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

几位作者报告了铅中毒导致肝脏或骨髓功能障碍的迹象。为明确铅对大鼠肝脏和骨髓的影响，雄性Wistar大鼠(约250g)按0、10、50 mg/kg剂量连续3天灌胃染毒。最后一次注射后，饥饿20小时，断头处死，观察染铅对大鼠肝功能的影响。为了比较铅对肝脏或骨髓的影响，我们给大鼠注射了其他致血化学物质，如二苯基海因(DPH)、甲基正丁基酮(MBK)和甲乙基酮(MEK)。结果表明，染铅50 mg/kg组小鼠肝组织细胞色素P-450、细胞色素b_5、血红素含量及药物代谢酶活性降低，而血红素加氧酶(HO)活性较对照组升高4倍。染铅组大鼠FEP、血清GPT、胆红素与对照组无明显差异。然而，大鼠的EFP增加了。MBK能提高药物代谢酶活性及肝微粒体细胞色素P-450和细胞色素b5的含量。MEK可增强MBK对药物代谢酶的影响。在评价贫血的FEP单位上，FEPu/g Hb是最有用的单位，如：MUG/dl.pcv，MUG/g-Hb，MUG/dl。我们的研究提出了以下假设：铅诱导HO活性升高，这可能是铅降低血红素和细胞色素P-450的因素之一。我们正在分离铅中毒动物红细胞膜上的铅结合蛋白，以阐明其在体内的化学形态。这可能对阐明铅中毒的发展机制，特别是体内铅向细胞的转运及其失活具有重要意义。

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.