Intestinal anti-inflammatory activity of combined quercitrin and dietary olive oil supplemented with fish oil, rich in EPA and DHA (n-3) polyunsaturated fatty acids, in rats with DSS-induced colitis.
OBJECTIVE
Previous studies have described the intestinal anti-inflammatory effects exerted by the bioflavonoid quercitrin (QR) and by an n-3 polyunsaturated fatty acids (PUFA)-enriched diet in experimental models of rat colitis. The aim of the present study was to test if the combination of both treatments would result in an improvement in the intestinal anti-inflammatory effect achieved separately.


METHODS
Colitis was induced in female Wistar rats by incorporating dextran sodium sulfate (DSS) in drinking water at 5% (w/v) for 5 days and at 2% (w/v) for the following 10 days. Five groups of rats (n=10) were used: two of them received an olive-oil-based diet with fish oil, rich in n-3 PUFA (FO diet) for 2 weeks before colitis induction and until the end of the experiment, and one of those also was administered daily QR (1mg/kg, PO), starting when DSS concentration was changed. DSS colitis was induced in other two groups fed with standard rat diet, one of them being administered QR as before. A non-colitic group fed standard diet was also included. After that period, the rats were sacrificed and colonic damage was assessed both histologically and biochemically.


RESULTS
The concurrent administration of FO diet and QR exhibited an intestinal anti-inflammatory effect, as evidenced by a significant improvement of all biochemical parameters of colonic inflammation assayed in comparison with non-treated colitic rats. Thus, both colonic myeloperoxidase (MPO) and alkaline phosphatase (AP) activities were significantly reduced compared with untreated colitic rats. In addition, a complete restoration of colonic glutathione content, which was depleted as a consequence of the colonic insult, was obtained in rats treated with QR plus FO diet; this content was even higher than that obtained when colitic rats were treated with FO diet alone. When compared with the control colitic group, the combined treatment was also associated with a lower colonic nitric oxide synthase and cyclooxygenase-2 expression as well as with a significant reduction in different colonic proinflammatory mediators assayed, i.e. leukotriene B(4), tumor necrosis factor alpha and interleukin 1beta, showing a significantly greater inhibitory effect of the latter in comparison with rats receiving FO diet without the flavonoid.


CONCLUSIONS
These results support the potential synergism between the administration of the flavonoid and the incorporation of olive oil and n-3 PUFA to the diet for the treatment of these intestinal inflammatory disorders.
Camuesco
D
D
Department of Pharmacology School of Pharmacy, University of Granada, Campus Universitario 'La Cartuja' s/n, 18071 Granada, Spain.
Comalada
M
M
Concha
A
A
Nieto
A
A
Sierra
S
S
Xaus
J
J
Zarzuelo
A
A
Gálvez
J
J
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D003106:Colon / Q000201:enzymology / Q000473:pathology; D016264:Dextran Sulfate; D004032:Diet; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000008:administration & dosage; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D005260:Female; D005395:Fish Oils / Q000008:administration & dosage* / Q000737:chemistry; D007700:Kinetics; D000069463:Olive Oil; D009195:Peroxidase / Q000378:metabolism; D010938:Plant Oils / Q000008:administration & dosage*; D011794:Quercetin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D051381:Rats; D017208:Rats, Wistar
D000893:Anti-Inflammatory Agents; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D000069463:Olive Oil; D010938:Plant Oils; D004281:Docosahexaenoic Acids; C012526:quercitrin; D016264:Dextran Sulfate; D011794:Quercetin; D015118:Eicosapentaenoic Acid; D009195:Peroxidase; D000469:Alkaline Phosphatase