Enhancement of the chemoprotective enzymes glucuronosyl transferase and glutathione transferase in specific organs of the rat by the coffee components kahweol and cafestol

Huber, Wolfgang W, Prustomersky, Sonja, Delbanco, Evert, Uhl, Maria, Scharf, Gerlinde, Turesky, Robert J, Thier, Ricarda, & Schulte-Hermann, Rolf (2002) Enhancement of the chemoprotective enzymes glucuronosyl transferase and glutathione transferase in specific organs of the rat by the coffee components kahweol and cafestol. Archives of Toxicology, 76(4), pp. 209-217.

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The coffee components kahweol and cafestol (K/C) have been reported to protect the colon and other organs of the rat against the formation of DNA adducts by 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP) and aflatoxin B1. PhIP is a cooked-food mutagen to which significant human exposure and a role in colon cancer etiology are attributed, and, interestingly, such cancers appear to develop at a lower rate in consumers of coffees with high amounts of K/C. Earlier studies in rodent liver have shown that a key role in the chemopreventive effect of K/C is likely to be due to the potential of these compounds to induce the detoxification of xenobiotics by glutathione transferase (GST) and to enhance the synthesis of the corresponding co-factor glutathione. However, mutagens like PhIP may also be detoxified by UDP-glucuronosyl transferase (UDPGT) for which data are lacking regarding a potential effect of K/C. Therefore, in the present study, we investigated the effect of K/C on UDPGT and, concomitantly, we studied overall GST and the pattern of individual GST classes, particularly GST-θ, which was not included in earlier experiments. In addition, we analyzed the organ-dependence of these potentially chemopreventive effects. K/C was fed to male F344 rats at 0.122% in the chow for 10 days. Enzyme activities in liver, kidney, lung, colon, salivary gland, pancreas, testis, heart and spleen were quantified using five characteristic substrates and the hepatic protein pattern of GST classes α, μ, and π was studied with affnity chromatography/HPLC. Our study showed that K/C is not only capable of increasing overall GST and GST classes α, μ, and π but also of enhancing UDGPT and GST-θ. All investigated K/C effects were strongest in liver and kidney, and some response was seen in lung and colon but none in the other organs. In summary, our results show that K/C treatment leads to a wide spectrum of increases in phase II detoxification enzymes. Notably, these effects occurred preferentially in the well perfused organs liver and kidney, which may thus not only contribute to local protection but also to anti-carcinogenesis in distant, less stimulated organs such as the colon.

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ID Code: 77460
Item Type: Journal Article
Refereed: Yes
Additional URLs:
Keywords: Chemoprevention, Coffee, Glutathione-S-transferase, Organ specificity, Rat, UDP-glucuronosyl transferase, cafestol, glucuronosyltransferase, glutathione transferase, kahweol, diterpene, animal experiment, animal tissue, antineoplastic activity, article, chemoprophylaxis, colon, controlled study, drug effect, enzyme activity, enzyme analysis, enzyme substrate, kidney, liver protection, lung, male, nonhuman, organ distribution, priority journal, protection, animal, antibody specificity, chemistry, digestive system, enzymology, exocrine gland, Fischer 344 rat, heart muscle, metabolism, spleen, testis, urinary tract, Diterpenes, Exocrine Glands, Myocardium, Rats, Rats, Inbred F344, Support, Non-U.S. Gov't, Animals, Animalia, Rodentia
DOI: 10.1007/s00204-002-0322-1
ISSN: 1432-0738
Divisions: Current > Schools > School of Clinical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Copyright Owner: Copyright 2002 Springer-Verlag
Deposited On: 16 Oct 2014 22:57
Last Modified: 16 Oct 2014 22:57

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