Induction of rat hepatic and intestinal UDP-glucuronosyltransferases by naturally occurring dietary anticarcinogens

Abstract

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.

Effects of Herbal Supplements on Drug Glucuronidation. Review of Clinical, Animal, andIn VitroStudies

“…As mentioned under cranberry, quercetin showed inhibition in vitro of UGT1A1 and 1A9 in addition to induction of p-nitrophenol glucuronidation in rats [44,45,48]. In a prostate cell line, both quercetin and kaempferol induced testosterone glucuronidation in vitro by 2.5-and 4-fold, respectively [46].…”

“…As mentioned, quercetin and kaempferol are substrates of UGT1A3 and UGT1A9 and in vitro modulators for UGT1A1, UGT1A9, and UGT2B17 [42][43][44][45][46]48]. However, based on flavonoid content in grape seeds of 4 to 5 %, in vivo quercetin and kaempferol concentrations are not likely to reach inhibitory levels [79].…”

Naturally Occurring Substances and Their Role in Chemo-protective Effects

“…The main sources of ferulic acid are foods such as wheat bran, but also coffee, apples, artichokes, peanuts, oranges, and pineapples. Animal studies and in vitro studies suggest that ferulic acid may have direct antitumour activity against breast and colon cancer (53)(54)(55). Ferulic acid has a significant role in the inhibition of abnormal cell proliferation in cancer cells occurring in induced carcinogenesis due to its modulatory effect on pro-apoptotic genes p53 and bcl-2 expression (56).…”

Antimutagenic Effects of Tannic Acid on Somatic and Germ Cells of Rats

“…Tannic acid is a plant polyphenol which is found, along with other condensed tannins, in several beverages including red wine, beer, coffee, black tea, green tea, and many foodstuffs such as grapes, pears, bananas, sorghum, black-eyed peas, lentils and chocolate (Erexson, 2003;Bennett et al, 2010). Similar to many polyphenols, tannic acid has been shown to possess antioxidant (Ferguson, 2001;Wu et al, 2004;Andrade et al, 2005), antimutagenic (Ferguson, 2001;Chen and Chung, 2000) and anticarcinogenic properties (Huang et al, 2010;van der Logt et al, 2003). The antioxidant mechanism of tannic acid is still far from being fully understood; therefore, it requires further investigation.…”

“…Its safe dosage ranges from 10 to 400 mg, depending on the type of food to which it is added (Chen and Chung, 2000). Also, several authors have demonstrated that tannic acid and other polyphenols have antimutagenic and anticarcinogenic activities (Ferguson, 2001;Andrade et al, 2005;Huang et al, 2010;van der Logt et al, 2003). Moreover, the consumption of polyphenol-rich fruits, vegetables, and beverages, such as tea and red wine, has been linked with inhibitory and preventive effects in various human cancers and cardiovascular diseases, which may be related-at least in part-with the antioxidant activity of polyphenols (Andrade et al, 2005).…”