ArticlePharmacological reports : PR2023
The effect of brain serotonin deficit (TPH2-KO) on the expression and activity of liver cytochrome P450 enzymes in aging male Dark Agouti rats.
Article in Pharmacological reports : PR, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 4 citations in OpenAlex.
- Role of central and peripheral serotonin in liver physiology and diseases.Theranostics · 2026Review
- CYP8B1 is a prognostic biomarker with important functional implications in hepatocellular carcinoma.Oncology reports · 2025Article
- The neuroendocrine regulation of hepatic cytochrome P450 by N-methyl-D-aspartate receptors in the paraventricular and arcuate nuclei of the hypothalamus.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Cannabinoids and the endocannabinoid system in the regulation of cytochrome P450 metabolic activity-a review.Frontiers in pharmacology · 2025Review
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundLiver cytochrome P450 (CYP) greatly contributes to the metabolism of endogenous substances and drugs. Recent studies have demonstrated that CYP expression in the liver is controlled by the central nervous system via hormonal pathways. In particular, the expression of hepatic CYPs is negatively regulated by the brain serotoninergic system. The present study aimed to investigate changes in the function of the main liver drug-metabolizing CYP enzymes as a result of serotonin depletion in the brain of aging rats, caused by knockout of brain tryptophan hydroxylase gene (TPH2-KO).
methodsThe hepatic CYP mRNA (qRT-PCR), protein level (Western blotting) and activity (HPLC), and serum hormone levels (ELISA) were measured in Dark Agouti wild-type (WT) male rats (mature 3.5-month-old and senescent 21-month-old) and in TPH2-KO senescent animals.
resultsThe expression/activity of the studied CYPs decreased with age in the liver of wild-type rats. The deprivation of serotonin in the brain of aging males decreased the mRNA level of most of the studied CYPs (CYP1A/2A/2B/3A), and lowered the protein level of CYP2C11 and CYP3A. In contrast, the activities of CYP2C11, CYP3A and CYP2C6 were increased. The expression of cytochrome b
conclusionsRat liver cytochrome P450 functions deteriorate with age, which may impair drug metabolism. The TPH2 knockout, which deprives brain serotonin, affects cytochrome P450 expression and activity differently in mature and senescent male rats.
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