Alagebrium attenuates methylglyoxal induced oxidative stress and AGE formation in H9C2 cardiac myocytes

Life Sciences
Arti DharKaushik Desai

Abstract

Diabetes mellitus associated cardiovascular complications are a leading cause of morbidity and mortality worldwide. Methylglyoxal (MG) is a reactive ketoaldehyde and a byproduct of glucose metabolism and an inducer of advanced glycation endproducts (AGEs). Alagebrium (ALA) is an AGEs crosslink breaker, however, the effects of ALA on MG levels and its consequences in cultured rat cardiomyocytes are not known. The aim of the present study was to examine the effect of high glucose and MG on cultured rat cardiomyocytes and to investigate whether ALA could prevent any deleterious effects of high glucose and MG in these cells. MG levels were determined by HPLC. The expression of different genes was measured by RT-PCR. Oxidative stress and AGEs formation was determined by DCF probe and immunocytochemistry respectively. High glucose- and MG treated- cardiomyocytes developed a significant increase in MG, and the expression for caspase-3, Bax, RAGE and NF-KB, which were all attenuated after pretreatment with ALA. A significant increase in reactive oxygen species generation and AGEs formation in high glucose- and MG treated- cultured cardiomyocytes was also observed, which was attenuated after pretreatment with ALA. ALA may have a prevent...Continue Reading

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