Exploring cytochrome P450 under hypoxia: potential pharmacological
significance in drug metabolism and protection against high-altitude
diseases
Abstract
High-altitude hypoxia affects respiratory, central nervous,
cardiovascular, and endocrine systems. These outcomes affect the
expression of cytochrome P450 (CYP), the most important family of
metabolic enzymes in the body involved in the metabolism of both
exogenous and endogenous substances. Hypoxia influences CYP expression
and activity, mediating changes in drug and endogenous substance
metabolism, with endogenous substance metabolites playing a substantial
role in controlling high-altitude diseases. However, the mechanisms that
regulate CYP changes under hypoxic conditions and the effects of CYP
changes on drug and endogenous metabolism remain unclear. We examined
how CYP expression and function change during hypoxia and how they are
controlled by nuclear receptors, epigenetic modifications, cytokines,
and gut microbiota during hypoxia. This was done to understand how CYP
affects the metabolism of drugs and endogenous substances, such as
arachidonic acid, vitamins, and steroid hormones during hypoxia, and to
determine how CYP and its metabolites are involved in the
pathophysiology of diseases linked to high-altitude hypoxia.