ULTRASTRUCTURAL AND BIOCHEMICAL CHANGES IN RENAL MITOCHONDRIA DURING CHRONIC ORAL METHYL MERCURY EXPOSURE - RELATIONSHIP TO RENAL-FUNCTION
ULTRASTRUCTURAL AND BIOCHEMICAL CHANGES IN RENAL MITOCHONDRIA DURING CHRONIC ORAL METHYL MERCURY EXPOSURE - RELATIONSHIP TO RENAL-FUNCTION
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DOI：
10.1016/0014-4800(77)90010-7
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发表时间：
1977-01-01
影响因子：
3.6
通讯作者：
WOODS, JS
中科院分区：
文献类型：
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作者：
FOWLER, BA;WOODS, JS
慢性口服甲基给药对肾小管细胞线粒体的影响与肾功能和卟啉尿与长期甲基汞暴露相关的标准试验描述。雄性大鼠连续6周饮用含有0、3、5或10 ppm汞的甲基氢氧化汞（MMII）的饮用水。电镜观察到肾近端小管细胞线粒体原位肿胀与皮质线粒体呼吸控制比降低有关。位于线粒体外膜的单胺氧化酶的比活性在mmh处理的动物中显示出剂量相关的降低。细胞色素氧化酶作为线粒体内膜的标记酶，其比活性下降较为温和。相比之下，在血红素生物合成途径中的限速酶- δ -氨基乙酰丙酸合成酶与线粒体内膜松散结合，其比活性增加了2- 2.5倍。作为线粒体基质标记酶的苹果酸脱氢酶活性没有变化。上述结果与mmh处理动物尿液中血红素前体浓度升高有关，但血液尿素氮、血清肌酐值或尿中溶菌酶排泄量增加没有变化。这些结果讨论了MMH对肾线粒体膜影响的特异性，以及这些影响在临床毒性发作前评估汞暴露的生物反应中的潜在效用。
The effects of chronic oral methyl administration on renal tubule cell mitochondria in relation to standard tests of renal function and porphyrinuria associated with prolonged methyl mercury exposure are described. Male rats were given access to drinking water containing 0, 3, 5 or 10 ppm Hg as methyl mercuric hydroxide (MMII) for 6 wk. In situ swelling of renal proximal tubule cell mitochondria observed by EM was associated with decreases in respiratory control ratios of cortical mitochondria. The specific activity of monoamine oxidase, which is localized on the outer mitochondrial membrane, showed a dose-related decrease in MMH-treated animals. Cytochrome oxidase, which was used as a marker enzyme for the inner mitochondrial membrane, showed a more moderate decrease in specific activity. In contrast, .delta.-aminolevulinic acid synthetase, which is loosely bound to the inner mitochondrial membrane and is the rate-limiting enzyme in the heme biosynthetic pathway, showed a 2- to 2.5-fold increase in specific activity. Malate dehydrogenase, which was used as a marker enzyme for the mitochondrial matrix, showed no change in activity. The above findings were associated with elevated concentrations of heme precursors in the urine of MMH-treated animals, but no changes in blood urea nitrogen, serum creatinine values, or increased urinary excretion of lysozyme. These results are discussed in regard to the specificity of the effects of MMH on renal mitochondrial membranes and the potential utility of these effects in the assessment of biological responses to Hg exposure prior to the onset of overt clinical toxicity.