The Effect of Actovegyn on the Mechanisms of Oxidative Stress Developing in Patients With Type 2 Diabetes Mellitus and Cardiovascular Autonomic Neuropathy

Abstract

The effects of actovegin on the mechanisms of oxidative stress (OS) developing in the blood of patients with type 2 diabetes mellitus (DM2) and cardiovascular autonomic neuropathy (CVAN) were investigated. The aim of the study was to establish the effectiveness of treatment with actovegin for the pro- and antioxidant balance impairment and changes in gene expression of HIF-1α and mTOR in the blood of patients with DM2 and CVAN. It was shown that intravenous injections of actovegin at a dose of 1000 mg per day for 10 days and further prolonged oral administration of this drug at a dose of 800 mg per day for 90 days led to a decrease in the content of secondary products of lipid peroxidation in blood plasma and H2O2 production in erythrocytes of patients with DM2 and CVAN. These changes were indicative of a weakening of OS intensity. It was also shown that treatment with actovegin promoted an increase in total plasma SOD activity as well as reduced glutathione and glutathione peroxidase activity in erythrocytes from patients. Treatment with actovegin also raised the gene expression of HIF-1α and reduced the gene expression of mTOR in leukocytes of patients with DM2 and CVAN. These genetic changes may serve as a protective mechanism against the development of OS, which acts through different metabolic pathways. So, actovegin administration counteracting OS development due to the impact on the different components of pro- and antioxidant system as well as on HIF-1α and mTOR genes expression may offer new clinical avenues for pharmacological treatment of patients with DM2 and CVAN.