EFFECTS OF HYDROGEN-SULFIDE EXPOSURE ON LUNG MITOCHONDRIAL RESPIRATORY-CHAIN ENZYMES IN RATS
EFFECTS OF HYDROGEN-SULFIDE EXPOSURE ON LUNG MITOCHONDRIAL RESPIRATORY-CHAIN ENZYMES IN RATS
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DOI：
10.1016/0041-008x(90)90321-k
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发表时间：
1990-05-01
影响因子：
3.8
通讯作者：
LILLIE, LE
中科院分区：
文献类型：
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作者：
KHAN, AA;SCHULER, MM;LILLIE, LE
将fisher -344大鼠暴露于不同浓度的硫化氢（H2S）气体中4小时，并在暴露后立即或1、24或48小时杀死。测定肺组织线粒体组分呼吸链酶活性。暴露于低浓度（10ppm） H2S对大鼠肺线粒体酶活性无显著影响。然而，暴露于亚致死浓度的H2S （50-400 ppm）会显著降低呼吸链细胞色素c氧化酶和琥珀酸氧化酶复合物的活性。在急性暴露于>500 popm H2S的大鼠中，肺细胞色素氧化酶活性的抑制最严重（>90%）。在暴露于200和400 ppm H2S的大鼠中，暴露后24和48小时观察到肺部细胞色素c氧化酶活性明显恢复。对大鼠肺线粒体的体外研究表明，低浓度硫化物对细胞色素c氧化酶活性也有类似的选择性抑制作用。通过洗涤或用高铁血红蛋白氧化去除硫化物后，这种作用被逆转。与铁细胞色素c相比，硫化物对细胞色素c氧化酶的抑制作用是非竞争性的。由于nadh -细胞色素c还原酶和琥珀酸-细胞色素c还原酶的活性在H2S暴露和低浓度硫化物的体外处理下没有显著改变，因此我们得出结论，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（组织毒性）缺氧。
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 oxidase activity in lungs was most severe (>90%) in rats that died from acute exposure to >500 popm 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.