Enhancement of rat hepatic and gastrointestinal glutathione and glutathione S-transferases by alpha-angelicalactone and flavone.

The naturally occurring anticarcinogens flavone and alpha-angelicalactone incorporated separately and simultaneously in the diet at 0.5, 0.1, 0.05 and 0.01% w/w, were studied with respect to their effects on oesophageal, gastric, intestinal, colonic and hepatic (i) glutathione S-transferase (GST) enzyme activity, (ii) GST isozyme levels and (iii) glutathione (GSH) content in male Wistar rats. GST enzyme activity was significantly increased in the three treatment groups at one or more sites. The most substantial inductions were seen in oesophagus and stomach by 0.5% alpha-angelicalactone (1.9- and 2.3-fold respectively); and in small intestine, colon and liver by 0.5% combination diet (2.5-, 1.4- and 4.0-fold respectively). The inducing capacities declined with decreasing anticarcinogen concentrations. GST enzyme activity was induced in liver and to a lesser extent in small intestine and stomach. In general, in combination groups similar effects were seen as after treatment with alpha-angelicalactone or flavone separately. However, colonic GST enzyme activity was increased in the 0.5% combination group (1.4-fold), whereas in the corresponding flavone or alpha-angelicalactone groups no induction was observed. Concomitant changes in GST isozyme levels occurred. The involvement was the highest for GST-alpha (75%), followed by GST-mu (58%) and GST-pi (33%). Increased GSH levels were obtained in stomach and liver in all three treatment groups at various concentrations. These data demonstrate that dietary administration of flavone or alpha-angelicalactone, even at relatively low concentrations, may exert chemopreventive effects in stomach, small intestine, liver and to a lesser extent in oesophagus by enhancing the GST detoxification system, mainly by induction of GST-alpha and GST-mu isozymes. In addition, simultaneous administration of flavone and alpha-angelicalactone may result in anticarcinogenic effects in the colon by the same principle.