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

J Trauma. 2000 Aug;49(2):291-6; discussion 296-7. doi: 10.1097/00005373-200008000-00017.

Abstract

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.

Conclusion: Iron-catalyzed oxyradical production and membrane peroxidation seem to alter hepatocyte Ca2+ homeostasis after hemorrhagic shock and resuscitation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Deferoxamine / pharmacology*
  • Disease Models, Animal
  • Hemodynamics / drug effects
  • Hydroxyethyl Starch Derivatives / pharmacology*
  • Iron Chelating Agents / pharmacology*
  • Lipid Peroxidation / drug effects
  • Liver / cytology
  • Liver / drug effects*
  • Liver / metabolism
  • Male
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Rehydration Solutions / pharmacology*
  • Reperfusion Injury / prevention & control
  • Resuscitation
  • Shock, Hemorrhagic / blood
  • Shock, Hemorrhagic / therapy*

Substances

  • Hydroxyethyl Starch Derivatives
  • Iron Chelating Agents
  • Rehydration Solutions
  • hydroxyethyl starch-deferoxamine conjugate
  • Deferoxamine
  • Calcium