Reactive oxygen species and endotoxic shock: effect of dimethylthiourea

The effects of endotoxemia on the cardiac function and contractility, oxygen radical production by polymorphonuclear leukocytes (PMNL-CL), cardiac antioxidant reserve (LV-CL), antioxidant enzymes (superoxide dismutase [SOD], catalase, glutathione peroxidase [GSH-P(X)]) and malondialdehyde (MDA); and plasma creatine kinase (CK) and lactate in the absence or presence of dimethylthiourea (DMTU), an antioxidant, in anesthetized dogs were studied. Dogs were assigned to three groups: group 1, control; group II, endotoxin (ET) (5 mg/kg body wt intravenously), and group III, ET + DMTU (500 mg/kg intravenously). ET produced decreases in the cardiac function and contractility, antioxidant reserve, antioxidant enzymes; and increases in PMNL-CL, cardiac MDA, plasma CK, and lactate. Pretreatment with DMTU attenuated the ET-induced cardiac dysfunction and changes in the cardiac MDA, antioxidant reserve, and antioxidant enzymes, PMNL-CL, and plasma CK and lactate levels. These results suggest that reactive oxygen species may be involved in the deterioration of cardiac function and contractility, and cellular injury during endotoxic shock and that antioxidants may be of value in the treatment of endotoxic shock.