Clinical evidence suggests that type 2 diabetes mellitus can increase the risk of intracerebral hemorrhage and provocation of neurodegeneration. This study was aimed at evaluating biomarkers of glycemic control, lipid profile, oxidative modification of proteins, as well as the functional state of endothelium in Wistar rats with type 2 diabetes mellitus complicated by intracerebral hemorrhage. Experimental type 2 diabetes mellitus was induced by intraperitoneal injection of streptozotocin (65 mg/kg) and nicotinamide (230 mg/kg). The intracerebral hemorrhage was induced by microinjection of sterile saline containing 0.2 IU bacterial collagenase into the striatum. Assessed biomarkers included the area under glycemic curve, glycated hemoglobin, total cholesterol, triglyceride, high-density lipoprotein, advanced glycation end products, markers of oxidative modification of proteins – aldehyde- and ketonephenylhydrazones, and markers of endothelial dysfunction – homocysteine, endothelin-1, von Willebrand factor and asymmetric dimethylarginine in blood serum. Both rats with type 2 diabetes mellitus and rats with intracerebral hemorrhage and diabetes had a significant elevated glycemic control as compared to intact animals. But combined pathology was additionally characterized by an impairment of lipid profile (increased triglyceride level and decreased as total cholesterol and high-density lipoprotein) resulting in a rise in the atherogenic index of plasma. A significant increase in the content of the markers of oxidative modification of proteins was observed in both experimental groups. But the rats with intracerebral hemorrhage and diabetes only had higher levels of advanced glycation end products in comparison with intact animals. The highest levels of endothelin-1, as a biomarker of endothelial dysfunction, were observed in animals with intracerebral hemorrhage and diabetes. Homocysteine and von Willebrand factor were elevated in rats with type 2 diabetes mellitus, while acute intracerebral hemorrhage did not potentiate the further growth in its levels. Such effect was not accompanied by a marked increase of asymmetric dimethylarginine level in blood serum, although there was a clear trend. In conclusion, the development of intracerebral hemorrhage in rats with type 2 diabetes mellitus can intensify the manifestations of oxidative stress, worsen lipid profile, and aggravate endothelial dysfunction. In this case, the pathological process may have the character of a “vicious circle”.
В обзорной статье представлены сведения, касающиеся фармакодинамики, фармакокинетики, клинической эффективности и безопасности длительной терапии ацетилсалициловой кислотой (АСК) пациентов с сердечно-сосудистыми заболеваниями. Показаны основные практические способы уменьшения возможных осложнений со стороны желудочно-кишечного тракта. Убедительные положительные результаты клинических испытаний и так называемая желудочная токсичность АСК наряду с необходимостью длительного применения препарата в качестве антиагреганта стали основанием для появления различных лекарственных форм АСК: растворимых, с контролируемым высвобождением, покрытых кишечнорастворимой оболочкой, локальных, буферных, а также комбинированных средств, сочетающих в себе АСК и вещества с антацидным эффектом. К настоящему времени наиболее убедительные доказательства эффективности и гастроинтестинальной безопасности получены для кишечнорастворимых форм АСК.
Introduction:
Diabetes mellitus is associated with the development of carbonyl-oxidative stress (COS) and an increased risk of a cerebral hemorrhage. Vitamin D3 is considered an additional drug to have an impact on COS and proteolysis in the extracellular matrix.
background:
Diabetes mellitus is associated with the development of carbonyl-oxidative stress (COS) and an increased risk of a cerebral hemorrhage. Vitamin D3 is considered as an additional drug to have an impact on COS and proteolysis in the extracellular matrix.
Objective:
The study aimed to evaluate the impact of D3 on the COS-markers and matrix metalloproteinases MMP2/MMP9 activity after acute intracerebral hemorrhage (ICH) in rats with experimental type 2 diabetes mellitus (Т2DM) compared to metformin (Met).
objective:
To evaluate the impact of D3 on the COS-markers and matrix metalloproteinases MMP2/MMP9 activity after acute intracerebral hemorrhage (ICH) in rats with experimental type 2 diabetes mellitus (Т2DM) compared to metformin (Met).
Methods:
T2DM was induced in rats via the intraperitoneal injection of streptozotocin (STZ) and nicotinamide (NA), ICH – by microinjection of bacterial collagenase into the striatum. Rats were randomized into five groups: 1 – intact animals (n=8), 2 – T2DM (n=9); 3 – T2DM+ICH (n=7); 4 – T2DM+ICH+Met (n=7); 5 – T2DM+ICH+D3 (n=7). Blood glucose, glycated hemoglobin, and oral glucose tolerance test (OGTT) were assessed using commercial kits. Advanced oxidation protein products (AOPP), protein carbonyls (PC370/430), and ischemia-modified albumin (IMA) were measured by spectrophotometry, advanced glycation end products (AGEs) by quantitative fluorescence, and matrix metalloproteinases MMP2/9 by gelatin zymography.
method:
T2DM was induced in rats via the intraperitoneal injection of streptozotocin (STZ) and nicotinamide (NA), ICH – by microinjection of bacterial collagenase into the striatum. Rats were randomized into five groups: 1 – intact animals (n=8), 2 – T2DM (n=9); 3 – T2DM+ICH (n=7); 4 – T2DM+ICH+Met (n=7); 5 – T2DM+ICH+D3 (n=7). Blood glucose, glycated hemoglobin and oral glucose tolerance test (OGTT) were assessed using commercial kits. Advanced oxidation protein products (AOPP), protein carbonyls (PC370/430), and ischemia modified albumin (IMA) were measured by spectrophotometry, advanced glycation end products (AGEs) – by quantitative fluorescence, matrix metalloproteinases MMP2/9 – by gelatin zymography.
Results:
D3 does not significantly affect the glucose level and OGTT in rats with T2DM+ICH. However, it reduces AOPP, PC, and AGEs, thus reducing the COS index. In contrast, the activity of proMMP9 increases after D3 administration. These effects of D3 have been reported to be stronger and sometimes opposite to those of metformin.
Conclusion:
D3 supplementation may decrease the negative consequences of a cerebral hemorrhage in T2DM by reducing COS and preventing the accumulation of COS-modified proteins in the brain by regulating the expression and activity of MMP9.
other:
All authors declared that there is no financial/commercial conflict of interest related to this paper.
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