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Toxicokinetics and tissue distribution of phalloidin in mice.
- Source :
-
Food & Chemical Toxicology . Sep2023, Vol. 179, pN.PAG-N.PAG. 1p. - Publication Year :
- 2023
-
Abstract
- Phalloidin, a bicyclic heptapeptide found in Amanita mushroom, specifically binds to F-actin in the liver causing cholestatic hepatotoxicity. However, the toxicokinetics and tissue distribution properties of phalloidin as well as their underlying mechanisms have to be studied further. The area under the plasma concentration curve (AUC) of phalloidin increased in proportion to the doses (0.2, 0.4, and 0.8 mg/kg for intravenous injection and 2, 5, and 10 mg/kg for oral administration). Phalloidin exhibited dose-independent low volume of distribution (395.6–456.9 mL/kg) and clearance (21.4–25.5 mL/min/kg) and low oral bioavailability (2.4%–3.3%). This could be supported with its low absorptive permeability (0.23 ± 0.05 × 10−6 cm/s) in Caco-2 cells. The tissue-to-plasma AUC ratios of intravenously injected and orally administered phalloidin were the highest in the liver and intestines, respectively, and also high in the kidneys, suggesting that the liver, kidneys, and intestines could be susceptible to phalloidin exposure and that active transport via the hepatic and renal organic anion transporters (OATP1B1, OATP1B3, and OAT3) may contribute to the higher distribution of phalloidin in the liver and kidneys. • LC-HRMS method was validated for quantification of phalloidin in mouse plasma. • Toxicokinetics and tissue distribution of phalloidin were characterized in mice. • Phalloidin is a substrate for OAT3, OATP1B1, and OATP1B3. • Phalloidin showed no inhibitory effects on human major CYP, UGT, and transporters. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 02786915
- Volume :
- 179
- Database :
- Academic Search Index
- Journal :
- Food & Chemical Toxicology
- Publication Type :
- Academic Journal
- Accession number :
- 171341993
- Full Text :
- https://doi.org/10.1016/j.fct.2023.113994