Oral administration of short‐chain fatty acids reduces the intestinal mucositis caused by treatment with Ara‐C in mice fed commercial or elemental diets

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Abstract
Swiss mice fed commercial or elemental diets and an oral short‐chain fatty acid (SCFA) solution or saline were treated with the cytostatic drug Ara‐C (cytarabine, 3.6 mg/mouse/day) for two or four days. Histopathological examination revealed less damage (atrophy, inflammation, or necrosis) to the small intestine and colon caused by Ara‐C when SCFA was administered. Accordingly, protein and nucleotide concentrations in the intestinal mucosa were higher in the group receiving SCFA than in the group receiving a placebo of the same pH and osmolarity. Improvement by SCFA treatment was correlated with an increase in the height of the intestinal villi, with no alterations of the crypts. Furthermore, the number of intraepithelial lymphocytes was similar to normal values in animals receiving SCFA and Ara‐C. When large doses of SCFA were administered, xanthomized enterocytes appeared, suggesting an accumulation of fatty acids in these cells. We conclude that oral administration of SCFA at close to physiological proportions reduces the inflammation and necrosis caused by Ara‐C administration, thus representing a potential factor for the improvement of patients with mucositis caused by cancer treatment.