1-3-dimethylthiourea and Burns

We found that rats subjected to thermal skin injury (burn) had increased serum hydrogen peroxide (H2O2) scavenging activity, serum catalase activity, erythrocyte (RBC) fragility, and edematous lung injury (lung leak) when compared to sham-treated rats. Serum H2O2 scavenging activity was inhibited by addition of sodium azide, a catalase inhibitor. Treatment of rats with the oxygen radical scavenger, dimethylthiourea (DMTU), decreased RBC fragility and lung leak but did not alter increased H2O2 scavenging or catalase activity of serum from rats subjected to skin burn. We conclude that increased serum catalase activity is a consequence of thermal skin injury and that increased serum catalase activity may be a mechanism that modulates H2O2-dependent processes following skin burn.

Topics: Animals; Burns; Catalase; Erythrocytes; Free Radical Scavengers; Hemolysis; Hydrogen Peroxide; Lung; Permeability; Rats; Skin; Thiourea

Inasmuch as xanthine oxidase (XO)-derived O2* metabolites may contribute to vascular endothelial injury and Factor VIII antigen (F8Ag) is a component of endothelial cells, we hypothesized that XO-derived O2* might damage and cause distant organ endothelial cells to release F8Ag in rats subjected to skin burn. We found that serum F8Ag (ELISA) increased in the blood of rats subjected to skin burn (70 degrees C water to shaved dorsal skin for 30 seconds) but not in sham control rats (30 degrees C water). Coincidentally, F8Ag levels also decreased in lung and kidney tissue sections (immunofluorescent staining) of burned rats but not sham rats. Increases in circulating F8Ag levels and decreases in tissue F8Ag levels appeared to result from XO-derived O2* metabolites: F8Ag levels did not increase in the blood and did not decrease in the tissues of rats pretreated with allopurinol (a specific XO inhibitor, 50 mg/kg) or dimethylthiourea (DMTU) (a permeable O2* metabolite scavenger, 250 mg/kg). Lung injury as assessed by permeability studies (I125-albumin leak) paralleled changes in blood F8Ag levels in sham, burn, allopurinol-, and DMTU-treated groups. We conclude that skin burn causes a systemic vascular injury that can be inhibited by allopurinol or DMTU and is reflected by increased circulating and tissue decreased Factor VIII antigen levels. Release of Factor VIII antigen may serve as a valuable marker of distant organ injury in patients with skin burn.

Topics: Allopurinol; Animals; Antigens; Burns; Capillary Permeability; Endothelium; Factor VII; Kidney; Lung; Male; Osmolar Concentration; Pulmonary Circulation; Rats; Skin; Thiourea; von Willebrand Factor

Previous studies from our laboratory have demonstrated that thermal injury to the skin of rats is associated with the production of oxygen radicals by complement-activated blood neutrophils, resulting in acute lung injury as demonstrated by increases in lung vascular permeability and morphological evidence of vascular endothelial cell damage, interstitial edema, and alveolar hemorrhage. In the present study, the analysis of sera from thermally injured rats reveals an isoenzyme profile for lactate dehydrogenase (LDH;EC 1.1.1.27) that is compatible with origin from lung. The appearance of LDH-4 isoenzyme in serum of thermally injured rats correlates linearly with indices of lung damage, supporting the results of previous studies suggesting that thermal trauma to the skin can cause oxygen radical production by complement-activated blood neutrophils with resultant acute microvascular injury in the lung interstitium. Furthermore, interventions that protect from oxidant-mediated lung injury (catalase, scavengers of hydroxyl radical, iron chelators or neutrophil depletion) result in significant reductions in serum levels of the LDH-4 isoenzyme following thermal injury to the skin. Thus, measurements of LDH isoenzyme patterns in serum appear to be useful in monitoring tissue damage such as oxygen radical-mediated acute lung injury.

Topics: Animals; Burns; Deferoxamine; Free Radicals; Isoenzymes; L-Lactate Dehydrogenase; Lung; Lung Diseases; Lung Injury; Neutrophils; Oxidants, Photochemical; Oxygen; Rats; Rats, Inbred Strains; Skin; Thiourea