Glutathione deficiency increases organ dysfunction after hemorrhagic shock.
BACKGROUND
Reactive oxygen metabolites contribute to tissue destruction in a wide variety of diseases. Glutathione, a potent endogenous antioxidant, neutralizes the destructive potential of free radicals, but this tripeptide may be depleted during illness. We hypothesized that glutathione deficiency would amplify organ dysfunction after shock in rats.


METHODS
Rats received either diethyl maleate to deplete tissue glutathione or a control solution intraperitoneally. The animals were subsequently bled to and maintained at a mean arterial pressure of 40 mm Hg for 30 minutes and then fully resuscitated. Sham animals underwent blood pressure monitoring only. Tissue glutathione, liver and renal function tests, organ bacterial content, and mortality rates were determined 4 and 24 hours after shock.


RESULTS
Normal rats subjected to shock and sham animals had similar laboratory chemistry results, organ culture results, and mortality rates. However, glutathione-depleted animals subjected to shock had elevated liver and renal function tests, increased organ bacteria, and a dramatic increase in mortality rates compared with control shock and sham animals.


CONCLUSIONS
We conclude that glutathione deficiency predisposes animals to organ failure and death after an otherwise nonlethal period of hypotension. Because glutathione deficiency is associated with severe injury and sepsis, treatment strategies that maintain glutathione stores may decrease the incidence of multisystem organ failure.
Robinson
M K
MK
Department of Surgery, Brigham and Women's Hospital/Harvard Medical School, Boston, MA 02115.
Rounds
J D
JD
Hong
R W
RW
Jacobs
D O
DO
Wilmore
D W
DW
D000818:Animals; D005978:Glutathione / Q000172:deficiency* / Q000378:metabolism; D006439:Hemodynamics; D007422:Intestines / Q000503:physiopathology*; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology*; D008099:Liver / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D009924:Organ Culture Techniques; D051381:Rats; D011919:Rats, Inbred Strains; D012771:Shock, Hemorrhagic / Q000378:metabolism / Q000401:mortality / Q000503:physiopathology*
D005978:Glutathione