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Relationship between liver oxidant stress and antioxidant activity after zymosan peritonitis in the rat
C LaLonde1, R Daryani, C Campbell
1Longwood Area Trauma Center, Brigham and Women's Hospital.
Objective:
To determine the effect of a severe nonbacterial-dependent peritonitis on the degree and time course of liver oxidant stress and antioxidant activity.
Design:
Prospective, randomized, controlled study.
Setting:
Animal laboratory.
Subjects:
Thirty-eight male Sprague-Dawley rats were injected with zymosan 0.75 mg/g body weight, mixed in mineral oil, and fluid resuscitated.
Interventions:
None.
Measurements And Main Results:
Oxygen consumption (VO2), base deficit, and blood gases were determined. Liver tissue oxidized and reduced glutathione, malondialdehyde catalase, xanthine oxidase, and xanthine dehydrogenase were measured and data were compared with both a pair-fed and an ad libitum fed group over a 24-hr period. We noted a 30% mortality rate with animals dying between 20 and 24 hrs. Peak decrease in VO2 occurred at 12 hrs, corresponding with a metabolic acidosis. Marked liver oxidant stress was seen at 4 hrs with oxidized glutathione increased from a control value of 0.2 +/- 0.1 to 1.1 +/- 0.2 mg/g of tissue, while reduced glutathione decreased from a control value of 1.8 +/- 0.1 to 0.3 +/- 0.1 mg/g. By 24 hrs, oxidized glutathione activity was no longer increased, but reduced glutathione concentrations were still markedly decreased. Tissue catalase was also significantly decreased at the 24-hr period. Liver malondialdehyde was increased at 24 hrs when the peak decrease in antioxidants was evident. Liver xanthine oxidase activity increased significantly from 15 +/- 3 to 45 +/- 8 mumol uric acid/min/g by 4 hrs and remained increased, with the initial increase predating evidence of impaired perfusion. Pair-fed animals demonstrated no changes in oxidant or antioxidant activity.
Conclusions:
We conclude that a marked increase in liver oxidant stress and decrease in antioxidant activity occurs in the first several hours after the onset of nonbacterial peritonitis. An early increase in liver xanthine oxidase activity may be a source of the oxidants. Decreased liver antioxidant activity persists well after the oxidant stress resolves.