Ascorbic acid deficiency decreases hepatic cytochrome P-450, especially CYP2B1/2B2, and simultaneously induces heme oxygenase-1 gene expression in scurvy-prone ODS rats

• Published in: Bioscience, biotechnology, and biochemistry Vol. 78; no. 6; pp. 1060 - 1066
• Main Authors: Kobayashi, Misato, Hoshinaga, Yukiko, Miura, Natsuko, Tokuda, Yuki, Shigeoka, Shigeru, Murai, Atsushi, Horio, Fumihiko
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 03.06.2014; Oxford University Press
• Subjects: Animals; Aryl Hydrocarbon Hydroxylases - metabolism; ascorbic acid; CYP2B1/2B2; cytochrome P-450; Cytochrome P-450 CYP2B1 - metabolism; Disease Susceptibility; Electron Transport Complex IV - metabolism; Gene Expression Regulation, Enzymologic; heme oxygenase-1; Heme Oxygenase-1 - genetics; Lipopolysaccharides - pharmacology; Liver - drug effects; Liver - enzymology; Male; Microsomes, Liver - drug effects; Microsomes, Liver - enzymology; ODS rat; Phenobarbital - pharmacology; Rats; Scurvy - enzymology; Scurvy - genetics; Scurvy - metabolism; Steroid Hydroxylases - metabolism; ascorbic acid; cytochrome P-450; heme oxygenase-1; CYP2B1/2B2; ODS rat
• ISSN: 0916-8451; 1347-6947
• DOI: 10.1080/09168451.2014.910105

The mechanisms underlying the decrease in hepatic cytochrome P-450 (CYP) content in ascorbic acid deficiency was investigated in scurvy-prone ODS rats. First, male ODS rats were fed a diet containing sufficient ascorbic acid (control) or a diet without ascorbic acid (deficient) for 18 days, with or without the intraperitoneal injection of phenobarbital. Ascorbic acid deficiency decreased hepatic microsomal total CYP content, CYP2B1/2B2 protein, and mitochondrial cytochrome oxidase (COX) complex IV subunit I protein, and simultaneously increased heme oxygenase-1 protein in microsomes and mitochondria. Next, heme oxygenase-1 inducers, that is lipopolysaccharide and hemin, were administered to phenobaribital-treated ODS rats fed sufficient ascorbic acid. The administration of these inducers decreased hepatic microsomal total CYP content, CYP2B1/2B2 protein, and mitochondrial COX complex IV subunit I protein. These results suggested that the stimulation of hepatic heme oxygenase-1 expression by ascorbic acid deficiency caused the decrease in CYP content in liver. Ascorbic acid deficiency decreased hepatic microsomal total CYP content, CYP2B1/2B2 protein, and simultaneously increased heme oxygenase-1 protein.