Biotransformation of glucoaurantio-obtusin towards aurantio-obtusin increases the toxicity of irinotecan through increased inhibition towards SN-38 glucuronidation.
Phytother Res
; 28(10): 1577-80, 2014 Oct.
Article
en En
| MEDLINE
| ID: mdl-24842785
ABSTRACT
The present study aims to investigate the influence of irinotecan's toxicity by the biotransformation of glucoaurantio-obtusin to aurantio-obtusin. Intraperitoneal administration (i.p.) of 100 mg/kg aurantio-obtusin significantly increased the toxicity of irinotecan, but the i.p. administration of 100 mg/kg glucoaurantio-obtusin showed negligible influence towards irinotecan's toxicity. Furthermore, the mechanism was explained through determining the inhibition potential of glucoaurantio-obtusin and aurantio-obtusin towards the glucuronidation metabolism of SN-38 that has been regarded to be the major active product responsible for the toxicity of irinotecan. The results showed that aurantio-obtusin exhibited strong competitive inhibition towards the glucuronidation of SN-38, but negligible inhibition potential of glucoaurantio-obtusin towards SN-38 glucuronidation was observed. These results showed that biotransformation of glucoaurantio-obtusin towards aurantio-obtusin increased the toxicity of irinotecan through increased inhibition of SN-38 glucuronidation.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Camptotecina
/
Antraquinonas
/
Antineoplásicos Fitogénicos
Límite:
Animals
Idioma:
En
Revista:
Phytother Res
Asunto de la revista:
TERAPIAS COMPLEMENTARES
Año:
2014
Tipo del documento:
Article
País de afiliación:
China