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

几位作者报道了铅中毒时肝脏或骨髓功能障碍的迹象。为探讨铅对肝脏和骨髓的影响，雄性Wistar大鼠（体重约250 g）连续3天腹腔注射0（对照组）、10和50 mg/kg铅。最后一次注射铅后，将大鼠饥饿20小时，然后断头处死，测定铅处理对肝功能的影响。我们给大鼠注射了其他致形态学物质，如二苯基海因（DPH）、甲基正丁基酮（MBK）和甲基乙基酮（MEK），以比较铅对肝脏或骨髓的影响。结果表明，铅50 mg/kg组大鼠肝脏血红素氧合酶（HO）活性比对照组增加4倍，而细胞色素P-450、细胞色素b_5、血红素含量及药物代谢酶活性均降低。染铅组的FEP、血清GPT和胆红素与对照组无差异。然而，EFP在大鼠中增加。MBK可提高肝微粒体药物代谢酶活性和细胞色素P-450、细胞色素b_5含量。MEK可增强MBK对药物代谢酶的作用。就FEP单位评价贫血而言，FEP μ/g Hb比其它单位如μ g/dl、pcv、μ g/g-血红素、μ g/dl更有用。铅诱导HO的高活性，这可能是血红素和细胞色素P-我们正在分离铅中毒动物红细胞膜上的铅结合蛋白，以明确其在体内的化学形态。这对阐明铅毒性的形成机制，特别是铅在体内的细胞转运和失活机制可能具有重要意义。

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.