Effects of Heavy Metals on the Heme Metabolism in the Hematopoietic Organ and the Drug-metabolizing Systems in Liver
| Project/Area Number |
62480174
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Hygiene
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| Research Institution | Kumamoto University |
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Principal Investigator |
MIURA Hajime Department of Hygiene Kumamoto University Medical School, 医学部 (00039489)
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| Co-Investigator(Kenkyū-buntansha) |
OMORI Shoko Department of Hygiene Kumamoto University Medical School, 医学部, 助手 (60040193)
HARADA Koichi Department of Hygiene Kumamoto University Medical School, 医学部, 講師 (00094029)
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| Project Period (FY) |
1987 – 1988
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| Project Status |
Completed (Fiscal Year 1988)
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| Budget Amount *help |
¥5,900,000 (Direct Cost: ¥5,900,000)
Fiscal Year 1988: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1987: ¥4,900,000 (Direct Cost: ¥4,900,000)
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| Keywords | Heavy Metal / Lead / Drug metabolism in liver / Heme pathway / Cytochrome P450 / 赤血球遊離プロトポルフィリン / ヘムオキシゲナーゼ / チトクロームP450 |
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| Research Abstract |
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.
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Report
(3 results)
Research Products
(9 results)
