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.
Highlights
Along with the growing knowledge about spaceflights it becomes obvious their influence on living organisms, including the human being
The enzymes of cytochrome P450 superfamily, which are an important part of the liver monooxygenase system, play a key role in the Phase I drug metabolism
Activity of the monooxygenase system towards a particular drug is mainly determined by concentrations of cytochrome P450 isoforms specific to it [1]
Summary
Along with the growing knowledge about spaceflights it becomes obvious their influence on living organisms, including the human being. The "Bion" project of the Institute of Biomedical Problems of the Russian Academy of Sciences (IBMP RAS) includes a series of space orbital flights of animals on biosatellites and is aimed at identifying the cellular and molecular mechanisms of adaptation to microgravity. The information obtained can be used to ensure astronauts’ workability in long-term space flights, correcting both the diet and possible medical treatment. The efficiency of the medication is known to be determined by the activity of the drug metabolism system. The enzymes of cytochrome P450 superfamily, which are an important part of the liver monooxygenase system, play a key role in the Phase I drug metabolism. Activity of the monooxygenase system towards a particular drug is mainly determined by concentrations of cytochrome P450 isoforms specific to it [1]
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