Detection of Curcumin and its metabolites in hepatic tissue and portal blood of patients following oral administration

 

Br J Cancer. 2004; 90(5):1011-5.

 

Curcumin is an effective chemopreventive agent; however it has low systemic bioavailability due to its poor absorption and avid metabolic conjugation and reduction. Despite its low bioavailability following oral administration, it has been earlier reported in rodents that Curcumin exerts biological activity on sites distant from the locus of absorption.

 

Objective:

To investigate whether oral administration of Curcumin results in concentrations of the agent in normal and malignant liver tissue, which are sufficient to elicit pharmacological activity.

 

Study Design:

12 patients with hepatic metastatic disease from primary colorectal adenocarcinomas were selected. Patients were administered 1, 4, 8 capsules (each capsule containing 450 mg of Curcumin) orally as a daily dose for 1 week prior to surgery. After 1 hour of oral consumption of Curcumin the sample of peripheral blood was collected. After 6-7 h of last dose of Curcumin, hepatic resection was performed and sample of portal blood, bile and further samples of peripheral blood was collected. Levels of Curcumin and its metabolites were measured by HPLC in portal and peripheral blood, bile and liver tissue.

 

Results:

  • In case of three patients who received 3600 mg Curcumin, their portal serum showed presence of Curcumin, Curcumin glucuronide, and Curcumin sulphate. In the peripheral blood, two patients showed a peak co eluting with Curcumin.
  • In patients who received 1800 or 450 mg of Curcumin, their peripheral and portal blood did not show the presence of Curcumin and its conjugates.
  • In all the patients who received Curcumin; their bile, normal and malignant liver tissue did not show presence of Curcumin and its conjugates. However, analysis of normal liver tissue from one patient who received 3600 mg of Curcumin daily showed the presence of hexahydrocurcumin and hexahydrocurcuminol, which are the metabolic reduction product of Curcumin.
  • In patients who had received Curcumin, levels of malondialdehyde-DNA (M1G) adduct, which reflect oxidative DNA changes were not decreased in post-treatment normal and malignant liver tissue when compared to pretreatment samples.

 

Conclusion:

It is the first evidence in humans that oral administration of Curcumin furnishes trace levels (10-8M) of parent compound and its metabolites in the liver tissue and portal circulation.

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Sabinsa Corporation is a manufacturer, supplier and marketer of herbal extracts, cosmeceuticals, minerals, dietary supplements and specialty fine chemicals for the nutritional, cosmetic, pharmaceutical and food industries.

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