Effects of tin-porphyrins on developmental changes in hepatic cytochrome P450 content, selected P450-dependent drug-metabolizing enzyme activities and brain glutathione levels in the newborn rat.
Sn-mesoporphyrin is considerably more effective than Sn-protoporphyrin in inhibiting bilirubin production in vivo, in the experimental animal. In this study the effects of Sn-mesoporphyrin, administered in doses ranging from 1 to 20 mumol/kg b.w., on the developmental patterns of hepatic cytochrome P450 content and cytochrome P450-dependent drug metabolism in rat neonates were examined at various time points during the 5-week period immediately after birth. No detrimental alterations in cytochrome P450 content or in cytochrome P450-dependent drug metabolism were observed. In addition no deleterious effects were noted on total glutathione content in brain of Sn-mesoporphyrin-treated animals. After single doses of Sn-protoporphyrin of 20, 50 or 100 mumol/kg b.w. were administered at birth, transient decreases in hepatic cytochrome P450 content (days 1 and 2), and ethylmorphine demethylase (days 2 and 5) and 7-ethoxycoumarin deethylase (days 1, 2 and 5) activities were observed in the period immediately after birth. However no sustained alterations in the developmental patterns of these enzymes were observed even at the highest dose (100 mumol/kg b.w.) of Sn-protoporphyrin administered. These findings indicate that in the doses utilized in this study both metalloporphyrins have no long-term effects on cytochrome P450-dependent drug metabolism. Furthermore, in doses up to 20 mumol/kg b.w., neither compound produced any short-term effects on hepatic cytochrome P450 content or functional activity in newborn rats.
Drummond
G S
GS
Rockefeller University Hospital, New York, N.Y.
Rosenberg
D W
DW
Kihlström-Johanson
A C
AC
Kappas
A
A
D000624:5-Aminolevulinate Synthetase / Q000378:metabolism; D015660:7-Alkoxycoumarin O-Dealkylase / Q000378:metabolism; D000815:Aniline Hydroxylase / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001921:Brain / Q000254:growth & development; D001923:Brain Chemistry / Q000187:drug effects*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005037:Ethylmorphine-N-Demethylase / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development; D008665:Metalloporphyrins / Q000494:pharmacology*; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011166:Porphyrins / Q000494:pharmacology*; D011247:Pregnancy; D011524:Protoporphyrins / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D008665:Metalloporphyrins; D011166:Porphyrins; D011524:Protoporphyrins; C055421:tin mesoporphyrin; D003577:Cytochrome P-450 Enzyme System; C032628:tin protoporphyrin IX; D006899:Mixed Function Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase; D000815:Aniline Hydroxylase; D006419:Heme Oxygenase (Decyclizing); D005037:Ethylmorphine-N-Demethylase; D000624:5-Aminolevulinate Synthetase; D005978:Glutathione