Inna SytnykBogomolets National Medical University, Ukraine
Title: Molecular mechanisms of cardioprotection of N-acetylcysteine and losartan in streptozotocin-induced type 1 diabetes mellitus
Diabetic complications especially diabetic cardiomyopathy decreases the life quality of patients with diabetes mellitus (DM) and often comes in a fatal outcome. Oxidative stress plays initial role in development of diabetic cardiomyopathy. Lately, the cardioprotective effect of antioxidant N-acetylcysteine in experimental studies has been actively discussed. Blocking the renin-angiotensin-aldosterone system seems to be essential in case of DM, perspective is treatment with angiotensin II type 1 receptor blockers. The study of level of lipoperoxidation as well as total antioxidant status is necessary for understanding of molecular mechanisms of cardioprotection.
The aim of the research was to detect molecular mechanisms of cardioprotection of N-acetylcysteine and losartan in case of streptozotocin-induced DM in rats.
Materials and methods:
Fatty acid composition of myocardium tissues was determined by a gas chromatography. Determination of thiobarbituric acid reactive substances, reduced glutathione, catalase activity and superoxide dismutase activity was determined spectrophotometrically. Expression of MMP-2 protein was determined according to the western blot analysis.
It was found that N-acetylcysteine (NAC ,1,5 g/kg) and losartan (LOS, 20 mg/kg) both have antioxidant activity due to increasing the level of unsaturated fatty acids (increase in the content of linoleic by 2,5 times and omega 3 linoleic acid in 2,3 times, p<0,05) and reduction of arachidonic acid content (by 1,4 times, p<0,05), which indicates a decrease in lipoperoxidation (2,2-fold decrease content of thiobarbiturate reactive substances, p<0,05) as well as an increase in the system of endogenous antioxidant defense of myocardium tissue (2,5 times increase in glutathione level; 1,6 and 1,7 times in the activity of superoxide dismutase, p<0,05). NAC more efficiently redistributed stearinic acid, increasing its content (by 1,3 times, p<0,05), indicating membrane -protective properties of myocardiocytes, and losartan – by the 2,7-fold increase of minor saturated fatty acids (myristic, pentadecanic, heptadecanic) (p<0,05). It was proved the antiproliferative action of NAC due to decreasing expression of MMP-2 protein by 20% (p<0.01).
The knowledge of molecular mechanisms of cardioprotective action of NAC and LOS was deepened. We have found that NAC and LOS provide antioxidant activity due to increasing the level of linoleic acid and linolenoic acid content, reduction of arachidonic acid content as well as an increase in the system of endogenous antioxidant defense of myocardium tissue. New data of the membrane-stabilizing effect of NAC and LOS were also indicated. It was proved antiproliferative action of NAC resulted by decreasing the expression of MMP-2 protein.
Inna Sytnyk, pharmacist, obtained PhD in Pharmacology (Pharmaceutical sciences) in 2019. Since 2017 she has been working as assistant professor at Bogomolets National Medical University at department of Clinical Pharmacology and Clinical Pharmacy. There were more than 20 articles published by Inna Sytnyk. Currently she is consulting pharmacist at Department of Hepatology at State Institution "Institute of Pediatrics, Obstetrics and Gynecology of NAMS of Ukraine"