RESUMEN
BACKGROUND: Gastrointestinal mucositis occurs as a consequence of cytotoxic treatment. Quercetin (QCT) is a bioflavonoid that exerts significant antioxidant activity and anti-inflammatory as well as anti-malignancy properties. OBJECTIVE: To evaluate the effects of oral QCT consumption in preventing intestinal mucosal damage and stimulating intestinal recovery following methotrexate (MTX)-induced intestinal damage in a rat model. DESIGN: Male Sprague-Dawley rats were divided into four groups: Control Group A (CONTR) - rats were treated with 2 cc of saline given by gavage for 6 days. Group B (CONTR-QCT) - rats were treated with QCT (100 mg/kg in 2 ml saline) given by gavage 3 days before and 3 days after intraperitoneal (IP) injection of saline. Group C (MTX) - rats were injected a single dose (25 mg/kg) of MTX IP. Group D (MTX-QCT) rats were treated with QCT (similar to Group B) 3 days before and 3 days after IP MTX injection. Intestinal mucosal parameters (bowel and mucosal weight, mucosal DNA and protein content, and villus height and crypt depth), enterocytes proliferation, and enterocyte apoptosis degree were investigated at sacrifice on the 4th day after MTX or saline injection. RESULTS: Administration of QCT to MTX-treated rats resulted in: (1) significant decrease in intestinal injury score, (2) significant increase in intestinal and mucosal weight in jejunum and ileum, (3) increase on the protein content of the ileum, (4) increase in the villus height in the ileum, (5) increase of crypt depth of jejunum and ileum, and (6) increase in cell proliferation in the jejunum and ileum compared to MTX-nontreated group. CONCLUSIONS: Administration of QCT prevents intestinal damage and improves intestinal recovery following MTX-induced intestinal damage in a rat. We surmise that the effect of QCT is based on induction of cell proliferation in the crypt rather than inhibition of apoptosis.
RESUMEN
BACKGROUND/AIMS: Several studies have demonstrated the antimicrobial, antihelminthic, and antioxidant potential of the active ingredients of pomegranate (PMG) extracts, suggesting their preventive and curative role in several gastrointestinal disorders. In the present study, the authors evaluated the effects of oral PMG supplementation on intestinal structural changes, enterocyte proliferation, and apoptosis during methotrexate (MTX)-induced intestinal damage in a rat. METHODS: Male rats were divided into 4 experimental groups: control rats; CONTR-PMG rats were treated with oral PMG given by gavage once a day 72 hours before and 72 hours following vehicle injection; MTX rats were treated with single dose of methotrexate; and MTX-PMG rats were treated with oral PMG following injection of MTX. Intestinal mucosal damage, mucosal structural changes, enterocyte proliferation, and enterocyte apoptosis were determined 72 hours following MTX injection. Western blotting was used to determine phosphorylated extracellular signal-regulated kinase (p-ERK) and caspase 3 protein levels. RESULTS: MTX-PMG rats demonstrated greater jejunal and ileal bowel and mucosal weights, greater jejunal and ileal mucosal DNA and protein levels, greater villus height in jejunum and ileum and crypt depth in ileum, compared with MTX animals. A significant decrease in enterocyte apoptosis in ileum of MTX-PMG rats (vs MTX) was associated with a decrease in caspase 3 protein expression as well as increased cell proliferation, which was correlated with elevated p-ERK protein levels. CONCLUSIONS: Treatment with oral PMG prevents mucosal injury and improves intestinal recovery following MTX injury in the rat.