<abstract xmlns="http://www.w3.org/1999/xhtml">

<p>Diabetic cardiomyopathy increases the risk of heart failure and worsens prognosis for diabetes mellitus (DM) patients. Its development depends on many factors, including modification of nitric oxide production and impaired DNA repair. The goal of the present work was to study <italic>in vivo</italic> effects of a 1,4-dihydropyridine AV-153, known as antimutagen and DNA-binder, on DNA integrity, and on the expression of several proteins involved in glucose transport, nitric oxide metabolism, and DNA repair in myocardium in diabetic rats. DM was induced in rats by streptozotocin (STZ) injection. Expression of proteins was studied by means of immunohistochemistry. Development of the STZ-induced DM significantly induced PARP1 and gamma H2AX histone, markers of DNA breakage, protein expression in heart tissue, while AV-153 administration decreased PARP1 and H2AX protein expression. In this model of diabetes, myocardial expression of iNOS was also significantly increased, but administration of AV-153 reduced it to normal levels. AV-153 also upregulated the expression of insulin-dependent GLUT4 and insulin-independent GLUT1 glucose transporters up to normal level in diabetic rats. Thus, AV-153 appears to be prospective for creation of a remedy for prevention of diabetic cardiomyopathy.</p>
</abstract>

Diabetic cardiomyopathy increases the risk of heart failure and worsens prognosis for diabetes mellitus (DM) patients. Its development depends on many factors, including modification of nitric oxide production and impaired DNA repair. The goal of the present work was to study in vivo effects of a 1,4-dihydropyridine AV-153, known as antimutagen and DNA-binder, on DNA integrity, and on the expression of several proteins involved in glucose transport, nitric oxide metabolism, and DNA repair in myocardium in diabetic rats. DM was induced in rats by streptozotocin (STZ) injection. Expression of proteins was studied by means of immunohistochemistry. Development of the STZ-induced DM significantly induced PARP1 and gamma H2AX histone, markers of DNA breakage, protein expression in heart tissue, while AV-153 administration decreased PARP1 and H2AX protein expression. In this model of diabetes, myocardial expression of iNOS was also significantly increased, but administration of AV-153 reduced it to normal levels. AV-153 also upregulated the expression of insulin-dependent GLUT4 and insulin-independent GLUT1 glucose transporters up to normal level in diabetic rats. Thus, AV-153 appears to be prospective for creation of a remedy for prevention of diabetic cardiomyopathy.

Antimutagenic 1,4-Dihydropyridine AV-153 Normalizes Expression of GLUT1, GLUT4, INOS, PARP1, and Gamma H2AX Histone in Myocardium of Rats with Streptozotocin Model of Diabetes Mellitus

Proceedings of the Latvian Academy of Sciences. Section B. Natural, Exact, and Applied Sciences.

This work is licensed under the Creative Commons Attribution 4.0 International License.

Diabetic cardiomyopathy increases the risk of heart failure and worsens prognosis for diabetes mellitus (DM) patients. Its development depends on many factors,...

Antimutagenic 1,4-Dihydropyridine AV-153 Normalizes Expression of GLUT1, GLUT4, INOS, PARP1, and Gamma H2AX Histone in Myocardium of Rats with Streptozotocin Model of Diabetes Mellitus

Data publikacji: 18 maj 2023

Zakres stron: 96 - 101

Otrzymano: 08 lut 2021

Przyjęty: 28 mar 2023

DOI: https://doi.org/10.2478/prolas-2023-0014

Słowa kluczowe
diabetic cardiomyopathy, nitric oxide, DNA damage, glucose transporters

© 2023 Evita Rostoka et al., published by Sciendo

This work is licensed under the Creative Commons Attribution 4.0 International License.

Antimutagenic 1,4-Dihydropyridine AV-153 Normalizes Expression of GLUT1, GLUT4, INOS, PARP1, and Gamma H2AX Histone in Myocardium of Rats with Streptozotocin Model of Diabetes Mellitus

Data publikacji: 18 maj 2023

Zakres stron: 96 - 101

Otrzymano: 08 lut 2021

Przyjęty: 28 mar 2023

DOI: https://doi.org/10.2478/prolas-2023-0014

Słowa kluczowediabetic cardiomyopathy, nitric oxide, DNA damage, glucose transporters

© 2023 Evita Rostoka et al., published by Sciendo

This work is licensed under the Creative Commons Attribution 4.0 International License.

Słowa kluczowe
diabetic cardiomyopathy, nitric oxide, DNA damage, glucose transporters