Effect of aging, sex and diet on biotransformation of methylmercury

1.甲基汞生物转化的活性氧物种和细胞内部位的鉴定甲基汞的生物转化。在孵育4h期间，脑片中无机汞的形成呈时间依赖性。在百草枯的存在下，脱甲基化速度大大加快，这表明来自试剂的活性氧物种参与了脱甲基化反应。而产生羟基的催化剂Fe~(2+)和Gt~(2+)对脱甲基化无影响。此外，去铁胺、螯合剂Fe~(2+)、甘露醇、DMSO、OH清除剂对去甲基化也没有影响。这些结果表明，肝脏切片中甲基汞的去甲基化可能是通过超氧阴离子或超氧阴离子自由基的作用而发生的。鱼藤酮(抑制剂复合体I)的存在促进了去甲基化和脂质过氧化，而抗霉素A和NaCN(抑制…)的存在促进了去甲基化和脂质过氧化更多的情结使他们感到沮丧。这些抑制剂对脂质过氧化的抑制作用与以往利用线粒体内膜的实验结果非常相似。对注射甲基汞的大鼠肝脏匀浆进行细胞分级实验，发现线粒体部分中无机汞的比例最高。这些结果表明，甲基汞的生物转化很大一部分是在线粒体内膜进行的，线粒体内膜产生了相当数量的活性氧。2.衰老对甲基汞生物转化的影响。与青年鼠(9周龄)相比，老龄小鼠(40周龄)肝脏中无机汞的产生受到抑制。3.饲料蛋白质含量对甲基汞生物转化的影响。正常蛋白质(14%)、低蛋白(7%)饲料、研究了高蛋白饲料(50%)和普通蛋白质饲料+蛋氨酸(1.6%)对甲基汞生物转化的影响。4组间差异无统计学意义。较少

1.Identification of reactive oxygen species involving in, and of intracellular site of biotransformation of methylmercury.Biotransformation of methylmercury (MeHg) was examined using liver slices prepared from a MeHg-injected rats. Fortmation of inorganic Hg in the slices proceeded in a time-dependent manner during 4 h incubation. The demethylation was drastically accelerated in the presence of paraquat, suggesting participation of reactive oxygen species derived from the reagent. On the other hand, Fe^<2+>, catalyst of OH production, did not affect on the demetylation. Furthermore, deferoxamine, Fe^<2+> chelator, mannitol nor DMSO,OH scavenger, also showed no effect on the demethylation. These results imply that the demethylation of MeHg in the liver slices would occur by the action of a superoxide or superoxide-derived reactive oxygen species beside OH.Presence of rotenone (an inhibitor complex I) enhanced the demethylation and lipid peroxidation, whereas antimycine A and NaCN (inhib … More itor of complex III) depressed them. The depressive effects on the lipid peroxidation of these inhibitors were very similar to the effects found in the previous experiments using mitochondria inner membrane.Cell fractionation experiment of the liver homogenate prepared from MeHg injected rats revealed that the highest ratio of inorganic Hg was found in the mitochondria fraction. Moreover, the inner membrane fraction showed higher inorganic Hg ratio than the whole mitochondria.These results suggest that the significant part of MeHg biotransformation proceeds in the mitochondria inner membrane where quite an amount of reactive oxygen are produced.2.Effect of aging on biotransformation of MeHg.Inorganic Hg production in the liver was depressed in the aged mice (40 weeks of age) as compared with young mice (9 weeks of age).3.Effect of protein contents of diet on biotransformation of MeHg.Effect of normal protein (14%) diet, low protein (7%) diet, high protein (50%) diet and normal protein diet + methionine (1.6%) on biotransformation of MeHg were examined in mice. There were no difference among 4 groups. Less