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Biotransformation of Glucoaurantio‐Obtusin Towards Aurantio‐Obtusin Increases the Toxicity of Irinotecan Through Increased Inhibition Towards SN‐38 Glucuronidation
Author(s) -
Yu Jian,
Han JingChun,
Gao YaJie
Publication year - 2014
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.5162
Subject(s) - glucuronidation , toxicity , chemistry , biotransformation , irinotecan , pharmacology , sn 38 , medicine , biochemistry , enzyme , organic chemistry , microsome , cancer , colorectal cancer
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. Copyright © 2014 John Wiley & Sons, Ltd.