Effect of 4-coumaric and 3,4-dihydroxybenzoic acid on oxidative DNA damage in rat colonic mucosa.

The effect of 4-coumaric and 3,4-dihydroxybenzoic (protocatechuic) acid on the basal oxidative DNA damage of rat colonic mucosa in vivo was studied, relative to vitamin E. F344 rats were treated with 4-coumaric or protocatechuic acid mixed in the diet (25 or 50 mg/kg for 2 weeks). It was observed that 4-coumaric acid (50 mg/kg) significantly decreased the basal level of the oxidative damage assessed as 8-OH-2'-deoxyguanosine levels in DNA and by the comet assay. Moreover, it was found that vitamin E (10 mg/kg) had no effect on colonic mucosa oxidation damage, whereas at a higher dose (55 mg/kg) it actually enhanced oxidative stress. The effect of 4-coumaric acid (50 mg/kg) on the expression of some glutathione-related enzymes (glutathione-S-transferase (GST)-P, GST-M2, GST-M1, gamma-glutamylcysteine synthetase, glutathione peroxidase (GSPX)1 and GSPX4) was also investigated at the level of the colonic mucosa. Only the expression of GST-M2 was significantly induced by 4-coumaric acid, while protocatechuic acid was inactive. The data suggest that 4-coumaric acid acts as an antioxidant in the colonic mucosa in vivo.