Polysaccharides from Passion Fruit Peels: From an Agroindustrial By-Product to a Viable Option for 5-FU-Induced Intestinal Damage

Abstract

Gastrointestinal mucositis is a serious and dose-limiting toxic side effect of oncologic treatment. Interruption of cancer treatment due to gastrointestinal mucositis leads to a significant decrease in cure rates and consequently to the deterioration of a patient's quality of life. Natural polysaccharides show a variety of beneficial effects, including a gastroprotective effect. Treatment with soluble dietary fiber (SDF) from yellow passion fruit (Passiflora edulis) biomass residues protected the gastric and intestinal mucosa in models of gastrointestinal injury. In this study, we investigated the protective therapeutic effect of SDF on 5-FU-induced mucositis in male and female mice. Oral treatment of the animals with SDF did not prevent weight loss but reduced the disease activity index and preserved normal intestinal function by alleviating diarrhea and altered gastrointestinal transit. SDF preserved the length of the colon and histological damage caused by 5-FU. SDF significantly restored the oxidative stress and inflammation in the intestine and the enlargement and swelling of the spleen induced by 5-FU. In conclusion, SDF may be a promising adjuvant strategy for the prevention and treatment of intestinal mucositis induced by 5-FU.

Keywords: 5-FU; Passiflora edulis; agroindustrial by-products; agroindustrial residues; chemotherapy damage; intestinal damage; intestinal injury.

Figure 1

Effect of orally administered SDF on body weight loss, disease activity index, colon length, and intestinal motility in 5-FU-induced intestinal mucositis in female (A–D) and male (E–H) mice. * Difference from 5-FU group, # difference from control group to p < 0.05.

Figure 2

Effect of orally administered SDF on spleen and liver weights in 5-FU-induced intestinal mucositis in female (A,B) and male (C,D) mice. * Difference from 5-FU group, # difference from control group to p < 0.05.

Figure 3

Effect of orally administered SDF on GSH and GST levels in 5-FU-induced intestinal mucositis in female (A–D) and male (E–H) mice. * Difference from 5-FU group, # difference from control group to p < 0.05.

Figure 4

Effect of orally administered SDF on MPO and NAG activities and IL-1β levels in 5-FU-induced intestinal mucositis in female (A–F) and male (G–L) mice. * Difference from 5-FU group, # difference from control group to p < 0.05.

Figure 8

Effect of orally administered SDF on Paneth cells of duodenum in 5-FU-induced intestinal mucosal inflammation in female and male mice (H&E). * Difference from 5-FU group, # difference from control group to p < 0.05. Images show: (A) Paneth cells/crypt; (B) number of granules/Paneth cells; (C) area with Paneth cells/crypt (µm2); (D) Paneth cells in crypt (relative percentage); (E–J) small intestine sections stained with H&E (hematoxylin and eosin) (15 µm). C-F: Control group (female), 5-FU-F: 5-FU group (female), SDF-F: SDF group (female), C-M: Control group (male), 5-FU-M: 5-FU group (male), SDF-M: SDF group (male). Arrows: Paneth cells.

Figure 9

Effect of orally administered SDF on histological analysis of colon goblet cells in 5-FU induced intestinal mucositis in female and male mice (PAS and Alcien Blue). * Difference from 5-FU group, # difference from control group to p < 0.05. Images show (A) colon stained with PAS (pixel/field); (B) colon stained with Alcian blue (pixel/field); (C–H) colon sections stained with PAS-AB (100 µm). C-F: Control group (female), 5-FU-F: 5-FU group (female), SDF-F: SDF group (female), C-M: Control group (male), 5-FU-M: 5-FU group (male), SDF-M: SDF group (male). Arrows: goblet cells.

Figure 10

Effect of orally administered SDF on colon histopathological analysis in 5-FU -induced intestinal mucosal inflammation in female and male mice (H&E). * Difference from 5-FU group, # difference from control group to p < 0.05. Images show: (A) Muscular (µm); (B) Submucosa (µm); (C) Mucosa (µm); (D) Crypts width (µm); (E) Crypts depth (µm); (F) colon sections stained with H&E (hematoxylin and eosin) (100 µm). C-F: Control group (female), 5-FU-F: 5-FU group (female), SDF-F: SDF group (female), C-M: Con-trol group (male), 5-FU-M: 5-FU group (male), SDF-M: SDF group (male). Brackets: thickness of the tissue layers (mucosa and submucosa).

Figure 11

Effect of orally administered SDF on colon histopathological analysis in 5-FU-induced intestinal mucosal inflammation in female and male mice (H&E). # difference from control group to p < 0.05. Images show: (A) Inflammatory infiltrates (score); (B) Histoarchitecture loss (score); (C) Cryptitis (score); (D) Sections of colon (100 µm) stained with H&E (hematoxylin and eosin). C-F: Control group (female), 5-FU-F: 5-FU group (female), SDF-F: SDF group (female), C-M: Control group (male), 5-FU-M: 5-FU group (male), SDF-M: SDF group (male). Arrows: loss of mucosal architecture, #: inflammatory infiltrate and abscess formation in crypts (cryptitis).

Figure 5

Effect of orally administered SDF on duodenal histological PAS and AB staining of female and male mice. * Difference from 5-FU group, # difference from control group to p < 0.05. Images show (A) Duodenum stained with PAS (pixel/field); (B) Colon stained with Alcian blue (pixel/field); (C–H) Duodenum stained with PAS-AB (100 µm). C-F: Control group (female), 5-FU-F: 5-FU group (female), SDF-F: SDF group (female), C-M: Control group (male), 5-FU-M: 5-FU group (male), SDF-M: SDF group (male). Arrows: goblet cells.

Figure 6

Effect of orally administered SDF on histomorphometry analysis of duodenum in 5-FU—induced intestinal mucosal inflammation in female and male mice (H&E). * Difference from 5-FU group, # difference from control group to p < 0.05. Images show (A) Muscular (µm); (B) Submucosa (µm); (C) Mucosa (µm); (D) Villus-crypt ratio; (E) Crypts depth (µm); (F) Crypts width (µm); (G) Villus height (µm); (H) Villus width (µm); (I–N) duodenum sections (100 µm) stained with H&E (hematoxylin and eosin). C-F: Control group (female), 5-FU-F: 5-FU group (female), SDF-F: SDF group (female), C-M: Control group (male), 5-FU-M: 5-FU group (male), SDF-M: SDF group (male). Brackets: thickness of the tissue layers (mucosa and submucosa).

Figure 7

Effect of orally administered SDF on duodenal histopathological analysis in 5-FU -induced intestinal mucosal inflammation in female and male mice (H&E). # difference from control group to p < 0.05. Images show (A) Inflammatory infiltrate (score); (B) loss of histoarchitecture (score); (C) Cryptitis (score); (D–I) duodenum stained with H&E (hematoxylin and eosin) (100 µm). # different from control group to p < 0.05. C-F: Control group (female), 5-FU-F: 5-FU group (female), SDF-F: SDF group (female), C-M: Control group (male), 5-FU-M: 5-FU group (male), SDF-M: SDF group (male). Arrows: loss of mucosal architecture, #: inflammatory infiltrate and abscess formation in crypts (cryptitis).

Figure 12

Representative image of the experimental protocol for the induction of intestinal mucosal inflammation.