The protective effect of metformin on hypertriglyceridemia-induced dicarbonyl stress in serum and tissues

Abstract

s / Atherosclerosis 241 (2015) e32ee71 e58 EAS-0142. THE PROTECTIVE EFFECT OF METFORMIN ON HYPERTRIGLYCERIDEMIAINDUCED DICARBONYL STRESS IN SERUM AND TISSUES V. Skop, H. Malinska, J. Trnovska, L. Kazdova. Center for Experimental Medicine, Institute for Clinical and Experimental Medicine Prague Czech Republic, Prague 4, Czech Republic Biogenesis of reactive dicarbonyls leads to the production of advanced glycation end products, increases oxidative stress, and play a key role in the development of diabetic vascular complications. Metformin is the most widely prescribed glucose-lowering agent; however, its effect on dicarbonyls metabolism in tissues is not clarified. In our study we analyzed levels of individual reactive dicarbonyls e methylglyoxal (MG), glyoxal (GL) and 3-deoxyglucosone (3-DG) in relation to lipid disorders and after metformin administration (300 mg/kg b.wt.) in non-obese hereditary hypertriglyceridemic (HHTg) rats. The concentration of dicarbonyls were determined by derivatisation with 1,2-diamino-4,5-dimethoxy-benzene and HPLC-method with fluorescence detection. Compared with control Wistar rats, HHTg rats exhibited markedly increased serum level of GL (+89%) and MG (+179%), increased levels of GL (+189%), MG (+73%) and 3-DG (+114%) in myocardium and increased level of GL (+59%) and MG (+57%) in kidney cortex. Metformin treatment significantly reduced level of reactive dicarbonyls in the myocardium (Gl: -31%; MG: -15%; 3-DG: -49%) and reduced level of MG (-49%) in serum. However, dicarbonyls concentrations in the kidney cortex were not affected by metformin. Changes in dicarbonyls concentrations were accompanied by changes in glutathione metabolism. Metformin prevents negative effect of hypertriglyceridemia on GSH/GSSG ratio and total glutathione content in myocardium, but neither hypertriglyceridemia nor metformin affects glutathione metabolism in kidney cortex. Results indicate that hypertriglyceridemia is associated with increased dicarbonyl stress in serum and tissues. Beneficial effect of metformin therapy on reactive dicarbonyls in heart could contribute to its cardioprotective effects. Supported by the grant GACR P303/13-04420S EAS-0202. MILK INTAKE IS NOT CAUSALLY ASSOCIATED WITH RISK OF ISCHEMIC HEART DISEASE OR MYOCARDIAL INFARCTION e A MENDELIAN RANDOMIZATION STUDY IN 98,529 DANISH INDIVIDUALS H.K.M. Bergholdt , B.G. Nordestgaard , A. Varbo , C. Ellervik . Dept. of Clinical Biochemistry, Naestved Hospital, Naestved, Denmark; Dept. of Clinical Biochemistry, Copenhagen University Hospital, Herlev, Denmark; 3 Faculty of Health and Medical Sciences, University of Copenhagen,