Induction of rat hepatic and intestinal UDP-glucuronosyltransferases by naturally occurring dietary anticarcinogens.
Gastrointestinal tumours are among the most common malignancies in Western society, the majority of which are associated with dietary and lifestyle factors. Many dietary or lifestyle factors have been identified which may have toxic or carcinogenic properties. However, several dietary compounds also able to reduce gastrointestinal cancer rates in both humans and animals have been characterized. Though the exact mechanism leading to the anticarcinogenic action of these compounds is not fully known, it has been demonstrated that this chemopreventive capacity may be due to elevation of the glutathione S-transferase detoxification enzymes. Here we have investigated the effect of several anticarcinogens on the gastrointestinal UDP-glucuronosyltransferase (UGT) enzymes. Diets of male Wistar rats were supplemented with ellagic acid, ferulic acid, Brussels sprouts, quercetin, alpha-angelicalactone, tannic acid, coumarin, fumaric acid, curcumin and flavone, separately, and combinations of alpha-angelicalactone and flavone. Hepatic and intestinal (proximal, mid and distal small intestine and colon) UGT enzyme activities were quantified using 4-nitrophenol and 4-methylumbelliferone as substrates. All anticarcinogens tested increased UGT enzyme activity with both substrates, at one at least of the five different sites investigated. alpha-Angelicalactone, coumarin and curcumin showed enhanced UGT enzyme activities at all five sites. Both small and large intestinal UGT enzyme activities were increased by quercetin, alpha-angelicalactone, coumarin, curcumin and flavone. Except for tannic acid, all agents induced hepatic UGT enzyme activity. Furthermore, dietary administration of alpha-angelicalactone and flavone, given individually or in combination, enhanced the UGT detoxification system in the liver and, to a lesser extent, in intestine. In conclusion, induction of gastrointestinal UGT enzyme activities after consumption of dietary anticarcinogens may contribute to a better detoxification of potentially carcinogenic compounds and subsequently to the prevention of gastrointestinal cancer.
van der Logt
E M J
EM
Department of Gastroenterology, University Medical Centre St Radboud, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
Roelofs
H M J
HM
Nagengast
F M
FM
Peters
W H M
WH
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D004032:Diet; D004790:Enzyme Induction / Q000187:drug effects*; D014453:Glucuronosyltransferase / Q000187:drug effects* / Q000378:metabolism; D007422:Intestines / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar
D016588:Anticarcinogenic Agents; D014453:Glucuronosyltransferase