INTENSITY OF OXIDATIVE STRESS AS A UNIVERSAL MECHANISM OF TISSUE DAMAGE IN NONALCOHOLIC STEATOHEPATITIS AND DIABETIC KIDNEY DISEASE IN PATIENTS WITH TYPE 2 DIABETES MELLITUS. QUERCETIN CORRECTION EFFECTIVENESS

Abstract

The objective of the research was to determine the intensity of the effect of a complex of Metformin, Rosuvastatin, Essentiale Forte N and Quercetin on the state of oxidative-antioxidant homeostasis, as well as the intensity of hepatocyte apoptosis by cytokeratin-18 in the blood that are the factors in the progression of nonalcoholic steatohepatitis and diabetic kidney disease.

Material and methods. 75 patients with non-alcoholic steatohepatitis with type 2 diabetes mellitus and stage I­–III diabetic kidney disease were studied over time. According to the prescribed treatment, the examined patients were divided into 2 groups: (group 1 ­– the controls: 37 patients) received a low-calorie diet with dietary restrictions No.9, essential phospholipids (Essentiale forte H 300 mg 2 caps. 3 times a day) for 30 days for the treatment of active non-alcoholic steatohepatitis, Metformin Hydrochloride (Metformin-Teva) 1000 mg per day, Rosuvastatin (Rosuvastatin-Teva 5 mg once daily) for 1 month for concomitant type 2 diabetes mellitus and hyperlipidemia. Group 2 consisted of patients (38 people) who in addition to similar dietary recommendations and therapy received additionally Quercetin and Povidone (Corvitin) 500 mg intravenously per 100 ml of isotonic chloride for 10 days.

Results. It was found that the comorbid course of nonalcoholic steatohepatitis and diabetic kidney disease in patients with type 2 diabetes mellitus is accompanied by a significant increase in the intensity of oxidative stress, accompanied by an increase in blood intermediate and final products of lipid peroxidation. The damaging effect of oxidative stress in patients with type 2 diabetes mellitus leads to the activation of apoptosis of hepatocytes with an increase in blood cytokeratin-18 (7.5 times, p < 0.05), the content of which correlates with the degree of oxidative stress, the intensity of liver damage and stage of diabetic kidney disease (p < 0.05). Oxidative stress increases the risk of endothelial damage by atherosclerotic process due to hyperproduction of homocysteine (3.9 times, p < 0.05), which contributes to the progression of diabetic kidney disease. The use of Quercetin in the complex therapy of non-alcoholic steatohepatitis and type 2 diabetes mellitus with diabetic kidney disease contributes to the reduction of oxidative stress, increased activity of antioxidant defense factors (content of reduced glutathione in erythrocytes, reduction of cytokeratin-18 content by 1.7 times) and endothelial damage (reduction of homocysteine content in blood by 1.9 times) (p < 0.05).

Conclusions. The comorbid course of nonalcoholic steatohepatitis and diabetic kidney disease in patients with type 2 diabetes mellitus is accompanied by a significant increase in the intensity of oxidative stress, and in the content of intermediate and final products of lipid peroxidation and oxidative modification of proteins (p < 0.05).