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

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.

• Authors: S Rose, A Pizanis, M Silomon
• Journal: The Journal of trauma (J Trauma) Vol. 49 Issue 2 Pg. 291-6; discussion 296-7 (Aug 2000) ISSN: 0022-5282 [Print] United States
• PMID: 10963542 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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, drug effects, metabolism)
• Male
• Random Allocation
• Rats
• Rats, Sprague-Dawley
• Rehydration Solutions (pharmacology)
• Reperfusion Injury (prevention & control)
• Resuscitation
• Shock, Hemorrhagic (blood, therapy)