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Pyruvate modulates hepatic mitochondrial functions and reduces apoptosis indicators during hemorrhagic shock in rats.

AbstractBACKGROUND:
Dysfunctional mitochondria have been widely accepted as one of the key targets and a mediator of secondary cell injury and organ failure during hemorrhagic shock (HS). The liver is known to be the first organ to display the signs of injury during HS. This report describes experiments to determine whether modulation of hepatic mitochondrial dysfunctions by pharmacologic agents could prevent liver injury in rats subjected to HS.
METHODS:
In this study, Sprague-Dawley rats were either treated as controls or subjected to computer-controlled arterial hemorrhage (40 mmHg) for 60 min followed by resuscitation with hypertonic saline, hypertonic beta-hydroxybutyrate, or hypertonic sodium pyruvate for the next 60 min before death. During the course of the experiment, animals were continuously monitored for hemodynamic and metabolic parameters. At the end of the experiment, the liver was excised and examined for oxidative injury, mitochondrial functions, expression of nitric oxide synthase, and indicators of apoptosis.
RESULTS:
In comparison to hypertonic saline and hypertonic beta-hydroxybutyrate, pyruvate significantly protected the liver from oxidative injury, prevented the up-regulation of nitric oxide synthase, inhibited pyruvate dehydrogenase deactivation, and improved cellular energy charge and mitochondrial functions. In addition, pyruvate also reduced cleavage of poly-adenosine diphosphate ribose polymerase by preventing leakage of mitochondrial cytochrome c in the liver of HS animals.
CONCLUSIONS:
These data suggest that modulation of mitochondrial metabolic functions is likely to be one of the important mechanisms by which pyruvate exerts its protective effects on the liver during HS and resuscitation in rats.
AuthorsPushpa Sharma, Kane T Walsh, Kimberly A Kerr-Knott, John E Karaian, Paul D Mongan
JournalAnesthesiology (Anesthesiology) Vol. 103 Issue 1 Pg. 65-73 (Jul 2005) ISSN: 0003-3022 [Print] United States
PMID15983458 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References
  • Pyruvic Acid
Topics
  • Animals
  • Apoptosis (drug effects, physiology)
  • Male
  • Mitochondria, Liver (drug effects, metabolism)
  • Pyruvic Acid (pharmacology, therapeutic use)
  • Rats
  • Rats, Sprague-Dawley
  • Shock, Hemorrhagic (metabolism, prevention & control)

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