Fig seed oil improves intestinal damage caused by 5-FU-induced mucositis in rats

Abstract

Intestinal mucositis poses a significant concern associated with cancer therapy. This study aims to investigate the protective and/or healing effect of fig seed oil (FSO) on 5-fluorouracil (5-FU)-induced intestinal mucositis by targeting inflammatory markers and histologic changes in rats. Albino Wistar adult rats were randomly divided into four groups, including three male and three female animals. All the animals in the four groups had a normal standard diet and water throughout the experimental period, which lasted up to 11 days. Rats were administered FSO 0.6 mL (mucositis FSO group) and FSO 0.2 mL (mucositis FSO-R group) daily throughout the experiment. These two groups and one additional group (mucositis group) were given an intraperitoneal injection of 5-FU (300 mg/kg) on Day 5 of the experiment. In contrast, the fourth group (Control group) was given an intraperitoneal saline injection on Day 5 of the experiment. FSO treatment ameliorated 5-FU-induced intestinal mucositis. On immunohistologic examination, FSO suppressed significantly the activation of NF-κB and expression of IL-β and TNF-α of the harvested intestinal tissue. The reduced dose FSO (mucositis FSO-R) was as effective as the full dose (mucositis FSO) in suppressing IL-β and TNF-α production, but was not as effective as the full dose in suppressing NF-κB. On light microscopy, FSO attenuated significantly 5-FU-induced anomalies, such as the reduction of intestinal villus length and Goblet cell count. The reduced dose FSO (mucositis FSO-R) was as effective as the full dose (mucositis FSO) in restoring villus length, but was not as effective as the full dose in restoring Goblet cell count. The findings of the study suggest that FSO inhibits 5-FU-induced intestinal mucositis via modulation of mucosal inflammation.

Keywords: chemotherapy; fig seed oil; fluorouracil; mucositis.

FIGURE 1

5‐FU administered on the fifth day significantly induced body weight loss in all three mucositis groups. Weight reduction reached the maximum level on the eighth day and resumed afterward.

FIGURE 2

Evaluation of the villus length in 5‐FU‐induced mucositis. There was a statistical difference between the control and all three mucositis groups. To delineate the healing effect of FSO, we compared the mucositis group with mucositis FSO (p < .0001) and mucositis FSO‐R (p < .0001) groups and found statistically significant differences in terms of the villus length. There was no statistical difference between mucositis FSO and mucositis FSO‐R groups. So, even the reduced dose (three times less) of FSO improved the villus length nearly as much as the full FSO dose.

FIGURE 3

Histological samples from all the groups (the first column is hematoxylin + eosin, the second column is periodic acid–Schiff staining): (a‐a1) control group, (b‐b1) mucositis group, (c‐c1) mucositis FSO group, (d‐d1) mucositis FSO‐R group. The white arrows in the first column indicate the length of the villus sampled in the section. The black arrows in the second column indicate the distribution of Goblet cells. The red arrows and the star in the control group show epithelial shedding and vacuolization, respectively. Both are other typical features of mucosal damage.

FIGURE 4

Evaluation of the Goblet cell counts in 5‐FU‐induced mucositis A statistically significant difference was observed between the control and mucositis and mucositis FSO‐R groups. No difference was found between the control and mucositis FSO groups. To further delineate the healing effect of FSO, we compared the mucositis group with two FSO groups and found significant difference in only one comparison (mucositis vs. mucositis FSO, p < .014) in terms of the Goblet cell counts. So, premedication with oral FSO leads to a nearly full recovery of Goblet cell count, which was proven statistically in the mucositis FSO group (i.e., full dose of FSO) only.

FIGURE 5

Evaluation of the expression of three well‐known inflammation markers, IL‐β, TNF‐α, and NF‐κB, in the harvested intestinal specimens. (a) There was a statistical difference between the mucositis and mucositis FSO groups (p < .01), and between the mucositis and mucositis FSO‐R groups (p < .01) in terms of the IL‐β values. No difference was found between the mucositis FSO and mucositis FSO‐R. (b) There was a statistically significant difference between the mucositis and mucositis FSO groups (p < .005), and between the mucositis and mucositis FSO‐R (p < .005) groups in terms of the TNF‐α values. No difference was found between the mucositis FSO and mucositis FSO‐R. (c) A statistical difference was observed between the mucositis and mucositis FSO groups (p < .005), between the mucositis and mucositis FSO‐R groups (p < .05), and between the mucositis FSO and mucositis FSO‐R groups (p < .05) in terms of the NF‐κB values. The reduced dose (three times less) of FSO, however, did not suppress the NF‐κB production as powerful as the full FSO dose.