Propaedeutic of Internal Diseases Department, Medical Faculty, Trakia University Hospital, 6000 Stara Zagora, Bulgaria.
Medical Chemistry and Biochemistry Department, Medical Faculty, Trakia University, 11 Armeiska Str., 6000 Stara Zagora, Bulgaria.
Int J Mol Sci. 2023 Aug 31;24(17):13541. doi: 10.3390/ijms241713541.
The present study aimed to investigate and compare biomarkers of oxidative stress and the activity of antioxidant enzymes in the plasma of patients with different stages of diabetic nephropathy. For this purpose, we studied (1) the levels of reactive oxygen species and reactive nitrogen species as oxidative stress parameters, (2) lipid and protein oxidation, (3) the activity of antioxidant enzymes, and (4) cytokine production. Patients with type 2 diabetes mellitus were divided into three groups according to the loss of renal function: patients with compensated diabetes mellitus with normal renal function DMT2N0 measured as an estimated glomerular filtration rate (eGFR) ≥ 90 mL/min/1.73 m, a group with decompensated diabetes mellitus with complication diabetic nephropathy and mild-to-moderate loss of renal function DMT2N1 (eGFR < 60 mL/min/1.73 m: 59-45 mL/min/1.73 m), and a decompensated diabetes mellitus with diabetic nephropathy group with moderate-to-severe loss of renal function DMT2N2 (eGFR > 30 mL/min/1.73 m: 30-44 mL/min/1.73 m). All results were compared with healthy volunteers. The results showed that patients with diabetic nephropathy had significantly higher levels of ROS, cytokine production, and end products of lipid and protein oxidation compared to healthy volunteers. Furthermore, patients with diabetic nephropathy had depleted levels of nitric oxide (NO), an impaired NO synthase (NOS) system, and reduced antioxidant enzyme activity ( < 0.05). These findings suggest that patients with impaired renal function are unable to compensate for oxidative stress. The decreased levels of NO radicals in patients with advanced renal complications may be attributed to damage NO availability in plasma. The study highlights the compromised oxidative status as a contributing factor to impaired renal function in patients with decompensated type 2 diabetes mellitus. The findings of this study have implications for understanding the pathogenesis of diabetic nephropathy and the role of oxidative stress and chronic inflammation in its development. The assessment of oxidative stress levels and inflammatory biomarkers may aid in the early detection and prediction of diabetic complications.
本研究旨在探讨和比较不同阶段糖尿病肾病患者血浆中氧化应激生物标志物和抗氧化酶活性。为此,我们研究了:(1)活性氧和活性氮作为氧化应激参数的水平;(2)脂质和蛋白质氧化;(3)抗氧化酶的活性;(4)细胞因子的产生。2 型糖尿病患者根据肾功能丧失情况分为三组:肾功能正常的代偿性糖尿病患者(DMT2N0),用估算肾小球滤过率(eGFR)≥90mL/min/1.73m 来衡量;伴有轻度至中度肾功能丧失的并发症糖尿病肾病患者(DMT2N1,eGFR<60mL/min/1.73m:59-45mL/min/1.73m);伴有中度至重度肾功能丧失的糖尿病肾病患者(DMT2N2,eGFR>30mL/min/1.73m:30-44mL/min/1.73m)。所有结果均与健康志愿者进行比较。结果表明,与健康志愿者相比,糖尿病肾病患者的 ROS、细胞因子产生以及脂质和蛋白质氧化的终产物水平显著升高。此外,糖尿病肾病患者的一氧化氮(NO)水平降低,NO 合酶(NOS)系统受损,抗氧化酶活性降低(<0.05)。这些发现表明,肾功能受损的患者无法代偿氧化应激。在伴有晚期肾并发症的患者中,NO 自由基水平降低可能归因于血浆中 NO 可用性的损害。该研究强调了氧化状态受损是代偿性 2 型糖尿病患者肾功能受损的一个促成因素。本研究的结果对于理解糖尿病肾病的发病机制以及氧化应激和慢性炎症在其发展中的作用具有重要意义。氧化应激水平和炎症生物标志物的评估可能有助于早期发现和预测糖尿病并发症。