Altered gene expression of hepatic cytochrome P450 in a rat model of intermittent hypoxia with emphysema.

Patients with respiratory overlap syndrome (OS), defined as concomitant chronic obstructive pulmonary disease and obstructive sleep apnea syndrome, may exhibit an increased blood concentration of ingested drugs. This poor elimination of drugs is primarily attributed to downregulated gene expression of the drug‑metabolizing cytochrome P450 enzymes (CYPs) in the liver. However, the underlying mechanisms of the decreased expression of CYPs in OS are poorly understood. In order to address this, a rat model of intermittent hypoxia with emphysema was evaluated in the present study, by analyzing liver gene expression using the reverse transcription‑quantitative polymerase chain reaction. Intermittent hypoxia and cigarette smoke exposure caused upregulation of hepatic inflammatory cytokines, while CYPs were downregulated. This downregulation of CYPs was associated with an increase in nuclear factor (NF)‑κB expression and a decrease in the expression of nuclear receptors pregnane X receptor, constitutive androstane receptor and glucocorticoid receptor, which are the upstream regulatory molecules of CYPs. The results of the present study indicated that, during the development of OS, systematic inflammatory reactions may downregulate hepatic CYP gene expression via the NF‑κB signaling pathway.