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Effects of Heavy Metals on the Heme Metabolism in the Hematopoietic Organ and the Drug-metabolizing Systems in Liver

重金属对造血器官血红素代谢及肝脏药物代谢系统的影响

基本信息

批准号：
62480174
负责人：
MIURA Hajime
金额：
$ 3.78万
依托单位：
Kumamoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1987
资助国家：
日本
起止时间：
1987 至 1988
项目状态：
已结题

项目摘要

Several authors have reported signs of liver or bone marrow dysfunction in lead poisoning. To clarify the effects of lead on the liver or bone marrow, male Wistar rats (about 250g) were treated with lead intraperitoneally at O(the control), 10 and 50mg/kg for 3 days. After the last injection, the rats were starved for 20 hrs and then sacrificed by decapitation, and the effects of lead treatment on the hepatic functions were determined. We administered other porphogenic chemicals such as diphenyl hydantoine (DPH), methyl n-butyl ketone (MBK) and methyl ethyl ketone (MEK) into rats to compare the lead effect on liver or bone marrow. It was found that lead induced a four-fold increase in the activity of heme oxygenase (HO) in the 50mg/kg group than the control but decreased the contents of cytochrome P-450, cytochrome b_5, heme and the activites of drug metabolizing enzymes in liver. The FEP and serum GPT and bilirubin of the lead treated groups did not differ from those of the control group. The EFP, however, increased in the rats. MBK increased the activities of drug metabolizing enzymes and cytochrome P-450 and cytochrome b_5 contents in liver microsome. MEK enhenced the effects of MBK on drug metabolizing enzymes. On the point of FEP unitages for evaluating anemia, FEP mu/g Hb was the most useful than the other units such as, mug/dl.pcv,mug/g-heme,mug/dl.Our present study lead us to form the following hypotheses; lead induces a high activity of HO, and this may be one factor involved in the decreases of heme and cytochrome P-450 by lead.We are now separating the lead binding protein in erythrocyte membrane in lead poisoned animals to clarify its chemical forms in vivo. This may be important to clarify the developing mechanisum of lead toxicity, especially in lead transport into cells and its inactivation in vivo.

一些作者已经报道了铅中毒的肝脏或骨髓功能障碍的迹象。为了弄清铅对肝脏或骨髓的影响，将雄性Wistar大鼠（约250g）按0（对照组）、10和50mg/kg的剂量腹腔注射铅3天。末次注射后，大鼠饥饿20 h后斩首处死，测定铅处理对肝功能的影响。我们给大鼠注射其他致卟啉化学物质，如二苯基苯胺（DPH）、甲基正丁基酮（MBK）和甲基乙基酮（MEK），比较它们对肝脏和骨髓的铅效应。结果表明，50mg/kg铅组小鼠肝脏中血红素加氧酶（HO）活性比对照组升高4倍，细胞色素P-450、细胞色素b_5、血红素含量及药物代谢酶活性均降低。铅处理组FEP、血清GPT和胆红素与对照组无显著差异。然而，大鼠的EFP却增加了。MBK提高了肝微粒体药物代谢酶活性和细胞色素P-450和细胞色素b_5含量。MEK增强了MBK对药物代谢酶的影响。在评价贫血的FEP单位上，FEP mu/g Hb比其他单位如mug/dl.pcv、mug/g-heme、mug/dl最有用。我们目前的研究使我们形成以下假设；铅诱导高HO活性，这可能是铅降低血红素和细胞色素P-450的一个因素。我们目前正在分离铅中毒动物红细胞膜中的铅结合蛋白，以阐明其在体内的化学形态。这可能对阐明铅毒性的发生机制，特别是铅在细胞内的转运及其在体内的失活具有重要意义。