Tranilast Treatment Prevents Chronic Radiation-Induced Colitis in Rats by Inhibiting Mast Cell Infiltration.

INTRODUCTION: Mast cells are the principal cells involved in acute and chronic colitis due to radiation, known as radiation-induced colitis (RIC). In this study, we investigated whether pretreatment with tranilast, a mast cell inhibitor, could alleviate chronic RIC. METHODS: A total of 23 Sprague-Dawley rats were randomly divided into three groups: control group (n = 5), radiation group (RG, n = 9), and tranilast-pretreated radiation group (TG, n = 9). The rats in the RG and the TG were irradiated in the pelvic area (1.5 cm from the anus) with a single dose of 20 Gy under general anesthesia. Tranilast (100 mg/kg) was administered intraperitoneally to the rats of the TG for 10 days, starting from the day of pelvic radiation. Ten weeks after radiation, the rats were euthanized. Rectal tissue samples were histologically evaluated for the total inflammation score (TIS) and mast cell count. The expression of MUC2, MUC5AC, and matrix metalloproteinase-9 (MMP-9) was also assessed immunohistochemically. RESULTS: Both the TIS and specific components of TIS such as epithelial atypia, vascular sclerosis, and colitis cystica profunda (CCP) were significantly higher in the RG than in the TG (p = 0.02, 0.038, 0.025, and 0.01, respectively). Thein number of infiltrating mast cells was significantly higher in the RG than in the TG (median [range]: 20 [3-54] versus 6 [3-25], respectively; p = 0.034). Quantitatively, the number of MMP-9-positive cells was significantly higher in the RG (23.67 ± 19.00) than in the TG (10.25 ± 8.45) (mean ± standard deviation; p < 0.05). TIS and MMP-9 exhibited a strong association (correlation coefficient r = 0.56, p < 0.05). Immunohistochemically, the mucin-lake of CCP showed no staining for MUC5AC but was stained positive for MUC2. CONCLUSION: Tranilast pretreatment of chronic RIC showed an anti-inflammatory effect associated with the reduction of mast cell infiltration and MMP-9 expression.

Flavonoids protect colon against radiation induced colitis.

Radiation induced colitis is one the most common clinical issue for patients receiving radiotherapy. For this reason, we aimed to investigate the effect of antioxidant-effective flavonoids hesperidin and quercetin on the intestinal damage induced by radiation in this study. TNF-alpha, interleukin-10 (IL-10), heat shock protein 70 (HSP 70) and caspase 3, 8, 9 markers of apoptotic pathways were measured in the colon tissues of irradiated acute intestinal damage by enzyme-linked immunosorbent assay (ELISA). Irradiation of rats caused a significance increase of TNF-alpha, caspase 3/8/9 and decrease of IL-10 concentrations. Hesperidin and quercetin treatment resulted in decreased levels of TNF-alpha and increased levels of IL-10. Quercetin significantly decreased caspase 3/8/9 levels. Hesperidin produced a decreased of caspase 3/8/9 levels compared with irradiation group but this was statistically not significant. Only significant alteration of HSP 70 were seen in hesperidin treated rats. Further studies are needed to elucidate the mechanism by which flavonoids induced signaling provides protection against apoptosis and inflammation.

Prophylactic and therapeutic effects of oral budesonide for acute radiation-induced enteritis and colitis in rats.

No satisfactory means has been found to control the symptoms of diarrhea and weight loss caused by radiation-induced enteritis and colitis. As a glucocorticoid, budesonide has multiple effects, and this study aimed to test whether it could be effective in treating these symptoms. Twenty-eight male Wistar albino rats were randomly allocated into 4 groups. Group I received 0.1 mg/kg/day budesonide at 8-h intervals for 5 days and did not undergo radiation. Group II received 0.1 mg/kg/day budesonide at 8-h intervals for 1 day before radiation treatment and 4 days after irradiation. Group III received 0.1 mg/kg/day budesonide at 8-h intervals for 4 days after irradiation. Group IV received only radiation treatment. On the fifth day after radiation treatment, the rats underwent laparotomy. The rats were weighed before irradiation and before laparotomy. Because of diarrhea, all rats lost weight except group I, which showed weight gain. Weight loss was statistically significant only in group IV. Group I rats exhibited a normal jejunum, ileum, and colon. The other groups showed varying degrees of damage. We conclude that, particularly when given before irradiation, budesonide decreased the side effects of radiation-induced enteritis and colitis both clinically and morphologically. Future pathophysiological and clinical studies will be needed to support this result.