Starch-deferoxamine conjugate inhibits hepatocyte Ca2+ uptake during hemorrhagic shock and resuscitation.
BACKGROUND
This study investigated whether hepatocyte Ca2+ dysregulation after hemorrhagic shock and resuscitation could be modulated by the iron chelator hydroxyethyl starch-conjugated deferoxamine (HES-DFO).


METHODS
In a randomized experimental study, anesthetized rats (n = 7) were bled for 60 minutes to maintain mean arterial blood pressure at 40 mm Hg. They were then resuscitated with 60% of shed blood and threefold the shed-blood volume as lactated Ringer's solution, 1 mL of pentastarch solution (hydroxyethyl starch 10%) per mL of shed blood, or 1 mL of HES-DFO solution (10%) per mL of shed blood. In isolated hepatocytes, the rate of Ca2+ influx (Ca2+ in), total Ca2+ uptake (Ca2+ up), and membrane Ca2+ flux (Ca2+ flux) were determined by 45Ca incubation. Reduced or oxidized glutathione and malondialdehyde concentrations were assessed fluorometrically.


RESULTS
Significant increases of hepatocellular Ca2+ in, Ca2+ up, and Ca2+ flux were observed in rats resuscitated with lactated Ringer's solution compared with control groups (p < 0.05). Although hydroxyethyl starch decreased Ca2+ in but not Ca2+ up, HES-DFO not only prevented the increase of Ca2+ in and Ca2+ up but also inhibited hepatocyte oxidative injury.


CONCLUSIONS
Iron-catalyzed oxyradical production and membrane peroxidation seem to alter hepatocyte Ca2+ homeostasis after hemorrhagic shock and resuscitation.
Rose
S
S
Department of Trauma, Hand and Reconstructive Surgery, University of Saarland, Homberg, Germany. chsros@med-rz.uni-sb.de
Pizanis
A
A
Silomon
M
M
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003676:Deferoxamine / Q000494:pharmacology*; D004195:Disease Models, Animal; D006439:Hemodynamics / Q000187:drug effects; D006895:Hydroxyethyl Starch Derivatives / Q000494:pharmacology*; D007502:Iron Chelating Agents / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015532:Rehydration Solutions / Q000494:pharmacology*; D015427:Reperfusion Injury / Q000517:prevention & control; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000097:blood / Q000628:therapy*
D006895:Hydroxyethyl Starch Derivatives; D007502:Iron Chelating Agents; D015532:Rehydration Solutions; C068460:hydroxyethyl starch-deferoxamine conjugate; D003676:Deferoxamine; D002118:Calcium