Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/30764
Title: Disposition and metabolism of the cancer chemopreventive agent curcumin in rodents and humans
Authors: Ireson, Christopher Richard.
Award date: 2002
Presented at: University of Leicester
Abstract: Curcumin, the major yellow pigment in the herb turmeric, has been shown to possess cancer chemopreventive activity in rodents. The bioavailability of curcumin in rodents is thought to be poor, but concentrations of 10-5-10-4 M curcumin are required for biological activity. The role of curcumin metabolites in the biological efficacy of curcumin is not clear. In order to improve our understanding of pharmacokinetic issues which may impinge on the pharmacology of curcumin, its disposition and metabolism was studied in three different settings: i) in subcellular fractions of intestine and liver from rodents and humans, ii) in intact hepatocytes isolated from rats and humans, and iii) in vivo in rats which had received curcumin. Cytosol from intestine or liver metabolised curcumin sulphate and hexahydrocurcumin, microsomes biotransformed curcumin to curcumin glucuronide, hepatocytes metabolised curcumin to hexahydrocurcumin and hexahydrocurcuminol. Metabolic reduction of curcumin in human intestine was 18 times more abundant than that in rat intestine. When curcumin was administered by gavage, curcumin sulphate and curcumin glucuronide were detected in plasma. When rats received curcumin as a dietary constituent, only minute levels of curcumin were measured in the plasma. In a pilot study of a standardised turmeric formulation in colorectal cancer patients, curcuminoids could not be identified in the blood after doses of up to 180 mg curcuminoids per day. Curcumin sulphate and hexahydrocurcumin were generated from curcumin by isolated sulphotransferase 1A1/1A3 and equine alcohol dehydrogenase, respectively. The results demonstrate that curcumin is rapidly metabolised by human and rat hepatic and intestinal tissues, which may explain, at least in part, its poor bioavailability. In conclusion, the results support the clinical evaluation of curcumin as a colorectal cancer chemopreventive agent.
Links: http://hdl.handle.net/2381/30764
Type: Thesis
Level: Doctoral
Qualification: PhD
Rights: Copyright © the author. All rights reserved.
Appears in Collections:Theses, MRC Toxicology Unit
Leicester Theses

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