title: Alagebrium attenuates methylglyoxal induced oxidative stress and AGE formation in H9C2 cardiac myocytes.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  ALA may have a preventive role against the deleterious effects of high glucose and MG in the heart. Prevention of dicarbonyl-induced AGEs, by safer and specific scavengers of MG is an attractive therapeutic option.
authors.affiliation: Department of Pharmacy, Birla Institute of Technology and Sciences Pilani, Hyderabad Campus, Jawahar Nagar, Shameerpet, Hyderabad, Andhra Pradesh 500078, India. Electronic address: artidhar@hyderabad.bits-pilani.ac.in.
authors.forename: Arti
authors.initials: A
authors.lastname: Dhar
authors.affiliation: Department of Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada.
authors.forename: Indu
authors.initials: I
authors.lastname: Dhar
authors.affiliation: Department of Microbiology & Immunology, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada.
authors.forename: Audesh
authors.initials: A
authors.lastname: Bhat
authors.affiliation: Department of Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada.
authors.forename: Kaushik M
authors.initials: KM
authors.lastname: Desai
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000096:biosynthesis; D002460:Cell Line; D002478:Cells, Cultured; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000096:biosynthesis; D018384:Oxidative Stress / Q000187:drug effects*; D011765:Pyruvaldehyde / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products / Q000096:biosynthesis; D013844:Thiazoles / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
chemical_list: C000593874:Ager protein, rat; C494828:Bax protein, rat; D016166:Free Radical Scavengers; D017127:Glycation End Products, Advanced; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D000067759:Receptor for Advanced Glycation End Products; D013844:Thiazoles; D051028:bcl-2-Associated X Protein; D011765:Pyruvaldehyde; C406794:alagebrium; C505410:Casp3 protein, rat; D053148:Caspase 3; D005947:Glucose
keywords: Alagebrium; Cardiomyocytes; Methylglyoxal; Oxidative stress; Receptor for advanced glycation endproducts