الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Background: Mucositis is a common debilitating side effect of chemotherapy, associated with severe small intestinal inflammation. Omega-3 fatty acids have reported as a therapeutic potential for treatment of many inflammatory conditions.
Aim of the work: The present study was performed to assess the light and electron microscopic aspects of 5-fluorouracil induced damage on different segments of small intestine and the possible protective effect of omega-3 fatty acids.
Materials and methods: 48 adult male Wister albino rats were used. The rats were randomly assigned into 3 groups: control group, FU & Omega groups. FU & Omega groups received a single intraperitoneal injection of 5-fluorouracil (5-FU) (150 mg/kg) at day 5 of the 14 day experiment. In addition, Omega group received Omega-3 treatment (1ml / animal) daily by orogastric tube from day 1 till time of sacrifice. The two groups were subdivided according to the time of sacrifice into the following subgroups; FU1& Omega1 (rats sacrificed 1 day after FU), FU3 & Omega3 (rats sacrificed 3 days after FU), FU6 & Omega6 (rats sacrificed 6 days after FU), FU9 & Omega9 (rats sacrificed 9 days after FU). Specimens from the three intestinal segments were collected and processed for light and electron microscopic examination. Histomorphometric and statistical analysis for villus height, crypt depth, thickness of submucosa & muscularis externa, goblet cell, apoptotic & mitotic counting were done in all of the studied groups.
Results: Marked histological changes were detected in the small intestine of FU1 & FU3 groups following 5-FU administration.These changes were almost similar in the three intestinal segments; however, statistically, the jejunum was the most affected. Detachment of epithelium from lamina propria; fusion, shortening, blunting and broadening of villi, cellular infiltration in lamina propria, reduction in number and depth of crypts, loss of surface epithelium, denuded villi & enlarged pale cells in the villi & crypts were observed. Statistically, there was significant decrease in the mean villus height and crypt depth for FU1and FU3 groups compared to control rats. A significant increase in the apoptotic count was observed in FU1 group compared to the control, accompanied by a significant decrease in the mitotic count. On the other hand, the small intestine of Omega-3 treated rats exhibited less damage compared to FU treated rats & displayed almost preserved appearance & structure. The mean villus height and crypt depth were significantly higher in Omega groups compared to FU groups & there was also significant decrease in the apoptotic count and a significant increase in the mitotic count in Omega groups compared to FU groups. Signs of initial recovery were detected in FU6 group such as significant increase in crypt depth that was accompanied with increased mitotic count while higher mitotic count and crypt depth were observed in omega6 group.The FU9 group almost showed full histological signs of recovery & there was no significant differences between FU9 & Omega9 groups. Compared to control, a progressive decrease in the PAS reaction was noticed in the brush border of the small intestine of FU1 and FU3 groups & the goblet cell number was relatively decreased in FU1 with more marked reduction in FU3 and this was statistically confirmed. Compared to the FU groups, a marked improvement in the PAS reaction of the brush border was observed in Omega-3 treated rats & the mean goblet cell number was significantly higher in Omega1& Omega3 groups compared to FU groups Electron microscopic examination of FU3 group revealed marked widening of the intercellular spaces and morphological alterations in intestinal epithelial cells. On the other hand, the Omega3 group showed preserved ultrastructure. The FU9 group was more or less similar to that of the control, except for few swollen mitochondria and localized widening of the intercellular space. On the other hand, the Omega9 group showed more intact ultrastructure, indicating more efficient and complete recovery.
Conclusion: Omega-3 fatty acids can protect the small intestine from 5-fluorouracil-induced cytotoxicity, ameliorates the associated injury and fastens the recovery. Therefore, it is recommended for cancer patients receiving chemotherapy.