Studies on hepatotoxicity and toxicokinetics of colchicine.
colchicine
hepatotoxicity
metabolism
toxicokinetics
Journal
Journal of biochemical and molecular toxicology
ISSN: 1099-0461
Titre abrégé: J Biochem Mol Toxicol
Pays: United States
ID NLM: 9717231
Informations de publication
Date de publication:
Sep 2019
Sep 2019
Historique:
received:
17
09
2018
revised:
29
04
2019
accepted:
02
07
2019
pubmed:
25
7
2019
medline:
18
12
2019
entrez:
24
7
2019
Statut:
ppublish
Résumé
Colchicine (COL) is an alkaloid existing in plants of Liliaceous colchicum. It has widely been used in the treatments of many diseases, such as gout, Familial Mediterranean Fever, and tumor. However, the adverse effects of COL are an obstacle to its safe use. The present studies explored the role of metabolic demethylation in the development of COL-induced hepatotoxicity. We found that inhibition of CYP3A increased the susceptibility of mice to COL hepatotoxicity, and induction of CYP3A decreased the susceptibility of animals to the hepatotoxicity. The toxicokinetic study demonstrated that pretreatment with ketoconazole caused elevated area under the concentration-time curve of COL. Three demethylation metabolites of COL were found to be less hepatotoxic than the parent compound. It appears that the formation of electrophilic demethylation metabolites was not involved in the development of COL-induced liver injury.
Substances chimiques
Cytochrome P-450 CYP3A
EC 1.14.14.1
Ketoconazole
R9400W927I
Colchicine
SML2Y3J35T
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e22366Subventions
Organisme : National Natural Science Foundation of China
ID : 81830104
Organisme : National Natural Science Foundation of China
ID : 81773813
Organisme : National Natural Science Foundation of China
ID : 81430086
Informations de copyright
© 2019 Wiley Periodicals, Inc.