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Eksperimental'naia i klinicheskaia farmakologiia

[Effect of hypoxic stress on xenobiotic metabolism and activities of various isoforms of cytochrome P-450].


PMID 11589108

Abstract

It was shown that animals divided into groups with respect to the initial sensitivity (low and high resistance) to hypoxia (lack of oxygen in air) differ by their liver monooxygenase enzyme complex reaction to the model acute hypoxia. Low-resistant rats exhibited an increase in cytochromes P-450 and b5, in the rate of oxidative metabolism of amidopyrine, aniline, and ethoxyresorufine, and in the rate of antipyrine elimination (manifested by a decrease in the elimination half time and by an increase in the elimination constant), which is evidence of the increasing activity of cytochromes P-450, 1A1, 1A2, 2C8, and 3A1. In response to acute hypoxia, highly hypoxia-resistant animals exhibited an increase in the rates of diazepam and methoxyresorufine metabolism, which reflected a higher catalytic activity of P-450, 2C6, 2B1, and 1A2 isoforms. At the same time, the rate of antipyrine elimination decreases (the elimination half-time increases, while the clearance and the elimination constant decrease).

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