Trimetazidine Prevents Diabetic Cardiomyopathy by Inhibiting Nox2/TRPC3-induced Oxidative Stress

Publication date: Available online 15 March 2019Source: Journal of Pharmacological SciencesAuthor(s): Sheng-gao Tang, Xiao-yu Liu, Shan-ping Wang, Hong-hui Wang, Aleksandar Jovanović, Wen TanAbstractDiabetic cardiomyopathy (DCM) is characterized by cardiac hypertrophy, fibrosis, oxidative stress and inflammation. Trimetazidine (TMZ), a potent metabolism modulator, has been shown to be cardioprotective in experimental models of ischaemia-reperfusion and type 2 diabetes-induced cardiomyopathy. The present study examined whether TMZ inhibits cardiomyopathy induced by insulin-dependent type 1 diabetes. Wistar rats were randomly divided into control group (vehicle alone), Diabetes mellitus (DM; induced by streptozocin (STZ) injection) group and DM treated with TMZ (DM/TMZ) group. Cardiac function, histology, plasma biochemistry and molecular mechanism were assessed. STZ induced diabetes in rats as indicated by hyperglycemia, increased and decreased levels of advanced glycation end products (AGEs) and insulin respectively. Diabetic rats were characterized by left ventricular dysfunction, cardiachypertrophy and fibrosis and signs of inflammation and oxidative stress in the myocardium, which were accompanied by elevated levels of NADPH oxidase 2 (Nox2) and transient receptor potential channel 3 (TRPC3) in the heart.TMZ treatment ameliorated diabetes-associated structural and functional alterations by inhibiting Nox2 and TRPC3without having any effects on glucose, insulin and AGEs le...
Source: Journal of Pharmacological Sciences - Category: Drugs & Pharmacology Source Type: research