Duration of action and tissue distribution of zinc protoporphyrin in neonatal rats

P A Rodgers, D S Seidman, Po-Li Wei, P A Dennery, D K Stevenson

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Zinc protoporphyrin IX (ZnPP) has been shown to inhibit heme oxygenase (HO) activity effectively in vivo and has potential in the treatment of neonatal jaundice. Because this is a transitional or temporary condition lasting only several days, an effective chemopreventive agent with a relatively short duration of action would be desirable for the treatment of severe neonatal jaundice. To determine the effective duration of action of ZnPP, we administered either 40 nmol/g of body weight ZnPP or 5 microL/g body weight diluent intraperitoneally to neonatal rats 24-36 h after birth. Between 0 and 21 d after ZnPP dosing, the duration of action was investigated through measurements of serum bilirubin and hepatic and splenic HO inhibition, which were correlated to measurements of ZnPP distribution. Significant (p < 0.05) hepatic HO inhibition, ranging from 27 to 51%, was observed in the liver between 1 and 4 d after dosing, concurrent with a 23-28% reduction in serum bilirubin levels, and was associated with ZnPP tissue concentrations of 27-38 nmol/g. Splenic HO was not inhibited measurably by the much lower concentrations of ZnPP found in the spleen (2.8-20.1 nmol/g) between 0 and 21 d after dosing. Furthermore, HO isoform 1 (HO-1) induction was apparently not a confounding factor in the duration of action of ZnPP, because the modest increases in HO-1 protein levels were not sustained longer than 24 h after ZnPP administration. Our findings demonstrated that the duration of action of ZnPP in neonatal rats is less than 1 wk. The reduction in serum bilirubin levels, the short duration of action and minimal confounding effects suggest that ZnPP may be an effective chemopreventive agent for the treatment of severe neonatal jaundice.

Original languageEnglish
Pages (from-to)1041-9
Number of pages9
JournalPediatric Research
Volume39
Issue number6
DOIs
Publication statusPublished - Jun 1996
Externally publishedYes

Fingerprint

Tissue Distribution
Heme Oxygenase (Decyclizing)
Neonatal Jaundice
Bilirubin
Heme Oxygenase-1
Liver
zinc protoporphyrin
Serum
Body Weight
Protein Isoforms
Spleen
Parturition

Keywords

  • Animals
  • Animals, Newborn
  • Bilirubin
  • Body Weight
  • Gene Expression
  • Heme Oxygenase (Decyclizing)
  • Metalloporphyrins
  • Organ Size
  • Protoporphyrins
  • RNA, Messenger
  • Rats
  • Rats, Wistar
  • Tissue Distribution
  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

Cite this

Duration of action and tissue distribution of zinc protoporphyrin in neonatal rats. / Rodgers, P A; Seidman, D S; Wei, Po-Li; Dennery, P A; Stevenson, D K.

In: Pediatric Research, Vol. 39, No. 6, 06.1996, p. 1041-9.

Research output: Contribution to journalArticle

Rodgers, P A ; Seidman, D S ; Wei, Po-Li ; Dennery, P A ; Stevenson, D K. / Duration of action and tissue distribution of zinc protoporphyrin in neonatal rats. In: Pediatric Research. 1996 ; Vol. 39, No. 6. pp. 1041-9.
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T1 - Duration of action and tissue distribution of zinc protoporphyrin in neonatal rats

AU - Rodgers, P A

AU - Seidman, D S

AU - Wei, Po-Li

AU - Dennery, P A

AU - Stevenson, D K

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N2 - Zinc protoporphyrin IX (ZnPP) has been shown to inhibit heme oxygenase (HO) activity effectively in vivo and has potential in the treatment of neonatal jaundice. Because this is a transitional or temporary condition lasting only several days, an effective chemopreventive agent with a relatively short duration of action would be desirable for the treatment of severe neonatal jaundice. To determine the effective duration of action of ZnPP, we administered either 40 nmol/g of body weight ZnPP or 5 microL/g body weight diluent intraperitoneally to neonatal rats 24-36 h after birth. Between 0 and 21 d after ZnPP dosing, the duration of action was investigated through measurements of serum bilirubin and hepatic and splenic HO inhibition, which were correlated to measurements of ZnPP distribution. Significant (p < 0.05) hepatic HO inhibition, ranging from 27 to 51%, was observed in the liver between 1 and 4 d after dosing, concurrent with a 23-28% reduction in serum bilirubin levels, and was associated with ZnPP tissue concentrations of 27-38 nmol/g. Splenic HO was not inhibited measurably by the much lower concentrations of ZnPP found in the spleen (2.8-20.1 nmol/g) between 0 and 21 d after dosing. Furthermore, HO isoform 1 (HO-1) induction was apparently not a confounding factor in the duration of action of ZnPP, because the modest increases in HO-1 protein levels were not sustained longer than 24 h after ZnPP administration. Our findings demonstrated that the duration of action of ZnPP in neonatal rats is less than 1 wk. The reduction in serum bilirubin levels, the short duration of action and minimal confounding effects suggest that ZnPP may be an effective chemopreventive agent for the treatment of severe neonatal jaundice.

AB - Zinc protoporphyrin IX (ZnPP) has been shown to inhibit heme oxygenase (HO) activity effectively in vivo and has potential in the treatment of neonatal jaundice. Because this is a transitional or temporary condition lasting only several days, an effective chemopreventive agent with a relatively short duration of action would be desirable for the treatment of severe neonatal jaundice. To determine the effective duration of action of ZnPP, we administered either 40 nmol/g of body weight ZnPP or 5 microL/g body weight diluent intraperitoneally to neonatal rats 24-36 h after birth. Between 0 and 21 d after ZnPP dosing, the duration of action was investigated through measurements of serum bilirubin and hepatic and splenic HO inhibition, which were correlated to measurements of ZnPP distribution. Significant (p < 0.05) hepatic HO inhibition, ranging from 27 to 51%, was observed in the liver between 1 and 4 d after dosing, concurrent with a 23-28% reduction in serum bilirubin levels, and was associated with ZnPP tissue concentrations of 27-38 nmol/g. Splenic HO was not inhibited measurably by the much lower concentrations of ZnPP found in the spleen (2.8-20.1 nmol/g) between 0 and 21 d after dosing. Furthermore, HO isoform 1 (HO-1) induction was apparently not a confounding factor in the duration of action of ZnPP, because the modest increases in HO-1 protein levels were not sustained longer than 24 h after ZnPP administration. Our findings demonstrated that the duration of action of ZnPP in neonatal rats is less than 1 wk. The reduction in serum bilirubin levels, the short duration of action and minimal confounding effects suggest that ZnPP may be an effective chemopreventive agent for the treatment of severe neonatal jaundice.

KW - Animals

KW - Animals, Newborn

KW - Bilirubin

KW - Body Weight

KW - Gene Expression

KW - Heme Oxygenase (Decyclizing)

KW - Metalloporphyrins

KW - Organ Size

KW - Protoporphyrins

KW - RNA, Messenger

KW - Rats

KW - Rats, Wistar

KW - Tissue Distribution

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

KW - Research Support, U.S. Gov't, P.H.S.

U2 - 10.1203/00006450-199606000-00018

DO - 10.1203/00006450-199606000-00018

M3 - Article

C2 - 8725267

VL - 39

SP - 1041

EP - 1049

JO - Pediatric Research

JF - Pediatric Research

SN - 0031-3998

IS - 6

ER -