PMID: 8964659Dec 1, 1995Paper

The role of nitric oxide generation in interferon-evoked cytochrome P450 down-regulation

International Journal of Immunopharmacology
P D Hodgson, K W Renton

Abstract

The down-regulation of cytochrome P450 during host defence involves one or more mediators of unknown source and identity. Owing to striking similarities in the features that are involved in the production of NO and the features involved in the down-regulation of cytochrome P450 we hypothesized that NO could be a mediator in the interferon-evoked loss of cytochrome P450. In these experiments the nitric oxide synthase inhibitor L-nitroarginine (5 mg/kg) failed to protect mice from the down-regulation of cytochrome P450, ethoxyresorufin dealkylase and para-nitrophenol hydroxylase in the liver following administration of the interferon inducer polyinosinic.polycytidylic acid. A higher dose of L-nitroarginine (30 mg/kg) given every 12 h for 3 days also did not protect against cytochrome P450 losses. In addition, no down-regulation of the enzyme was observed in animals treated with multiple doses of the NO-generating drugs glyceryl trinitrate (16 and 80 mg/kg given every 4 h for 16 h) and nitroprusside (20 and 100 mg/kg given every 4 h for 16 h). These results indicate that the down-regulation of cytochrome P450 by interferon or its inducers probably does not involve NO as a required intermediary.

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Citations

May 28, 2011·Journal of Physiology and Biochemistry·Thangaraj AnnaduraiPitchairaj Geraldine
Feb 10, 2000·Toxicology·K W Renton
Jun 8, 2010·BMC Bioinformatics·Assaf GottliebDavid Horn
Oct 4, 2016·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Tadatoshi TaninoEiichi Sakurai
Jan 9, 1998·Drug Metabolism Reviews·E T Morgan
Mar 21, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·C R GardnerD L Laskin
Oct 12, 1999·The American Journal of Physiology·C J KerkhofP Sipkema

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