Khan A A, Schuler M M, Prior M G, Yong S, Coppock R W, Florence L Z, Lillie L E
Animal Sciences Division, Alberta Environmental Centre, Vegreville, Canada.
Toxicol Appl Pharmacol. 1990 May;103(3):482-90. doi: 10.1016/0041-008x(90)90321-k.
Fischer-344 rats were exposed for 4 hr to various concentrations of hydrogen sulfide (H2S) gas and killed either immediately or at 1, 24, or 48 hr after exposure. Mitochondrial fractions from lung tissues were assayed for the activities of respiratory chain enzymes. Exposure of rats to a low concentration (10 ppm) of H2S caused no significant changes in the activities of lung mitochondrial enzymes. However, exposure to sublethal concentrations of H2S (50-400 ppm) produced marked and highly significant depressions in the activities of cytochrome c oxidase and succinate oxidase complexes of the respiratory chain. The inhibition of cytochrome c oxidase activity in lungs was most severe (greater than 90%) in rats that died from acute exposure to greater than 500 ppm H2S. In rats exposed to 200 and 400 ppm H2S, a marked recovery in cytochrome c oxidase activity of lungs was observed at 24 and 48 hr postexposure. Studies in vitro with rat lung mitochondria showed that low concentrations of sulfide also caused a similar and selective inhibition of cytochrome c oxidase activity. This effect was reversed upon removal of sulfide either by washing or by oxidation with methemoglobin. The nature of sulfide inhibition of cytochrome c oxidase was noncompetitive with respect to ferrocytochrome c. Because the activities of NADH-cytochrome c reductase and succinate-cytochrome c reductase were not significantly altered by H2S exposure and in vitro treatments with low concentrations of sulfide, it is concluded that under physiological conditions H2S would block the respiratory chain primarily by inhibiting cytochrome c oxidase. Such a biochemical impairment would lead to functional (histotoxic) hypoxia in the lung tissues.
将Fischer - 344大鼠暴露于不同浓度的硫化氢（H₂S）气体中4小时，然后在暴露后立即或1、24或48小时处死。测定肺组织线粒体部分呼吸链酶的活性。将大鼠暴露于低浓度（10 ppm）的H₂S中，肺线粒体酶的活性没有显著变化。然而，暴露于亚致死浓度的H₂S（50 - 400 ppm）会导致呼吸链细胞色素c氧化酶和琥珀酸氧化酶复合物的活性显著降低。急性暴露于大于500 ppm H₂S而死亡的大鼠，其肺中细胞色素c氧化酶活性的抑制最为严重（大于90%）。在暴露于200和400 ppm H₂S的大鼠中，暴露后24和48小时观察到肺细胞色素c氧化酶活性有明显恢复。对大鼠肺线粒体进行的体外研究表明，低浓度的硫化物也会对细胞色素c氧化酶活性产生类似的选择性抑制。通过洗涤或用高铁血红蛋白氧化去除硫化物后，这种效应会逆转。硫化物对细胞色素c氧化酶的抑制性质相对于亚铁细胞色素c是非竞争性的。由于H₂S暴露和低浓度硫化物的体外处理对NADH - 细胞色素c还原酶和琥珀酸 - 细胞色素c还原酶的活性没有显著影响，因此得出结论，在生理条件下，H₂S主要通过抑制细胞色素c氧化酶来阻断呼吸链。这种生化损伤会导致肺组织出现功能性（组织中毒性）缺氧。
