Pathogenetic rationale for correction of endothelial dysfunction with quercetin in the complex treatment of non-alcoholic steatohepatitis and diabetic kidney disease in patients with type 2 diabetes mellitus

Abstract

Objective — to determine effects of therapeutical complex, including metformin, rosuvastatin, essential phospholipids and quercetin, on the state of blood lipid spectrum, endothelial function, fibrinolysis system and platelet hemostasis, which are factors in the progression of nonalcoholic steatohepatitis (NASH) and diabetic kidney disease (DKD).
 Materials and methods. The investigation was performed in the dynamics of treatment of 60 NASH patients with type 2 diabetes mellitus (DM 2) and DKD of stage I — III. Depending on the prescribed treatment patients were randomized into 2 groups. The comparison group 1 (28 subjects) was administered hypocaloric diet with account of dietary restrictions #9, received essential phospholipids 300 mg 2 caps. 3 times a day) during 30 days for the NASH treatment, and antidiabetic and lipid‑lowering therapy with metformin hydrochloride 1000 mg per day, rosuvastatin (5 mg 1 time per day) for 1 month. Group 2 consisted of 32 patients and in addition to the similar 30 days of dietary recommendations, essential phospholipids, hypoglycemic and hypolipidemic therapy, received quercetin and povidone 500 mg intravenously in 100 ml of isotonic sodium 10 mg for 10 days. The mean age of patients was 53.8 ± 3.52 years. The comparison group consisted of 30 healthy age‑matching subjects.
 Results. Parameters of endothelial dysfunction, fibrinolysis and platelet hemostasis were determined to check the degree of endothelial‑protective effects of Quercetin against the background of the recommended protocol therapy. As a result of treatment, baseline significantly reduced NO levels (in 1.7 times) in patients of group 1 increased insignificantly (p > 0.05), and significantly raised in 1.5 times (p < 0.05) in group 2. This can be explained by effects of Quercetin as an endothelial protector, as well as by metformin effects, which reduces degree of insulin resistance and promotes body weight reduction, as well as reduction of hyperlipidemia level and probability of deposition of subendothelial proatherogenic fractions.
 Conclusions. Combined therapy of NASH with DM 2 and diabetic kidney disease with the use of essential phospholipids, statins and metformin with addition of Quercetin was more effective than traditional therapy: it significantly reduced the markers of NASH exacerbation, optimized blood lipid spectrum, restored endothelial functional state, eliminated the phenomena of hypercoagulable syndrome without the additional administration of antiplatelet agents.