Effects of dietary curcumin on glutathione S-transferase and malomdialdehyde-DNA adducts in rat liver and colon mucosa: Relationship with drug levels

Curcumin prevents colon cancer in rodent models, It inhibits lipid peroxida tion and cyclooxygenase-2 (COX-2) expression and induces glutathione S-tran sferase (GST) enzymes, We tested the hypothesis that 14 days of dietary cur cumin (2%) affects biomarkers relevant to cancer chemoprevention in the rat , Levels of inducible COX-2, as reflected by prostaglandin E, production by blood leukocytes, were measured ex vivo, Total GST activity and adducts of malondialdehyde with DNA. (M(1)G), which reflect endogenous lipid peroxida tion, were measured in colon mucosa, liver, and blood leukocytes. Curcumin and its metabolites were analyzed by high-performance Liquid chromatography in plasma, and its pharmacokinetics were compared following a diet contain ing 2% curcumin versus intragastric (i,g,) administration of curcumin suspe nded in an amphiphilic solvent, The curcumin diet did not alter any of the markers in the blood but increased hepatic GST by 16% and decreased colon M ,G levels by 36% when compared with controls. Administration of carbon tetr achloride during the treatment period increased colon M,G levels, and this increase was prevented by dietary curcumin, Dietary curcumin yielded low dr ug levels in the plasma, between 0 and 12 nM, whereas tissue concentrations of curcumin in Liver and colon mucosa were 0.1-0.9 nmol/g and 0.2-1.8 mu m ol/g, respectively, In comparison with dietary administration, suspended cu rcumin given i,g, resulted in more curcumin in the plasma but much less in the colon mucosa, The results show that curcumin mixed,vith the diet achiev es drug levels in the colon and liver sufficient to explain the pharmacolog ical activities observed and suggest that this mode of administration may b e preferable for the chemoprevention of colon cancer.