Effects of dietary anticarcinogens and nonsteroidal anti-inflammatory drugs on rat gastrointestinal UDP-glucuronosyltransferases.
BACKGROUND
Dietary compounds or nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce cancer rates. Elevation of phase II detoxification enzymes might be one of the mechanisms leading to cancer prevention. We investigated the effects of dietary anticarcinogens and NSAIDs on rat gastrointestinal UDP-glucuronosyltransferases (UGT).


METHODS
Diets of Wistar rats were supplemented with oltipraz, alpha-tocopherol, beta-carotene, phenethylisothiocyanate (PEITC), sulforaphane analogue compound-30, indole-3-carbinol, D-limonene, relafen, indomethacin, ibuprofen, piroxicam, acetyl salicylic acid or sulindac. Hepatic and intestinal UGT enzyme activities were quantified by using 4-nitrophenol and 4-methylumbelliferone as substrates.


RESULTS
Compound-30, D-limonene, indomethacin, ibuprofen or sulindac enhanced proximal small intestinal UGT activities. Only compound-30 was able to induce mid- and distal small intestinal UGT activities. Large intestinal UGT activities were increased by ibuprofen and sulindac, whereas oltipraz, PEITC and D-limonene gave enhanced hepatic UGT activities.


CONCLUSIONS
Mainly rat proximal small intestinal and hepatic UGT enzyme activities were induced by dietary anticarcinogens or NSAIDs. Enhanced UGT activities might lead to a more efficient detoxification of carcinogenic compounds and thus could contribute to the prevention of gastrointestinal cancer.
Van der Logt
Elise M J
EM
Department of Gastroenterology, University Medical Centre St Radboud, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
Roelofs
Hennie M J
HM
van Lieshout
Esther M M
EM
Nagengast
Fokko M
FM
Peters
Wilbert H M
WH
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D019587:Dietary Supplements; D004790:Enzyme Induction / Q000187:drug effects; D014453:Glucuronosyltransferase / Q000096:biosynthesis / Q000378:metabolism*; D006923:Hymecromone / Q000378:metabolism; D007421:Intestine, Small / Q000187:drug effects / Q000201:enzymology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D009596:Nitrophenols / Q000378:metabolism; D051381:Rats
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016588:Anticarcinogenic Agents; D009596:Nitrophenols; D006923:Hymecromone; C021788:4-methylumbelliferone glucuronyltransferase; D014453:Glucuronosyltransferase; C024836:4-nitrophenol