Low osmolar contrast medium induces cellular injury and disruption of calcium homeostasis in rat glomerular endothelial cells in vitro

Toxicol Lett. 2009 Mar 10;185(2):124-31. doi: 10.1016/j.toxlet.2008.12.009. Epub 2008 Dec 24.

Abstract

The mechanisms of contrast medium (CM)-induced renal impairment at cellular level are not fully understood. The purpose of this study was to investigate the toxic effects of non-ionic low osmolar contrast medium (LOCM) on glomerular endothelial cells (GECs). Ioversol, the most representative LOCM used in clinic, was chosen to act on primary cultured rat GECs. When rat GECs were treated with various amount of ioversol, a dose-dependent reduction in cell viability was observed by tetrazolium dye (MTT) assay. After exposure to ioversol at dose of 100 microl/ml for 24h, nuclear condensation, nuclear fragmentation, cell apoptosis and necrosis were found in GECs. The intracellular free Ca(2+) concentrations ([Ca(2+)]i) detected by confocal laser scanning were markedly elevated in GECs treated with ioversol. The [Ca(2+)]i increase, LDH release and expression changes of apoptotic associated proteins in GECs induced by ioversol could be reversed by pretreatment with intracellular Ca(2+) chelator, 1,2-bis (o-aminophenoxy) ethane-N,N,N',N'-tetra-acetic acid (BAPTA/AM). These results suggest that LOCM can decrease cell viability and cause cell injury of GECs. The elevation of [Ca(2+)]i released from intracellular calcium stores likely contribute to the LOCM-induced cell injury of GECs.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Benzimidazoles / toxicity
  • Blotting, Western
  • Calcium / metabolism*
  • Cell Nucleus / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Contrast Media / toxicity*
  • Dose-Response Relationship, Drug
  • Endothelial Cells / drug effects*
  • Endothelial Cells / pathology
  • Homeostasis / drug effects*
  • Kidney Glomerulus / drug effects*
  • Kidney Glomerulus / pathology
  • L-Lactate Dehydrogenase / metabolism
  • Male
  • Osmolar Concentration
  • Propidium / toxicity
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Benzimidazoles
  • Contrast Media
  • Propidium
  • L-Lactate Dehydrogenase
  • bisbenzimide ethoxide trihydrochloride
  • Calcium