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

Background: This study investigated whether hepatocyte Ca2+ dysregulation a fter hemorrhagic shock and resuscitation could be modulated by the iron che lator 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-b lood volume as lactated Ringer's solution, 1 mt of pentastarch solution (hy droxyethyl starch 10%) per mt of shed blood, or 1 mt of HES-DFO solution (1 0%) per mt of shed blood. In isolated hepatocytes, the rate of Ca2+ influx (Ca(2+)in), total Ca2+ uptake (Ca(2+)up), and membrane Ca2+ flux (Ca(2+)flu x) were determined by Ca-45 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 decr eased 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 Ca2+ homeostasis after hemorrhagic shock and resus citation.