Zinc · protoporphyrin is a selective inhibitor of heme oxygenase activity in the neonatal rat

• Published in: Biochimica et biophysica acta Vol. 673; no. 3; pp. 339 - 350
• Main Author: Maines, Mahin D.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.01.1981
• Subjects: 5-Aminolevulinate Synthetase - metabolism; Animals; Animals, Newborn - metabolism; Cytochrome P-450; Heme Oxygenase (Decyclizing) - antagonists & inhibitors; Heme oxygenase inhibitor; Hene biosynthesis; Hydroxymethylbilane Synthase - metabolism; Hyperbilirubinemia; Kidney - enzymology; Kinetics; Liver - enzymology; Metalloporphyrin; Metalloporphyrins - pharmacology; Microsomes - enzymology; Mixed Function Oxygenases - antagonists & inhibitors; Neonatal rat; Porphyrins - pharmacology; Protoporphyrins - pharmacology; Rats; Spleen - enzymology; Metalloporphyrin; Hyperbilirubinemia; Heme oxygenase inhibitor; Neonatal rat; Cytochrome P-450; Hene biosynthesis
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/0304-4165(81)90465-7

The present study was undertaken to examine the liver, spleen and kidney heme oxygenase activity in the rat, and also to investigate the response of the enzyme to a variety of metalloporphyrin complexes. The enzyme activity in the liver and the kidney of 3–4-day-old rats was several-fold greater than the corresponding values in the adult animals; however, the splenic enzyme activity was markedly depressed in comparison to that of adult rats. During the first 2–3 weeks post-parturation period, the activity of heme oxygenase in the spleen progressively increased, and in 4 weeks approached the adult values. The treatment of the newborn animals with the metalloporphyrin complex, Zn · protoporphyrin-IX, inhibited heme oxygenase activity in the spleen, lier and the kidney. Sn · protoporphyrin treatment also inhibited the activity of the enzyme in the liver and the spleen. The mechanism of the inhibition appeared to be competitive in nature. In contrast, the treatment of the newborn animals with Co · protoporphyrin increased the activity of the enzyme in the tested organs. The treatment of newborn animals with Fe · protoporphyrin (heme) also increased heme oxygenase activity in the spleen and the kidney. In addition, Co · and Fe · protoporphyrin complexes inhibited the activity of δ-aminolevulinate synthetase in the spleen; Sn · protoporphyrin and Zn · protoporphyrin, however, did not alter the activity of this enzyme. The effects of Co · protoporphyrin and Zn · protoporphyrin on the microsomal contents of cytochromes P-450, b 5, the total heme, and the microsomal drug metabolism activity in the liver were compared. Zn · protoporphrin was ineffective in altering the indicated cellular variables. According to these findings Zn · protoporphyrin may be useful as an experimental tool for the selective suppression of heme degradation activity.