Spaceflight Effects on Cytochrome P450 Content in Mouse Liver

PLoS One. 2015 Nov 11;10(11):e0142374. doi: 10.1371/journal.pone.0142374. eCollection 2015.

Abstract

Hard conditions of long-term manned spaceflight can affect functions of many biological systems including a system of drug metabolism. The cytochrome P450 (CYP) superfamily plays a key role in the drug metabolism. In this study we examined the hepatic content of some P450 isoforms in mice exposed to 30 days of space flight and microgravity. The CYP content was established by the mass-spectrometric method of selected reaction monitoring (SRM). Significant changes in the CYP2C29, CYP2E1 and CYP1A2 contents were detected in mice of the flight group compared to the ground control group. Within seven days after landing and corresponding recovery period changes in the content of CYP2C29 and CYP1A2 returned to the control level, while the CYP2E1 level remained elevated. The induction of enzyme observed in the mice in the conditions of the spaceflight could lead to an accelerated biotransformation and change in efficiency of pharmacological agents, metabolizing by corresponding CYP isoforms. Such possibility of an individual pharmacological response to medication during long-term spaceflights and early period of postflight adaptation should be taken into account in space medicine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytochrome P-450 CYP1A2 / metabolism*
  • Cytochrome P-450 CYP2E1 / metabolism*
  • Cytochrome P-450 Enzyme System / metabolism*
  • Cytochrome P450 Family 2
  • Liver / enzymology*
  • Mice
  • Microsomes, Liver / metabolism
  • Space Flight*

Substances

  • Cytochrome P-450 Enzyme System
  • Cytochrome P-450 CYP2E1
  • Cyp2c29 protein, mouse
  • Cytochrome P-450 CYP1A2
  • Cytochrome P450 Family 2

Grants and funding

This work was supported by the Russian Science Foundation, RSF grant № 14-25-00132, (http://www.rscf.ru/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.