scholarly journals Sn-protoporphyrin blocks the increase in serum bilirubin levels that develops postnatally in homozygous Gunn rats.

1988 ◽  
Vol 167 (3) ◽  
pp. 1247-1252 ◽  
Author(s):  
T R Sisson ◽  
G S Drummond ◽  
D Samonte ◽  
R Calabio ◽  
A Kappas
Keyword(s):  
Serum Bilirubin ◽  
Postnatal Period ◽  
Transferase Activity ◽  
Bilirubin Concentration ◽  
Heme Oxygenase Activity ◽  
Gunn Rats ◽  
Oxygenase Activity ◽  
Low Levels ◽  
Genetically Determined ◽  
Hepatic Cytochrome

Administration of Sn-protoporphyrin to Gunn rats that are characterized by a genetically determined absence of UDP-glucuronyl transferase activity for bilirubin, 24-30 h after birth, prevented the marked increase in serum bilirubin concentration that occurs in these animals in the postnatal period. A second administration of Sn-protoporphyrin at day 6 maintained serum bilirubin levels in the neonates at the initial level for an additional 6 d. In contrast, in untreated Gunn neonates, serum bilirubin levels increased substantially as expected during the immediate 2-wk period after birth. Studies in adult Gunn rats demonstrated that Sn-protoporphyrin administration diminished biliary bilirubin output, decreased tissue heme oxygenase activity, and did not alter hepatic cytochrome P450 levels. These findings raise the possibility that Sn-protoporphyrin may prove clinically useful in maintaining low levels of serum bilirubin in congenitally jaundiced individuals, such as patients with the Crigler-Najjar syndrome.

Tin-protoporphyrin in the Management of Children With Crigler-Najjar Disease

PEDIATRICS ◽  
1990 ◽  
Vol 86 (1) ◽  
pp. 152-152
Author(s):  
FIRMINO F. RUBALTELLI ◽  
GIULIO JORI
Keyword(s):  
Serum Bilirubin ◽  
Bilirubin Concentration ◽  
Tin Protoporphyrin ◽  
Low Levels ◽  
Serum Bilirubin Concentration

In Reply.— We have considered carefully the points raised by Dr McDonagh and answer as follows: Regarding points 1 and 2, Fig 2 (second plot from the bottom) of our paper clearly shows that administration of SnPp to the patient with Crigler-Najjar type 1 disease reduces the serum bilirubin concentration to values ranging between 12 and 15 mg/dL for at least a week. In the absence of SnPp treatment, the infant never reached such low levels even during sunny seasons, unless phototherapy was performed.

scholarly journals Prevention of neonatal hyperbilirubinaemia in non-human primates by Zn-protoporphyrin

1985 ◽  
Vol 226 (1) ◽  
pp. 51-57 ◽  
Author(s):  
M K Qato ◽  
M D Maines
Keyword(s):  
Urinary Excretion ◽  
Serum Bilirubin ◽  
Postnatal Period ◽  
Biliverdin Reductase ◽  
Oxygenase Activity ◽  
Haem Oxygenase ◽  
Clinical Conditions ◽  
Cytochrome P 450 ◽  
The Brain ◽  
Dependent Processes

Non-human primates were used as a model of human neonatal hyperbilirubinaemia and its chemotherapeutic suppression. High levels of haem oxygenase activity were detected in the liver and the spleen of neonatal rhesus (Macaca mulatta) and cynomolgus (Macaca irus) monkeys. When 1-day-old neonatal animals were given a single injection of Zn-protoporphyrin (40 mumol/kg, subcutaneously), serum bilirubin levels declined to nearly normal adult levels within 24 h and remained suppressed throughout the postnatal period (12 days). This treatment inhibited the activities of haem oxygenase and biliverdin reductase in the liver and the spleen, without affecting that of the brain. Zn-protoporphyrin treatment did not alter the activity of brain biliverdin reductase or increase brain bilirubin levels. The biological disposition of Zn-protoporphyrin was examined by measuring the biliary and urinary excretion of the metalloporphyrin complex, as well as its uptake and deposition in blood cells and tissues. Biliary excretion of the metalloporphyrin was minimal (0.12% over a 28 h period), and no evidence was detected for the urinary excretion of Zn-protoporphyrin. However, the concentration of metalloporphyrin in erythrocytes increased over the duration of the experiment (11 days) to such an extent that 46% of the administered compound was taken up by the cells. It appeared that the molecular basis for the sustained suppression of haem oxygenase activity and bilirubin production by Zn-protoporphyrin involved the release of the metalloporphyrin in the normal process of the degradation of fetal erythrocytes. The scope of the biological activity of Zn-protoporphyrin to alter haem-dependent processes appeared limited in nature, insofar as the microsomal contents of cytochrome P-450 and b5, as well as the aniline hydroxylase, were similar to those of the control animals. Also, the concentration of glutathione in the liver was unchanged. These findings suggest the potential usefulness of Zn-protoporphyrin in experimental and perhaps clinical conditions in which hyperbilirubinaemia occurs.

scholarly journals Study of the developmental pattern of heme catabolism in liver and the effects of cobalt on cytochrome P-450 and the rate of heme oxidation during the neonatal period.

1975 ◽  
Vol 141 (6) ◽  
pp. 1400-1410 ◽  
Author(s):  
M D Maines ◽  
A Kappas
Keyword(s):  
Enzyme Activity ◽  
Heme Oxygenase ◽  
Developmental Stages ◽  
Postnatal Period ◽  
Normal Adult ◽  
Heme Oxygenase Activity ◽  
Oxygenase Activity ◽  
Nursing Mothers ◽  
Drug Oxidation ◽  
Cytochrome P 450

The comparative development patterns of heme oxidation andof cytochrome P-450 dependent drug oxidation in rat liver were examined. High levels of heme oxygenase activity were present in whole embryo preparations at day 13 of gestation. At birth this enzyme activity in liver was approximately equal to that of normal adult liver. In the immediate postnatal period the rate of hepatic heme oxidation increased sharply, reaching levels 3-5 times normal during the first week postpartum. Thereafter, this enzyme activity progressively decreased and returned to normal adult levels by the 28th postpartum day. The development of microsomal heme oxidation and of P-450 dependent drug oxidation exhibited reciprocal patterns, with the latter being at low levels of activity during the immediate postnatal period and reaching adult activity only 4 or more wk after birth. Cobalt injected into pregnant animals or in to nursing mothers did not induce heme oxygenase in the fetus or suckling neonate. However, when treated directly with the metal, 4-day old neonates exhibited a small induction response of this enzyme; and the inducibility of heme oxygenase increased gradually to fully adult levels by the end of the 4th postpartum week. Cobalt at all postnatal developmental stages was capable of diminishing hepatic contents of total microsomal heme and P-450; however this effect of the metal was small in the immediate period after birth and increased progressively with maturation. These findings demonstrate that the patterns of development of hepatic capacity for carrying out the oxidation of heme and the P-450 dependent oxidation of drugs are different and thus provide further evidence that these microsomal enzyme systems are distinct from each other and under separate regulatory mechanisms. The degree of induction response for hepatic heme oxygenase evoked by the trace metal, cobalt, was also shown to have developmental determinants as did the susceptibility of hepatic cytochrome P-450 to degradation by this metal. The very high levels of hepatic heme oxygenase activity which characterize neonates during the first week of life indicate that over-production of bilirubin contributes significantly to the mechanism of neonatal jaundice.

scholarly journals Suppression of hyperbilirubinemia in the rat neonate by chromium-protoporphyrin. Interactions of metalloporphyrins with microsomal heme oxygenase of human spleen.

1982 ◽  
Vol 156 (6) ◽  
pp. 1878-1883 ◽  
Author(s):  
G S Drummond ◽  
A Kappas
Keyword(s):  
Single Dose ◽  
Heme Oxygenase ◽  
Competitive Inhibitor ◽  
Bile Pigment ◽  
Human Spleen ◽  
Oxidation Activity ◽  
Heme Oxygenase Activity ◽  
Heme Degradation ◽  
Oxygenase Activity ◽  
Liver And Kidney

The synthetic metalloporphyrin, Cr-protoporphyrin, as a potent competitive inhibitor of heme oxygenase activity in rat spleen, liver, and kidney. When administered to neonatal animals in a single dose immediately after birth, Cr-protoporphyrin suppresses postnatal hyperbilirubinemia and produces a marked and sustained lowering of heme oxidation activity in liver, spleen, and kidney. The metalloporphyrin also potently inhibited the rate of heme degradation to bile pigment in human spleen.

Heme oxygenase activity causes transient hypersensitivity to oxidative ultraviolet a radiation that depends on release of iron from heme

2000 ◽  
Vol 28 (8) ◽  
pp. 1191-1196 ◽  
Author(s):  
Egil Kvam ◽  
Vidya Hejmadi ◽  
Stefan Ryter ◽  
Charareh Pourzand ◽  
Rex M Tyrrell
Keyword(s):  
Heme Oxygenase ◽  
Ultraviolet A ◽  
Heme Oxygenase Activity ◽  
Oxygenase Activity
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