diethyl-maleate and Lung-Diseases

Systemic ischaemia-reperfusion (IR) injury is in part an oxidant injury mediated by neutrophils. Diethylmaleate (DEM), an intracellular pro-oxidant agent, has been shown to alleviate neutrophil-mediated tissue injury. The aim of this study was to evaluate whether DEM could have a protective effect on neutrophil-mediated lung injury in an animal model of lower-torso IR.. Sprague-Dawley rats (seven per group) were randomized into three groups. The control group underwent midline laparotomy only; the IR group underwent laparotomy and clamping of the infrarenal abdominal aorta for 30 min followed by 2 h of reperfusion; and the third group was pretreated with DEM 6 mmol/kg intraperitoneally 1 h before the IR insult.. IR resulted in a significant increase in both microvascular leakage and pulmonary neutrophil infiltration as measured by bronchoalveolar lavage protein concentration and pulmonary myeloperoxidase activity respectively. Pretreatment with DEM significantly attenuated both microvascular leakage and neutrophil infiltration.. Preconditioning with DEM protected against IR-induced lung injury. This protective effect raises the possibility of using pro-oxidants to prevent inflammatory injury.

Topics: Animals; Aorta; Constriction; Lung; Lung Diseases; Male; Maleates; Microcirculation; Neutrophils; Oxidants; Rats; Rats, Sprague-Dawley; Reperfusion Injury

The relative roles of tissue glutathione and vitamin E concentrations in the pneumotoxicity of 3-methylindole were studied. Thirty-two goats were divided into four groups and pretreated with (i) vitamin E + cysteine, (ii) vitamin E + diethylmaleate, (iii) cysteine, and (iv) diethylmaleate to vary tissue concentrations of glutathione and (or) vitamin E. Lung tissue concentrations of glutathione, vitamin E, and cytochrome P-450 were measured after pretreatments in four of eight animals in each group. Groups pretreated with cysteine had higher glutathione levels in the lung than those of diethylmaleate-pretreated goats. Goats receiving vitamin E had significantly higher concentrations of vitamin E than unsupplemented groups. After pretreatments the other four goats in each group were challenged with 3-methylindole (0.03 g/kg body weight) by intrajugular infusion. The severity of lung lesions was evaluated and scored by gross and microscopic examination at 72 h after infusion. 3-Methylindole-induced lung lesions were severe when tissue glutathione was reduced and were mild when tissue glutathione was induced. Enhancement of tissue vitamin E did not significantly affect 3-methylindole toxicity. These results indicate that the initial toxicological event is likely to be the result of binding of 3-methylindole free radical covalently to cellular protein rather than lipid peroxidation.

Topics: Animals; Cysteine; Glutathione; Goats; Indoles; Lung; Lung Diseases; Male; Maleates; Organ Size; Skatole; Vitamin E

The effects of t-butylhydroperoxide (TBH) and cigarette smoke on lung mechanics (CDYN and RL) and glutathione status (GSH) were studied using an isolated perfused and ventilated rat lung preparation. TBH (200, 400, 1000 microM) infused via the pulmonary circulation caused a dose-related bronchoconstriction. The lung GSH-levels were also significantly reduced. Pretreatment of rats with diethylmaleate (DEM) potentiated the TBH elicited bronchoconstriction. DEM (1 mM) infused into the pulmonary circulation caused an almost complete depletion of GSH-content but no effects on lung mechanics were seen. Indomethacin (2.8 and 28 microM) infusion attenuated TBH (400 microM) induced bronchoconstriction. These findings suggest that the TBH induced bronchoconstriction is at least partly mediated via arachidonic acid metabolites. When TBH was administered intratracheally, weak and not dose-related bronchoconstriction was observed even though doses higher than those given intravascularly were used. However, the GSH-content of the lungs was markedly decreased. Cigarette smoke caused weak if any effects on lung mechanics but significantly decreased lung GSH-content.

Topics: Animals; Bronchi; Constriction, Pathologic; Drug Synergism; Glutathione; Indomethacin; Lung; Lung Diseases; Male; Maleates; Nicotiana; Peroxides; Plants, Toxic; Rats; Rats, Inbred Strains; Smoke; tert-Butylhydroperoxide

Topics: Animals; Chemical and Drug Induced Liver Injury; Cyclohexanes; Cyclohexanones; Glutathione; Lung Diseases; Male; Maleates; Mice; Mice, Inbred BALB C; Oils, Volatile; Terpenes; Time Factors