Plant phenolic 4-coumaric acid protects against intestinal inflammation in rats.
BACKGROUND
Many plants contain significant amounts of 4-coumaric acid (4CA), a compound with antioxidant properties in vitro and in vivo. The aim of this study was to assess the effects of 4CA pretreatment on DNA oxidative stress induced by intestinal inflammation in rodents.


METHODS
4CA (50 mg/kg) was administered to rats for 14 days mixed in the diet. Colitis was induced on days 13 and 14 by administering 6% (w/v) dextran sodium sulphate (DSS) in the drinking water.


RESULTS
In the colon mucosa, DSS treatment increased myeloperoxidase activity (P < 0.05), oxidative DNA damage (P < 0.01), and cyclooxygenase-2 (COX-2) expression (P < 0.01) and reduced superoxide dismutase-2 (SOD-2) expression (P < 0.05). It was found that treatment with 4CA prior to DSS-induced inflammation reduced oxidative DNA damage (P < 0.01), COX-2 over-expression (P < 0.01) and restored SOD-2 gene expression to control levels. Similar effects were observed with nimesulide administered p.o. (5 mg/kg, 1 day before and during DSS treatment). PGE levels in plasma and colon mucosa were increased by DSS treatment and this effect was inhibited by pretreatment with 4-CA (P < 0.01).


CONCLUSIONS
Mild acute intestinal inflammation induced by DSS can be inhibited by 4-CA and this action is associated with the suppression of COX-2 expression and activity.
Luceri
C
C
Department of Pharmacology, University of Florence, IT-50139 Florence, Italy. cristina.luceri@unifi.it
Guglielmi
F
F
Lodovici
M
M
Giannini
L
L
Messerini
L
L
Dolara
P
P
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D003373:Coumaric Acids / Q000627:therapeutic use*; D051546:Cyclooxygenase 2; D004249:DNA Damage / Q000187:drug effects; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D016264:Dextran Sulfate; D015232:Dinoprostone / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D010936:Plant Extracts / Q000627:therapeutic use*; D011422:Propionates; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013482:Superoxide Dismutase / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism
D000975:Antioxidants; D003373:Coumaric Acids; D010936:Plant Extracts; D011422:Propionates; D000080242:8-Hydroxy-2'-Deoxyguanosine; D016264:Dextran Sulfate; D009195:Peroxidase; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D003849:Deoxyguanosine; D005978:Glutathione; C495469:p-coumaric acid; D015232:Dinoprostone