Starch-deferoxamine conjugate inhibits hepatocyte Ca2+ uptake during hemorrhagic shock and resuscitation.

Background: This study investigated whether hepatocyte Ca 2+ 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, I 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 Ca 2+ influx (Ca 2+ in), total Ca 2+ uptake (Ca 2+ up), and membrane Ca 2+ flux (Ca 2+ flux) were determined by 45 Ca incubation. Reduced or oxidized glutathione and malondialdehyde concentrations were assessed fluorometrically. Results: Significant increases of hepatocellular Ca 2+ in, Ca 2+ up, and Ca 2+ flux were observed in rats resuscitated with lactated Ringer's solution compared with control groups (p < 0.05). Although hydroxyethyl starch decreased Ca 2+ in but not Ca 2+ up, HES-DFO not only prevented the increase of Ca 2+ in and Ca 2+ up but also inhibited hepatocyte oxidative injury. Conclusion: Iron-catalyzed oxyradical production and membrane peroxidation seem to alter hepatocyte Ca 2+ homeostasis after hemorrhagic shock and resuscitation.