Tissue distribution of synthetic heme analogues: Studies with tin, chromium, and zinc mesoporphyrins

被引：11

作者：

Bundock, EA ^{[1
]}

Drummond, GS ^{[1
]}

Kappas, A ^{[1
]}

机构：

[1] ROCKEFELLER UNIV HOSP, NEW YORK, NY 10021 USA

来源：

PHARMACOLOGY | 1996年 / 52卷 / 03期

关键词：

heme oxygenase inhibitor; metalloporphyrin; tissue disposition; brain;

D O I：

10.1159/000139383

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The uptake in tissue of Sn-mesoporphyrin (SnMP), Cr-mesoporphyrin (CrMP) and Zn-mesoporphyrin (ZnMP) administered at doses ranging from 1 to 10 mu mol/kg BW and the effects of these compounds on heme oxygenase activity were examined in both adult and neonatal rats. SnMP and CrMP, but not ZnMP, were rapidly cleared from blood and taken up by liver, spleen and kidney where marked inhibition of heme oxygenase activity was demonstrated. None of the metalloporphyrins were detectable in brain, and no inhibition of heme oxygenase activity was demonstrable in this tissue after administration of the compounds to both adult and neonatal rats. These results demonstrate that SnMP, CrMP and ZnMP do not cross the blood brain barrier, a fact of interest in relation to the potential use of these compounds clinically.

引用

收藏

页码：187 / 198

页数：12

相关论文

共 20 条

[1]

ANDERSON KE, 1984, J PHARMACOL EXP THER, V228, P327

[2] BRAIN 5-AMINOLAEVULINATE SYNTHASE - DEVELOPMENTAL ASPECTS AND EVIDENCE FOR REGULATORY ROLE [J].

DEMATTEIS, F ;

ZETTERLUND, P ;

WETTERBERG, L .

BIOCHEMICAL JOURNAL, 1981, 196 (03) :811-817

[3] CONTROL OF HEME METABOLISM BY SYNTHETIC METALLOPORPHYRINS [J].

DRUMMOND, GS .

ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, 1987, 514 :87-95

[4] PREVENTION OF NEONATAL HYPERBILIRUBINEMIA BY TIN PROTOPORPHYRIN-IX, A POTENT COMPETITIVE INHIBITOR OF HEME OXIDATION [J].

DRUMMOND, GS ;

KAPPAS, A .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1981, 78 (10) :6466-6470

[5] AN EXPERIMENTAL-MODEL OF POSTNATAL JAUNDICE IN THE SUCKLING RAT - SUPPRESSION OF INDUCED HYPERBILIRUBINEMIA BY SN-PROTOPORPHYRIN [J].

DRUMMOND, GS ;

KAPPAS, A .

JOURNAL OF CLINICAL INVESTIGATION, 1984, 74 (01) :142-149

[6] MANGANESE AND ZINC BLOCKADE OF ENZYME-INDUCTION - STUDIES WITH MICROSOMAL HEME OXYGENASE [J].

DRUMMOND, GS ;

KAPPAS, A .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1979, 76 (10) :5331-5335

[7] SUPPRESSION OF HYPERBILIRUBINEMIA IN THE RAT NEONATE BY CHROMIUM-PROTOPORPHYRIN - INTERACTIONS OF METALLOPORPHYRINS WITH MICROSOMAL HEME OXYGENASE OF HUMAN SPLEEN [J].

DRUMMOND, GS ;

KAPPAS, A .

JOURNAL OF EXPERIMENTAL MEDICINE, 1982, 156 (06) :1878-1883

[8] SN-PROTOPORPHYRIN INHIBITION OF FETAL AND NEONATAL BRAIN HEME OXYGENASE - TRANS-PLACENTAL PASSAGE OF THE METALLOPORPHYRIN AND PRENATAL SUPPRESSION OF HYPERBILIRUBINEMIA IN THE NEWBORN ANIMAL [J].

DRUMMOND, GS ;

KAPPAS, A .

JOURNAL OF CLINICAL INVESTIGATION, 1986, 77 (03) :971-976

[9] REDUCTION OF THE C2 AND C-4 VINYL GROUPS OF SN-PROTOPORPHYRIN TO FORM SN-MESOPORPHYRIN MARKEDLY ENHANCES THE ABILITY OF THE METALLOPORPHYRIN TO INHIBIT INVIVO HEME CATABOLISM [J].

DRUMMOND, GS ;

GALBRAITH, RA ;

SARDANA, MK ;

KAPPAS, A .

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1987, 255 (01) :64-74

[10] COMPARATIVE PHOTOACTIVITY OF TIN AND ZINC PORPHYRIN INHIBITORS OF HEME OXYGENASE - PRONOUNCED PHOTOLABILITY OF THE ZINC-COMPOUNDS [J].

GREENBAUM, NL ;

KAPPAS, A .

PHOTOCHEMISTRY AND PHOTOBIOLOGY, 1991, 54 (02) :183-192