Rebamipide Attenuates 5-Fluorouracil-Induced Small Intestinal Mucositis in a Mouse Model

Kim, Hyun Jin; Kim, Jin Hyun; Moon, Won; Park, Jongha; Park, Seun Ja; Song, Geun Am; Han, Seung Hee; Lee, Jong Hun

doi:10.1248/bpb.b14-00400

Cited by 22 publications

(14 citation statements)

References 15 publications

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“…Our findings are consistent with those presented in these studies. It is during the ulceration phase where atrophic changes are visible including the lesion of the intestinal epithelium, a characteristic of mucositis [7,11,40].…”

Section: Discussionmentioning

confidence: 99%

“…Intestinal mucositis, characterized by inflammatory and/or ulcerative process in the gastrointestinal tract, is a result of cellular and tissue damage caused by 5-fluorouracil antimetabolite treatment [3]. Based on the number of chemotherapy cycles, 5-FU dose, schedule, patient's age, sex, and nutritional status [4,5], the incidences of mucositis in cancer patients range from 40 to 100% [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

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Troxerutin Prevents 5-Fluorouracil Induced Morphological Changes in the Intestinal Mucosa: Role of Cyclooxygenase-2 Pathway

et al. 2020

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Intestinal mucositis is a common complication associated with 5-fluorouracil (5-FU), a chemotherapeutic agent used for cancer treatment. Troxerutin (TRX), a semi-synthetic flavonoid extracted from Dimorphandra gardneriana, has been reported as a potent antioxidant and anti-inflammatory agent. In the present study, we aimed to evaluate the effect of TRX on 5-FU-induced intestinal mucositis. Swiss mice were randomly divided into seven groups: Saline, 5-FU, TRX-50, TRX-100, TRX-150, Celecoxib (CLX), and CLX + TRX-100. The weight of mice was measured daily. After treatment, the animals were euthanized and segments of the small intestine were collected to evaluate histopathological alterations (morphometric analysis), levels of malondialdehyde (MDA), myeloperoxidase (MPO), glutathione (GSH), mast and goblet cell counts, immunohistochemical analysis, and cyclooxygenase-2 (COX-2) activity. Compared to the saline treatment, the 5-FU treatment induced intense weight loss and reduction in villus height. TRX treatment (100 mg/kg) prevented the 5-FU-induced histopathological changes and decreased oxidative stress by decreasing the MDA levels and increasing GSH concentration. TRX attenuated inflammatory process by decreasing MPO activity, intestinal mastocytosis, and COX-2 expression. TRX also reversed the depletion of goblet cells. Our findings suggest that TRX at a concentration of 100 mg/kg had chemopreventive effects on 5-FU-induced intestinal mucositis via COX-2 pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Troxerutin Prevents 5-Fluorouracil Induced Morphological Changes in the Intestinal Mucosa: Role of Cyclooxygenase-2 Pathway

et al. 2020

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“…Intestinal mucositis is characterized by inflammatory and/or ulcerative processes in the gastrointestinal tract, resulting in cellular and tissue damage caused by 5-FU treatment [12]. Notably, the incidence of mucositis in cancer patients ranges between 40 and 100% [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Role of Rutin in 5-Fluorouracil-Induced Intestinal Mucositis: Prevention of Histological Damage and Reduction of Inflammation and Oxidative Stress

et al. 2020

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Intestinal mucositis, characterized by inflammatory and/or ulcerative processes in the gastrointestinal tract, occurs due to cellular and tissue damage following treatment with 5-fluorouracil (5-FU). Rutin (RUT), a natural flavonoid extracted from Dimorphandra gardneriana, exhibits antioxidant, anti-inflammatory, cytoprotective, and gastroprotective properties. However, the effect of RUT on inflammatory processes in the intestine, especially on mucositis promoted by antineoplastic agents, has not yet been reported. In this study, we investigated the role of RUT on 5-FU-induced experimental intestinal mucositis. Swiss mice were randomly divided into seven groups: Saline, 5-FU, RUT-50, RUT-100, RUT-200, Celecoxib (CLX), and CLX + RUT-200 groups. The mice were weighed daily. After treatment, the animals were euthanized and segments of the small intestine were collected to evaluate histopathological alterations (morphometric analysis); malondialdehyde (MDA), myeloperoxidase (MPO), and glutathione (GSH) concentrations; mast and goblet cell counts; and cyclooxygenase-2 (COX-2) activity, as well as to perform immunohistochemical analyses. RUT treatment (200 mg/kg) prevented 5-FU-induced histopathological changes and reduced oxidative stress by decreasing MDA concentrations and increasing GSH concentrations. RUT attenuated the inflammatory response by decreasing MPO activity, intestinal mastocytosis, and COX-2 expression. These results suggest that the COX-2 pathway is one of the underlying protective mechanisms of RUT against 5-FU-induced intestinal mucositis.

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“…Rebamipid demonstrated its protective effects in several experimental models including 5 FU induced mucositis by attenuating diarrhea and preventing damage of intestinal epitheliocytes. These effects were attributable to an attenuation of 5 FU induced elevation of transforming growth factor β (TGF-beta) [ 31 , 32 ].…”

Section: Introductionmentioning

confidence: 99%

The Lactobacillus brevis 47 f Strain Protects the Murine Intestine from Enteropathy Induced by 5-Fluorouracil

et al. 2020

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We report that the results of our study indicate that Lactobacillus brevis 47 f strain isolated from the faeces of a healthy individual prevents the manifestations of experimental mucositis induced by treatment of Balb/c mice with the anticancer drug 5-fluorouracil (5 FU; 100 mg/kg i.p. × 3 days). The presence of damage to the intestine and the colon was determined by a morphometric analysis of specimens including the height of villi, the amount of goblet cells and infiltrating mononuclear cells, and the expression of the proliferative Ki-67 antigen. Changes in the lipid peroxidation in the blood and the intestine were determined by severalfold increase of the concentration of malonic dialdehyde. Oral administration of L. brevis 47 f strain prior to 5 FU decreased the drug-induced morphological and biochemical changes to their respective physiological levels; the ability of intestinal epitheliocytes to express Ki-67 was partially restored. These effects of L. brevis 47 f strain were more pronounced or similar to those of the reference compound Rebamipid, a quinoline derivative known to protect the gut from drug-induced toxicity. Thus, the new lactobacilli strain attenuates the severity of 5 FU-induced enteropathy.

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Rebamipide Attenuates 5-Fluorouracil-Induced Small Intestinal Mucositis in a Mouse Model

Cited by 22 publications

References 15 publications

Troxerutin Prevents 5-Fluorouracil Induced Morphological Changes in the Intestinal Mucosa: Role of Cyclooxygenase-2 Pathway

Troxerutin Prevents 5-Fluorouracil Induced Morphological Changes in the Intestinal Mucosa: Role of Cyclooxygenase-2 Pathway

Role of Rutin in 5-Fluorouracil-Induced Intestinal Mucositis: Prevention of Histological Damage and Reduction of Inflammation and Oxidative Stress

The Lactobacillus brevis 47 f Strain Protects the Murine Intestine from Enteropathy Induced by 5-Fluorouracil

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