title: Involvement of calcium, reactive oxygen species, and ATP in hexavalent chromium-induced damage in red blood cells.
abstract: OBJECTIVE
  The aim of this study was to investigate the mechanisms of Cr(6+)-induced red blood cells (RBCs) damage.
  
  
  METHODS
  The effect of Cr(6+) exposure on RBCs was evaluated by hemolytic rate and blood gas assays. After exposure to 20 μM Cr(6+), the percentage of phosphatidylserine (PS)-exposing cells, intracellular Ca(2+), reactive oxygen species (ROS), and ATP levels were evaluated, and cell morphology was observed. RBCs were exposed to Cr(6+) in different Ringer solutions to investigate the role of changes of Ca(2+), ROS, and ATP levels in eryptosis and morphology.
  
  
  RESULTS
  The Cr(6+)-induced damage of RBCs was dose-dependent. After a 6 h incubation with Cr(6+), RBCs exhibited significant Ca(2+) influx, ROS increase, ATP depletion, and PS exposure, but displayed no obvious change in morphology at this time point. After 24 h Cr(6+) exposure, the RBCs decreased in size, appeared to be spike-like, and had decreased forward scatter. Inhibition of Ca(2+) influx attenuated PS-exposure caused by 6 h Cr(6+) exposure, but did not prevent 24 h Cr(6+) exposure-induced morphological change in RBCs. Inhibition of rapid ATP consumption using adenine significantly ameliorated Cr(6+)-caused PS-exposure at 12 h, 24 h and 48 h, and prevented 24 h Cr(6+) incubation-induced morphological change in RBCs.
  
  
  CONCLUSIONS
  Cr(6+) can lead to eryptosis. Ca(2+) influx, increased ROS levels, and rapid ATP consumption are closely related to Cr(6+)-induced RBCs damage. Ca(2+) influx plays an extremely important role in Cr(6+)-mediated toxicity.
authors.affiliation: Department of Blood Transfusion, The Second Affiliated Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.forename: Yang
authors.initials: Y
authors.lastname: Xiang
authors.forename: Qian
authors.initials: Q
authors.lastname: Ran
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Deng
authors.forename: Yanni
authors.initials: Y
authors.lastname: Xiao
authors.forename: Lixin
authors.initials: L
authors.lastname: Xiang
authors.forename: Zhongjun
authors.initials: Z
authors.lastname: Li
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002857:Chromium / Q000009:adverse effects*; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D017382:Reactive Oxygen Species; D002857:Chromium; C074702:chromium hexavalent ion; D000255:Adenosine Triphosphate; D002118:Calcium