Grant M H, Rodger I W
Department of Physiology and Pharmacology, Strathclyde University, Glasgow, UK.
Pulm Pharmacol. 1991;4(3):165-9. doi: 10.1016/0952-0600(91)90007-p.
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.
在致敏豚鼠肺中，白三烯（LT）代谢发生改变，导致LTD4合成增加及其分解代谢减少。这可能导致致敏肺中这种强效痉挛原的浓度升高。白三烯可能通过刺激有毒氧物种的形成而引起支气管平滑肌的高反应性。因此，在致敏肺组织中测量了负责解毒活性氧代谢产物的酶的活性。致敏肺中超氧化物歧化酶活性降低。非硒依赖性谷胱甘肽过氧化物酶的活性增加，而过氧化氢酶、谷胱甘肽还原酶和硒依赖性谷胱甘肽过氧化物酶的活性未受影响。由于这些改变，致敏豚鼠肺可能对超氧化物的作用更敏感，但能够更有效地解毒任何由此产生的脂质过氧化产物。致敏豚鼠肺中的细胞色素P450含量和相关混合功能氧化酶（MFO）系统的活性显著降低。这将导致花生四烯酸代谢改变，特别是环氧二十碳三烯酸的生成，终止半胱氨酰白三烯作用的能力降低，以及外源性物质代谢能力受损。
