Endotoxin causes neutrophil-independent oxidative stress in rats

Endotoxin-induced oxidative stress is investigated in rats by measuring changes in plasma and lung tissue levels of glutathione disulfide (GSSG) using a modified enzymatic assay that allows simultaneous measurement of up to 80 samples. Salmonella enteritidis endotoxin (2 and 20 mg/kg) acutely increased both plasma reduced glutathione and GSSG with a rise in the ratio of GSSG to total glutathione. This increase in GSSG was enhanced by pretreatment with 1,3-bis(2-chloroethyl)1-nitrosourea (BCNU), an inhibitor of the glutathione reductase enzyme. However, there was no significant arteriovenous difference in plasma GSSG across the lung, and lung tissue GSSG did not increase after endotoxin treatment. The increase in plasma GSSG was not blocked by vinblastine-induced neutropenia and could not be reproduced by incubating rat blood in vitro with endotoxin. Receptor antagonists of platelet-activating factor (PAF), at a dose that previously inhibited endotoxin-induced lung injury, attenuated the endotoxin-induced increase in plasma GSSG. We conclude that endotoxin causes neutrophil-independent oxidative stress in rats, which may be enhanced by the action of platelet-activating factor.