ZINC-PROTOPORPHYRIN IS A SELECTIVE INHIBITOR OF HEME OXYGENASE ACTIVITY IN THE NEONATAL RAT
ZINC-PROTOPORPHYRIN IS A SELECTIVE INHIBITOR OF HEME OXYGENASE ACTIVITY IN THE NEONATAL RAT
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DOI:
10.1016/0304-4165(81)90465-7
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发表时间:
1981-01-01
期刊:
影响因子:
--
通讯作者:
MAINES, MD
中科院分区:
文献类型:
--
作者:
MAINES, MD
The liver, spleen and kidney heme oxygenase activity in the rat was examined and the response of the enzyme to a variety of metalloporphyrin complexes was investigated. The enzyme activity in the liver and the kidney of 3-4 day old rats was several-fold greater than the corresponding values in the adult animals; the splenic enzyme activity was markedly depressed in comparison to that of adult rats. During the first 2-3 wk post-parturation period, the activity of heme oxygenase in the spleen progressively increased, and in 4 wk approached the adult values. The treatment of the newborn animals with the metalloporphyrin complex, Zn.cntdot.protoporphyrin-IX, inhibited heme oxygenase activity in the spleen, liver and the kidney. Sn.cntdot.protoporphyrin treatment also inhibited the activity of the enzyme in the liver and the spleen. The mechanism of the inhibition appeared to be competitive in nature. In contrast, the treatment of the newborn animals with Co.cntdot.protoporphyrin increased the activity of the enzyme in the tested organs. The treatment of newborn animals with Fe.cntdot.protoporphyrin (heme) also increased heme oxygenase activity in the spleen and the kidney. In addition, Co.cntdot. and Fe.cntdot.protoporphyrin complexes inhibited the activity of .delta.-aminolevulinate synthetase in the spleen; Sn.cntdot.protoporphyrin and Zn.cntdot.protoporphyrin did not alter the activity of this enzyme. The effects of Co.cntdot.protoporphyrin and Zn.cntdot.protoporphyrin on the microsomal contents of cytochromes P-450, b5, the total heme, and the microsomal drug metabolism activity in the liver were compared. Zn.cntdot.protoporphyrin was ineffective in altering the indicated cellular variables. According to these findings Zn.cntdot.protoporphyrin may be useful as an experimental tool for the selective suppression of heme degradation activity.