Spaceflight Effects on Cytochrome P450 Content in Mouse Liver

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.

Fig 1. Extracted ion chromatogram of the target CYP peptides from the mouse liver digest obtained on LC-SRM-MS platform.

(A) Single SRM transition is shown for each target peptide. (B) Three SRM fragment ion pairs for SIS and natural peptide are shown for peptide GTTVITSLSSVLHDSK from CYP2C29 (retention time 22.9 min). The relative ion ratios are indicated in parentheses.