Spaceflight Effects on Cytochrome P450 Content in Mouse Liver

<div><p>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.</p></div

Optimized mass spectrometric parameters of the peptides used for the quantitative analysis.

<p>* L—isotopically labeled leucine residue (Leu C₆¹³N₁¹⁵)</p><p>Optimized mass spectrometric parameters of the peptides used for the quantitative analysis.</p

MOESM1 of Plasma preparation to measure FDA-approved protein markers by selected reaction monitoring

Additional file 1: Figure S1. Extracted ion chromatograms of native and isotopically labelled proteotypic peptides (marked as “NAT” and “SIS”, respectively) obtained with Skyline software for the peptides of PlasmaDeepDive™ kit in Series #3: а SVLGQLGITK (Alpha 1-antitrypsin, P01009), 1592 fM; b GGYTLVSGYPK (Hemopexin, P02790), 475 fM; c GYTQQLAFR (Complement C3, P01024), 22 fM; d AVSPLPYLR (von Willebrand factor, P04275), 2 fM. Dashed lines indicate peak integration boundaries

MOESM4 of Plasma preparation to measure FDA-approved protein markers by selected reaction monitoring

Additional file 4: Figure S3. Comparison between protein concentration measured by SRM (Series #3) and by other approaches [14]

MOESM3 of Plasma preparation to measure FDA-approved protein markers by selected reaction monitoring

Additional file 3: Figure S2. Mean values of the coefficient of variation among technical runs in different series of measurement. Each point corresponds to the proteins detected in three technical runs (nine proteins in Series #1 and Series #3, and 11 proteins in Series #2)