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.
Guglielmi
Francesco
F
Department of Pharmacology, University of Florence, viale Pieraccini 6, 50139 Florence, Italy. francesco.guglielmi@unifi.it
Luceri
Cristina
C
Giovannelli
Lisa
L
Dolara
Piero
P
Lodovici
Maura
M
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D003106:Colon / Q000378:metabolism*; D020552:Comet Assay; D003373:Coumaric Acids / Q000494:pharmacology*; D004249:DNA Damage / Q000187:drug effects*; D005982:Glutathione Transferase / Q000378:metabolism; D062385:Hydroxybenzoates / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D011422:Propionates; D051381:Rats; D011916:Rats, Inbred F344; D014810:Vitamin E / Q000378:metabolism / Q000494:pharmacology
D000975:Antioxidants; D003373:Coumaric Acids; D062385:Hydroxybenzoates; D007527:Isoenzymes; D011422:Propionates; D014810:Vitamin E; C009091:protocatechuic acid; D005982:Glutathione Transferase; C412602:glutathione S-transferase Mu 2; C495469:p-coumaric acid