660
ORGAN, TISSUE, AND CELL DAMAGE
[71]
the triggers of DIC, is released when the endothelium is damaged. Lipid peroxidation mediated by active oxygen species is believed to be one of the important causes of cell membrane destruction and cell damage. The injury to the endothelial cells, platelets, or any kind of tissues may activate the coagulation system. These findings suggest that active oxygen species and lipid peroxidation may play important roles in the thrombus formation induced by endotoxin.
[71] O x y R a d i c a l s in E n d o t o x i n S h o c k
By TOSHIKAZUYOSHIKAWA There is considerable indirect evidence supporting the role of oxygen radicals in circulatory shock.l,2 Endotoxin is a toxin released from dead gram-negative bacteria, and this toxin produces circulatory depression in septicemic patients concomitantly with a variety of other cellular dysfunctions. Exposure to endotoxin can prime neutrophils to increase their release of superoxide, 3 and endotoxin challenge results in superoxide generation in mice at levels that may ultimately result in death. 4
Endotoxin-Induced Shock Experimental shock can be induced by a single injection of 100 mg/kg of endotoxin (Escherichia coli 055:B5 lipopolysaccharide B; Difco Lab., Detroit MI), diluted in 1.0 ml of physiological saline, into the femoral vein using a syringe. Immediately after the injection of endotoxin, systolic blood pressure is reduced and heart rate is increased. Serum acid phosphatase and/3-glucuronidase activities are increased. These changes are greatest at 45 min after the injection of endotoxin. Serum thiobarbituric acid (TBA)-reactive substances are increased, and the serum a-toi T. Yoshikawa, M. Murakami, O. Seto, Y. Kakimi, T. Takemura, T. Tanigawa, S. Sugino, and M. Kondo, J. Clin. Biochem. Nutr. 1, 165 (1986). 2 T. Yoshikawa, O. Seto, K. Itani, Y. Kakimi, S. Sugino, and M. Kondo, in "Oxygen Free Radicals in Shock" (G. P. Novelli and F. Ursini, eds.), p. 125. Karger, Basel, 1986. 3 R. B. Johnson, Jr., L. A. Guthrie, and L. McPhail, in "Oxy Radicals and Their Scavenger Systems" (R. A. Greenwald and G. Cohen, eds.), Vol. 2, p. 69. Elsevier, New York, 1983. 4 B. Gray, Toxicol. Appl. Pharmacol. 60, 479 (1981).
METHODS IN ENZYMOLOGY, VOL. 186
Copyright © 1990 by Academic Press, Inc. All fights of reproduction in any form reserved.
[71]
661
OXY RADICALS IN ENDOTOXIN SHOCK
=6 o~ c v
< 3 0.05 ** 0
ORGAN, TISSUE, AND CELL DAMAGE
[71]
the triggers of DIC, is released when the endothelium is damaged. Lipid peroxidation mediated by active oxygen species is believed to be one of the important causes of cell membrane destruction and cell damage. The injury to the endothelial cells, platelets, or any kind of tissues may activate the coagulation system. These findings suggest that active oxygen species and lipid peroxidation may play important roles in the thrombus formation induced by endotoxin.
[71] O x y R a d i c a l s in E n d o t o x i n S h o c k
By TOSHIKAZUYOSHIKAWA There is considerable indirect evidence supporting the role of oxygen radicals in circulatory shock.l,2 Endotoxin is a toxin released from dead gram-negative bacteria, and this toxin produces circulatory depression in septicemic patients concomitantly with a variety of other cellular dysfunctions. Exposure to endotoxin can prime neutrophils to increase their release of superoxide, 3 and endotoxin challenge results in superoxide generation in mice at levels that may ultimately result in death. 4
Endotoxin-Induced Shock Experimental shock can be induced by a single injection of 100 mg/kg of endotoxin (Escherichia coli 055:B5 lipopolysaccharide B; Difco Lab., Detroit MI), diluted in 1.0 ml of physiological saline, into the femoral vein using a syringe. Immediately after the injection of endotoxin, systolic blood pressure is reduced and heart rate is increased. Serum acid phosphatase and/3-glucuronidase activities are increased. These changes are greatest at 45 min after the injection of endotoxin. Serum thiobarbituric acid (TBA)-reactive substances are increased, and the serum a-toi T. Yoshikawa, M. Murakami, O. Seto, Y. Kakimi, T. Takemura, T. Tanigawa, S. Sugino, and M. Kondo, J. Clin. Biochem. Nutr. 1, 165 (1986). 2 T. Yoshikawa, O. Seto, K. Itani, Y. Kakimi, S. Sugino, and M. Kondo, in "Oxygen Free Radicals in Shock" (G. P. Novelli and F. Ursini, eds.), p. 125. Karger, Basel, 1986. 3 R. B. Johnson, Jr., L. A. Guthrie, and L. McPhail, in "Oxy Radicals and Their Scavenger Systems" (R. A. Greenwald and G. Cohen, eds.), Vol. 2, p. 69. Elsevier, New York, 1983. 4 B. Gray, Toxicol. Appl. Pharmacol. 60, 479 (1981).
METHODS IN ENZYMOLOGY, VOL. 186
Copyright © 1990 by Academic Press, Inc. All fights of reproduction in any form reserved.
[71]
661
OXY RADICALS IN ENDOTOXIN SHOCK
=6 o~ c v
< 3 0.05 ** 0
