Pregnenolone 16α-carbonitrile negatively regulates hippocampal cytochrome P450 enzymes and ameliorates phenytoin-induced hippocampal neurotoxicity.

ABSTRACT: The central nervous system is susceptible to the modulation of various neurophysiological processes by the cytochrome P450 enzyme (CYP), which plays a crucial role in the metabolism of neurosteroids. The antiepileptic drug phenytoin (PHT) has been observed to induce neuronal side effects in patients, which could be attributed to its induction of CYP expression and testosterone (TES) metabolism in the hippocampus. While pregnane X receptor (PXR) is widely known for its regulatory function of CYPs in the liver, we have discovered that the treatment of mice with pregnenolone 16α-carbonitrile (PCN), a PXR agonist, has differential effects on CYP expression in the liver and hippocampus. Specifically, the PCN treatment resulted in the induction of cytochrome P450, family 3, subfamily a, polypept

SUBMITTER: Zhang S 

PROVIDER: S-EPMC10785155 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature