The metabolism of leukotrienes, detoxification of reactive oxygen species and the activity of the cytochrome P450 mixed function oxidase system in sensitised guinea-pig lungs

In sensitised guinea-pig lungs alterations in leukotriene (LT) metabolism occurred which resulted in an increase in LTD4 synthesis and a reduction in its catabolism. This may lead to an increase in the concentration of this potent spasmogen in the sensitised lungs. The LTs may cause hyperreactivity of bronchial smooth muscle by stimulating formation of toxic oxygen species. Thus, the activities of the enzymes responsible for detoxifying reactive oxygen metabolites were measured in the sensitised lung tissue. Superoxide dismutase activity was decreased in sensitised lungs. The activity of the selenium-independent glutathione peroxidase was increased, whereas those of catalase, glutathione reductase and the selenium-dependent glutathione peroxidase were unaffected. As a result of these alterations, sensitised guinea pig lungs may be more sensitive to the effects of superoxide, but are able to detoxify the products of any resulting lipid peroxidation more efficiently. The cytochrome P450 content of the lung and the activity of the associated mixed function oxidase (MFO) system was significantly decreased in sensitised guinea-pigs. This will lead to altered arachidonate metabolism, particularly generation of epoxyeicosatrienoic acids, decreased capacity to terminate the action of cysteinyl LTs and also compromised xenobiotic metabolising ability.