Verschoyle R D, Dinsdale D
MRC Toxicology Unit, Medical Research Council Laboratories, Carshalton Surrey, UK.
Environ Health Perspect. 1990 Apr;85:95-100. doi: 10.1289/ehp.85-1568337.
Protection afforded by trialkyl phosphorothionates against the lung injury caused by trialkyl phosphorothiolates probably results from the inhibition by the P = S moiety of the thionates, of one or more pulmonary cytochrome P-450 isozymes. The aromatic hydrocarbons p-xylene and pseudocumene also protect against this injury and inhibit some P-450 isozymes, but by a different mechanism. OOS-Trimethylphosphorothionate and p-xylene were compared as protective agents against the effect of OOS-trimethylphosphorothiolate and two other lung toxins ipomeanol and 1-nitronaphthalene that are known to be activated by cytochrome P-450. The effects of these protective compounds, in vivo, on pulmonary cytochrome P-450 activity were also determined. Both compounds inhibited pentoxyresorufin O-deethylase activity, but not ethoxyresorufin O-deethylase. The phosphorothionate was most effective against lung injury caused by the phosphorothiolates and 1-nitronaphthalene, whereas p-xylene was much more effective against ipomeanol. beta-Naphthoflavone, which induces pulmonary ethoxyresorufin O-deethylase activity, did not protect against phosphorothiolate or 1-nitronaphthalene injury, and it was only marginally effective in decreasing the toxicity of ipomeanol.
硫代磷酸三烷基酯对硫醇磷酸三烷基酯所致肺损伤的保护作用可能源于硫代磷酸酯的P = S部分对一种或多种肺细胞色素P - 450同工酶的抑制。芳烃对二甲苯和连三甲苯也可预防这种损伤并抑制某些P - 450同工酶，但作用机制不同。比较了硫代磷酸三甲基酯和对二甲苯作为保护剂对抗硫醇磷酸三甲基酯以及另外两种已知由细胞色素P - 450激活的肺毒素异戊间二烯醇和1 - 硝基萘的作用。还测定了这些保护化合物在体内对肺细胞色素P - 450活性的影响。两种化合物均抑制戊氧基试卤灵O - 脱乙基酶活性，但不抑制乙氧基试卤灵O - 脱乙基酶活性。硫代磷酸酯对硫醇磷酸酯和1 - 硝基萘所致肺损伤最有效，而对二甲苯对异戊间二烯醇更有效。诱导肺乙氧基试卤灵O - 脱乙基酶活性的β - 萘黄酮不能预防硫醇磷酸酯或1 - 硝基萘损伤，且在降低异戊间二烯醇毒性方面仅略有效果。
