Cargando…

The Accumulation of Psoralen Contributes to Its Hepatotoxicity Revealed by Pharmacokinetic and Toxicokinetic Study after Repeated Administration

[Image: see text] Psoralen is a furanocoumarin compound found in many herb medicines and is claimed to contribute to the hepatotoxicity caused by lots of traditional Chinese medicine. So far, there has been no research on the differences in pharmacokinetics of single and repeated dosing of psoralen....

Descripción completa

Detalles Bibliográficos
Autores principales: Yang, Li, Yu, Ying-li, Cheng, Li-yuan, Zhang, Pan-yang, Zhang, Yue, Zhou, Kun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2020
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144168/
https://www.ncbi.nlm.nih.gov/pubmed/32280872
http://dx.doi.org/10.1021/acsomega.9b04153
Descripción
Sumario:[Image: see text] Psoralen is a furanocoumarin compound found in many herb medicines and is claimed to contribute to the hepatotoxicity caused by lots of traditional Chinese medicine. So far, there has been no research on the differences in pharmacokinetics of single and repeated dosing of psoralen. Moreover, the research on the cumulative toxicity of low concentration and long-term administration on cells has not been reported. Therefore, this study investigated the pharmacokinetic differences and the accumulated cytotoxicity of psoralen from repeated administration. The study found that after single or repeated administration of psoralen for 3 months at various dosages (14, 28, and 56 mg/kg), the pharmacokinetic parameters of female rats between single dose and repeated dose administration are totally different. Compared with a single administration, multiple administrations increased psoralen’s in vivo exposure, prolonged the peak time, prolonged the half-life of the drug, reduced the drug clearance rate, and prolonged the drug’s stay in the body. HepG2 cells were exposed to low doses (5, 10, 20, or 40 μM) of psoralen for 1, 2, 3, or 4 days. A 20 and 40 μM dose of psoralen did not induced cell death in the 1st day but significantly decreased the cell viability at the 3rd and 4th day of repeated administration, respectively. In addition, multiple administrations of psoralen decreased cell viability due to G2 arrest.