Pyruvate prevents poly-ADP ribose polymerase (PARP) activation, oxidative damage, and pyruvate dehydrogenase deactivation during hemorrhagic shock in swine.
The inadequate availability of fuel substrates and sharp decline in cellular ATP have been implicated in a cascade of events associated with cell death and organ failure during hemorrhagic shock (HS). In this in vivo swine model of severe prolonged HS, the effect of exogenous pyruvate administration on various markers of cell damage in brain and liver was examined. Thirty minutes after the start of controlled arterial hemorrhage, 30% sodium pyruvate, 10% saline, or 0.9% saline was administered via jugular vein. Four hours after the initiation of hemorrhage, tissue samples from brain and liver were obtained and examined for the cellular and molecular markers of cellular damage. Results of our study suggest that pyruvate prevents loss of total NAD content, cleavage of poly-ADP ribose polymerase (PARP), and inhibits lipid peroxidation in both the brain and liver of swine during prolonged severe HS. We conclude that there are multiple mechanisms by which pyruvate can possibly prevent cell damage caused during HS.
Mongan
Paul D
PD
Department of Anesthesiology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA. pmongan@usuhs.mil
Karaian
John
J
Van Der Schuur
Brian M
BM
Via
Darin K
DK
Sharma
Pushpa
P
D000818:Animals; D001921:Brain / Q000378:metabolism; D007658:Ketone Oxidoreductases / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D023421:Models, Animal; D018384:Oxidative Stress / Q000502:physiology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D019289:Pyruvic Acid / Q000378:metabolism*; D012771:Shock, Hemorrhagic / Q000378:metabolism*; D013552:Swine
D019289:Pyruvic Acid; D007658:Ketone Oxidoreductases; C053164:pyruvate dehydrogenase (NADP+); D011065:Poly(ADP-ribose) Polymerases