Protective effects of dietary enrichment with docosahexaenoic acid plus protein in 5-fluorouracil-induced intestinal injury in the rat

Objective The intestinal side effects of anti-tumoural therapy can be so severe as to preclude its clinical efficacy, although the use of selected nutrients and growth factors may ameliorate the noxious effects. This study examines whether dietary supplementation with the polyunsaturated fatty acid docosahexaenoic acid (DHA) potentiates the protective action of growth hormone in the intestine and whether a synergetic effect occurs with dietary protein and DHA enrichment and growth hormone treatment. Methods Male Wistar rats were divided into nine groups and received a standard diet, or a diet supplemented with protein, or a diet supplemented with DHA, or a diet supplemented with both protein and DHA. Three days later, the rats were given 5-fluorouracil (5-FU) and treated with either growth hormone or placebo. A further group of animals fed a standard diet was not treated and served as a control group. Intestinal morphometry, proliferation and apoptosis were determined. Results Supplementing the diet with DHA prevented the negative action of 5-FU on mucosal morphometry, but protein supplementation was necessary to prevent the increased apoptosis. When growth hormone was also given with the dietary supplementation, the hypoproliferative effect of 5-FU was also prevented. Conclusion Enriching the diet with DHA protects against intestinal lesions produced by the anti-tumoural drug 5-FU but requires the joint administration of supplementary protein and growth hormone to reduce the noxious effects of 5-FU. Eur J Gastroenterol Hepatol 16:479-485 (C) 2004 Lippincott Williams Wilkins.