Affiliation:
1. Research Center for High Altitude Medicine, Qinghai University, Xining, China
2. Medical College, Qinghai University, Xining, China
3. State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, Xining, China
Abstract
Background:
Hypoxia has a negative effect on the cardiovascular system, nervous system, and metabolism,
which contributes to potential changes in drug absorption, distribution, metabolism, and excretion (ADME).
However, hypoxia can also alter the expression of microRNA (miRNA), thereby regulating drug-metabolizing enzymes,
transporters, and ADME genes, such as hypoxia-inducible factor, inflammatory cytokine, nuclear receptor,
etc. Therefore, it is crucial to study the role of miRNA in the regulation of drug-metabolizing enzymes and transporters
under hypoxia.
Methods:
A systematic review of published studies was carried out to investigate the role of miRNA in the regulation
of drug-metabolizing enzymes and transporters under hypoxia. Data and information on expression changes in
miRNA, drug-metabolizing enzymes, and transporters under hypoxia were analyzed and summarized.
Results:
Hypoxia can up or down-regulate the expression of miRNA. The effect of hypoxia on Cytochrome P450
(CYP450) is still a subject of debate. The widespread belief is that hypoxia decreased the activity and expression of
CYP1A1, CYP1A2, CYP2E1, and CYP3A1 and increased those of CYP3A6 and CYP2D1 in rats. Hypoxia increased
the expression of a multidrug resistance-associated protein, breast cancer resistance protein, peptide transporter,
organic cation transporter, and organic anion transporter. miRNA negatively regulated the expression of drugmetabolizing
enzymes and transporters.
Conclusion:
The findings of this review indicated that miRNA plays a key role in the expression changes of drugmetabolizing
enzymes and transporters under hypoxia.
Funder
Key Research Foundation of Development and Transformation of Qinghai Province
Qinghai Innovation Platform Construction Project
National Natural Science Foundation of China
Publisher
Bentham Science Publishers Ltd.
Subject
Clinical Biochemistry,Pharmacology
Cited by
10 articles.
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