The Impact of Metformin and Rosuvastatin on the Markers of Oxidative Stress, Glycemic Control, and Lipid Profile in Rats With Streptozotocin-Nicotinamide-Induced Diabetes After Acute Intracerebral Hemorrhage

Abstract

Hyperproduction of highly active carbonyl compounds and reactive oxygen species initiates the development of oxidative stress in various pathological conditions and protein carbonylation is considered to be one of the key factors in the progression of diabetes mellitus and associated complications. This comparative research aimed to study the effect of metformin and rosuvastatin on the levels of biochemical markers of oxidative stress, glycemic control, and lipid profile in rats with type 2 diabetes mellitus (T2DM) complicated by a brain hemorrhage.T2DM was simulated with a single intraperitoneal injection of nicotinamide and streptozotocin (NA/STZ) to male Wistar rats (n=38). Intracerebral hemorrhage (ICH) was induced by microinjection of 1 μL of bacterial collagenase 0.2 IU/μL into the striatum. Animals were randomized into 5 groups: negative control, intact rats; positive control 1, NA/STZ; positive control 2, NA/STZ+ICH; metformin, 250 mg/kg +NA/STZ+ICH; rosuvastatin, 15 mg/kg+NA/STZ+ICH. Drug effects were assessed by the area under the glycemic curve (AUC), the content of glucose, glycated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), homocysteine (Hcy), advanced glycation end products (AGEs), and the markers of oxidative modification of proteins – aldehyde- and ketonephenylhydrazones (APH/KPH) in blood serum.It was found that brain hemorrhage in rats with T2DM can intensify the manifestations of oxidative modification of molecules and worsen glycemic control and lipid profile. Under these conditions, rosuvastatin improved lipid metabolism and reduced the levels of AGEs by 35.1% but did not affect glycemia and content of APH/KPH. Metformin reduced oxidative stress (AGEs by 35.4%, KPH by 21.2%) as well as improved both glycemic status and lipid profile (TG level by 20.2%, TG/HDL ratio by 31.9%). Both drugs did not produce any effect on Hcy level.Thus, metformin in conditions of T2DM complicated by acute ICH has advantages over rosuvastatin in relation to the markers of oxidative modification and glycemic control.