Systemic effects of orally-administered zinc and tin (IV) metalloporphyrins on heme oxygenase expression in mice

被引:26
作者
Morioka, I
Wong, RJ
Abate, A
Vreman, HJ
Contag, CH
Stevenson, DK
机构
[1] Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA
[2] Kobe Univ, Grad Sch Med, Dept Pediat, Kobe, Hyogo 6500017, Japan
关键词
D O I
10.1203/01.pdr.0000215088.71481.a6
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
Some metalloporphyrins (Mps) inhibit heme oxygenase (HO), the rate-limiting enzyme in the production of bilirubin, and are potential compounds for the treatment of neonatal jaundice. We studied the safety and efficacy of Mps following oral administration. Adult HO-1-luc reporter mice were administered 30 mu mol/kg body weight of tin mesoporphyrin (SnMP), zinc his glycol deuteroporphyrin (ZnBG), or zinc protoporphyrin (ZnPP), or vehicle by oral gavage. Bilirubin production was measured as total body carbon monoxide (CO) excretion (VeCO). HO activity was quantitated via CO measurements by gas chromatography. HO-1 protein was determined by Western blot. HO-I transcription levels were assessed by in vivo bioluminescence imaging. A significant 28% decrease in bilirubin production occurred within 3h of SnMP treatment and persisted beyond 48h. Bilirubin production decreased 15% and 9% by 3h after administration of ZnBG and ZnPP, respectively, but returned to baseline within 48h. Maximal inhibition of liver, spleen, and intestine HO activity was seen at 3h with inhibitory effects decreasing in the order: SnMP >= ZnBG >= ZnPP. After SnMP treatment, HO-1 transcription increased 5.7-fold after 24h. Furthermore, liver and spleen HO-1 protein significantly increased 3.7- and 2.0-fold, respectively, after 24h. HO-1 transcription and protein were not affected in ZnBG- or ZnPP-treated mice. We conclude that the three Mps are absorbed at different rates in the Mouse and affect bilirubin production and HO-1 expression in a tissue- and time-dependent manner.
引用
收藏
页码:667 / 672
页数:6
相关论文
共 36 条
[1]  
Appleton SD, 1999, DRUG METAB DISPOS, V27, P1214
[2]   ABSORPTION OF BETA-ADRENERGIC-BLOCKING AGENT, NADOLOL, BY MICE, RATS, HAMSTERS, RABBITS, DOGS, MONKEYS, AND MAN - UNUSUAL SPECIES-DIFFERENCE [J].
DREYFUSS, J ;
SHAW, JM ;
ROSS, JJ .
XENOBIOTICA, 1978, 8 (08) :503-508
[3]  
DRUMMOND GS, 1992, GASTROENTEROLOGY, V102, P1170
[4]   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
[5]   Singlet oxygen generation by photodynamic agents [J].
Fernandez, JM ;
Bilgin, MD ;
Grossweiner, LI .
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY, 1997, 37 (1-2) :131-140
[6]   Effects of Metalloporphyrins on Heme Oxygenase-1 Transcription: Correlative Cell Culture Assays Guide In Vivo Imaging [J].
Hajdena-Dawson, Monica ;
Zhang, Weisheng ;
Contag, Pamela R. ;
Wong, Ronald J. ;
Vreman, Hendrik J. ;
Stevenson, David K. ;
Contag, Christopher H. .
Molecular Imaging, 2003, 2 (03) :138-149
[7]   MORTALITY OF METALLOPORPHYRIN-TREATED NEONATAL RATS AFTER LIGHT EXPOSURE [J].
HINTZ, SR ;
VREMAN, HJ ;
STEVENSON, DK .
DEVELOPMENTAL PHARMACOLOGY AND THERAPEUTICS, 1990, 14 (03) :187-192
[8]   A single dose of Sn-mesoporphyrin prevents development of severe hyperbilirubinemia in glucose-6-phosphate dehydrogenase-deficient newborns [J].
Kappas, A ;
Drummond, GS ;
Valaes, T .
PEDIATRICS, 2001, 108 (01) :25-30
[9]   DANGEROUS EFFECTS OF TIN-PROTOPORPHYRIN PLUS PHOTOIRRADIATION ON NEONATAL RATS [J].
KEINO, H ;
NAGAE, H ;
MIMURA, S ;
WATANABE, K ;
KASHIWAMATA, S .
EUROPEAN JOURNAL OF PEDIATRICS, 1990, 149 (04) :278-279
[10]   The heme oxygenase system: A regulator of second messenger gases [J].
Maines, MD .
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, 1997, 37 :517-554