats with diabetes mellitus   (М±m, n=11) Group of observation Content of aldehyde- and ketone derivatives Content of nitrogen oxide metabolites Neutral character (o.d.u./g of protein, 370 nm) Basic character (о.d.u./g of protein,  420 nm) Cortical substance Control  45,27±0,85 21,49±0,47 75,11±0,62 Cerebral ischemia-reperfusion (20 min/ 1 hour) 41,00±0,43  19,14±0,37 р0,002 69,56±0,77 р0,001 Cerebral ischemia-reperfusion (12 days) 45,24±1,03 р10,001 20,98±0,50 74,54±0,74 р10,001 Diabetes  46,65±0,94 22,46±0,39 75,17±0,47 Diabetes and cerebral ischemia-reperfusion (20 min/1 hour) 46,86±0,56 21,99±0,44 78,67±1,74 Diabetes and cerebral ischemia-reperfusion (12 days) 45,64±0,56 20,72±0,38 75,85±0,51 Medullary substance Control  25,99±0,42 12,54±0,28 48,51±0,72 Cerebral ischemia-reperfusion (20 min/ 1 hour) 22,77±0,44 р0,001 10,38±0,50  р0,002 44,57±0,86 р0,004 Cerebral ischemia-reperfusion (12 days) 26,44±0,63   р10,001 20,02±1,79 р0,005 р10,001 50,41±0,99   р10,001 Diabetes  26,76±0,44 12,97±0,36 46,14±0,62 р0,025 Diabetes and cerebral ischemia-reperfusion (20 min/1 hour) 26,76±0,31 13,06±0,32 49,73±0,90 р20,01 Diabetes and cerebral ischemia-reperfusion (12 days) 28,41±0,40 р20,05 р30,05 14,40±0,24 р20,01  р30,01 41,83±0,77 р20,001  р30,05 Notes: 2: – probability of difference compared with: р - control; р1 – ischemia-reperfusion (20 min / 1 hour) in animals from the control group; р2 – diabetes; р3 – ischemia-reperfusion (20 min / 1 hour) in animals with diabetes; o.d.u. – optical density units.   548 Ischemia with one-hour reperfusion in animals with DM caused reliable decrease of POM products of a neutral and basic character and nitrogen monoxide metabolites in the cortical and medullary substances of the kidneys respectively. On the 12th day of ischemic-reperfusion period reliable changes of the above indices were not found in the cortical substance, and in the medullary substance the content of POM products of a basic character increased. The examined indices were not changed in the cortical substance of the kidneys of rats with DM either complicated or not complicated by cerebral ischemia-reperfusion. In the medullary substance DM decreased reliably the content of nitrogen monoxide metabolites compared with the index of the control group. In the early period of cerebral ischemia-reperfusion the content of nitrogen monoxide metabolites in this portion of the kidneys increased, and on the 12th day – decreased concerning the indices associated with diabetes. Characteristics of the examined indices in the myocardium of the experimental animals is presented in Table 2. Table 2 Effect of cerebral ischemia-reperfusion on the content of protein oxidative modification products and nitrogen monoxide metabolites in the myocardium of rats with diabetes mellitus   (М±m, n=11) Group of eobservation Content of aldehyde- and ketone derivatives Nitrogen oxide content Neutral character (o.d.u./g of protein, 370 nm) Basic character (о.d.u./g of protein,  420 nm) Control  43,66±0,27 21,19±0,21 74,10±1,36 Cerebral ischemia-reperfusion (20 min/ 1 hour) 41,00±0,43 р0,001 19,14±0,37 р0,004 75,78±2,79  Cerebral ischemia-reperfusion (12 days) 48,75±0,30  р0,001 22,21±0,37  р0,01 100,87±2,08 р0,001 Diabetes 46,61±0,56 р0,001 21,43±0,28 84,63±1,63 р0,001 Diabetes and cerebral ischemia-reperfusion (20 min/1 hour) 46,18±0,58   21,74±0,20 83,99±0,86 Diabetes and cerebral ischemia-reperfusion (12 days) 45,88±0,23 21,40±0,27 90,14±0,91 р20,007  At the end of early post-ischemic period the content of POM products of a neutral and basic character decreased reliably in the myocardium of rats without DM, but on the 12th day   549 it increased. Moreover, the content of nitrogen monoxide metabolites increased considerable as well. A reliable increase of POM products of a neutral character and nitrogen monoxide metabolites was found in the myocardium of rats with DM. In animals with DM complicated by cerebral ischemia-reperfusion compared with uncomplicated diabetes there were no reliable changes found concerning the examined indices after one-hour reperfusion, and reliable increase of the content of nitrogen monoxide metabolites was detected on the 12th day of the experiment. The results obtained are indicative of available organ-specific changes of the intensity of POM processes and formation of nitrogen monoxide metabolites in the kidneys and myocardium of both control animals and those with DM. Conclusions. Diabetes mellitus eliminates or restricts the reaction of the examined indices peculiar for the control animals in both terms of observation in all the examined tissues, except the medullary substance of the kidneys on the 12th day of post-ischemic period. References 1. Aneja A., Tang W.H., Bansilal S., Garcia M.J., Farkouh M.E. Diabetic cardiomyopathy: insights into pathogenesis, diagnostic challenges, and therapeutic options. Am. J. Med. .2008; 121(9):748-57.  2. Ernande L., Derumeaux G. Diabetic cardiomyopathy: myth or reality? Arch. Cardiovasc. Dis. 2012; 105(4): 218-25.  3. Stevens L.A., Li S., Kurella Tamura M., Chen S.C., Vassalotti J.A., Norris K.C., Whaley-Connell A.T., Bakris G.L., McCullough P.A.Sowers Сomparison of the CKD epidemiology collaboration (C KD-EPI) and modification of diet in renal disease (MDRD) study equations: prevalence of and risk Factors for Diabetes Mellitu s in CKD in the Kidney Early Evaluation Program (KEEP). Am. J. Kidney Dis. 2011; 57(Is.3, Suppl. 2): 24-31.  4. Shao D., Liu J., Ni J., Wang Z., Shen Y., Zhou L., et al. Suppression of XBP1S Mediates High Glucose-Induced Oxidative Stress and Extracellular Matrix Synthesis in Renal Mesangial Cell and Kidney of Diabetic Rats. PLoS One. 2013; 8(2): e56124.  5. Boghdady N.A., Bard G.A. Evaluation of oxidative stress markers and vascular risk factors in patients with diabetic peripheral neuropathy. Cell. Biochem. Funct. 2012; 30(4): 328–34. 6. Mild oxidative damage in the diabetic rat heart is attenuated by glyoxalase-1 overexpression / O. Brouwers, J.M. de Vos-Houben, P.M. Niessen [et al.] // Int. J. Mol. Sci. – 2013. – Vol.14, №8. – Р. 15724-15739.   550 7. Falcão-Pires I., A.F. Leite-Moreira. Diabetic cardiomyopathy: understanding the molecular and cellular basis to progress in diagnosis and treatment. Heart Fail. Rev. 2012; 17(3): 325-44. 8. Sedeek M., Callera G., Montezano A. Critical role of Nox4-based NADPH oxidase in glucose-induced oxidative stress in the kidney: implications in type 2 diabetic nephropathy. Am. J. Physiol. Renal Physiol. 2010; 299(№6): 1348-58. 9. Muscari A., Collini A., Fabbri E., Giovagnoli M., Napoli C., Rossi V., et al. Changes of liver enzymes and bilirubin during ischemic stroke: mechanisms and possible significance. BMC Neurol. 2014;14(122). doi: 10.1186/1471-2377-14-122. 10. Chiu N.L., Kaiser B., Nguyen Y.V., Welbourne S., Lall C., Cramer S.C. The Volume of the Spleen and its Correlates after Acute Stroke. J. Stroke Cerebrovasc. Dis. 2016; 25(12): 2958–61. 11. Hassan Y., Aziz N.A., Al-Jabi S.W., Looi I. Evaluation of antihypertensive therapy among ischemic stroke survivors: impact of ischemic heart disease. J. Cardiovasc. Pharmacol. Ther. 20104; 15(3): 282-88. 12. Banerjee A., Lim C.C., Silver L.E., Welch S.J. Familial history of stroke is associated with acute coronary syndromes in women. Circ. Cardiovasc. Genet. 2011; 4(1). Р.9-15.  13. Rashidi A., Sehgal A.R., Rahman M., O'Connor A.S. The case for chronic kidney disease, diabetes mellitus, and myocardial infarction being equivalent risk factors for cardiovascular mortality in patients older than 65 years. Am. J. Cardiol. 2008; 102(12): 1668-73.  14. Cianciolo G., De Pascalis A., Di Lullo L., Ronco C., Zannini C., La Manna G. Folic Acid and Homocysteine in Chronic Kidney Disease and Cardiovascular Disease Progression: Which Comes First? Cardiorenal. Med. 2017; 7(4): 255–66.  15. Tkachuk, S.S., Lenkov, A.M. Ekspresiia bilkiv Hif-1α, р53 ta Bcl-2 v golovnomu mozku za umov dvobichnoi karotidnoi ishemii-reperfuzii na tli tsukrovogo diabetu v samtsiv-shchuriv. Klinichna ta eksperimentalna patologiia. 2010; 2(32): 111–113. 16. Skibo G.G. Ispolzovanie razlichnikh eksperimentalnikh modelei dlia izucheniia kletochnikh mechanizmov іshemicheskogo porazheniia mozga. Patologija. 2004; 1(1): 22-30. 17. Mahalyas VM, Mikhyeyev AO, Rohovyy YuYe. Suchasni metody eksperymental'nykh ta klinichnykh doslidzhen' tsentral'noyi naukovo-doslidnoyi laboratoriyi Bukovyns'koyi derzhavnoyi medychnoyi akademiyi. Chernivtsi; 2001. 42 s. 

Introduction. Acute disorders of cerebral circulation similar to diabetes mellitus (DM) cause long-term multiple organ effects, although pathogenesis of internal organs injury in association with DM and cerebral ischemia-reperfusion has not been investigated completely.  
The aim of the study. To study the dynamics of the content of protein oxidative modification and metabolites in the myocardium and kidneys of rats with DM complicated by cerebral ischemia-reperfusion.  
Results. The content of protein oxidative modification products in the tissues of the kidneys and myocardium and the content of nitrogen monoxide metabolites in the cortical and medullary substance of the kidneys were found to decrease in the early ischemic-reperfusion period in rats without DM. In rats with DM early post-ischemic changes are restricted by the increase of nitrogen oxide metabolites content in the renal medullary substance. Total remote changes of the examined parameters are found in the myocardium of rats without DM and the medullary substance of the kidneys in rats with DM.   
Conclusions. Diabetes mellitus eliminates or restricts the reaction of the examined indices peculiar for control animals in both periods of observation in all the examined tissues except the medullary substance of the kidneys on the 12th day of the post-ischemic period

Tkachuk, O. V.

Akademicka Platforma Czasopism

English

https://apcz.umk.pl/JEHS/article/download/5804/pdf

Content of protein oxidative modification products and nitrogen monoxide metabolites in the kidneys and myocardium of rats with streptozotocin-induced diabetes in dynamics of cerebral ischemia-reperfusion

Abstract

Similar works

Full text

Available Versions

NEUROSURGERY ENTHUSIASTIC WOMEN SOCIETY

Directory of Open Access Journals

Akademicka Platforma Czasopism