Effect of simvastatin in attenuation of mucositis induced by methotrexate in rats

Abstract

Purpose: Based on studies that have attributed anti-inflammatory properties to statins, the aim of this work was to observe the effect of simvastatin in the attenuation of mucositis induced by methotrexate in the gastrointestinal tract in rats and its effects on cytokines. Methods: Twelve Wistar rats weighing 270±18 g were randomly distributed into two groups: methotrexate/saline (MTX/S n = 6) and methotrexate/simvastatin (MTX /SV n=6). In all animals, 3 mg / kg of methotrexate was injected subcutaneously for 3 consecutive days. In the MTX / SV simvastatin was administered orally one week before and during treatment with methotrexate. In the MTX/S, saline was administered at the same doses and schedules. We determined the plasma levels of TNF-?, IL-1? and IL-6 and the histological analysis by HE staining in segments of esophagus, stomach, duodenum, jejunum and colon. Results: The expression of TNF-?, IL-1? and IL-6 (14±91.7, 119.3±4 and 83.1±4, respectively) was lower in the MTX/SV group rats than in the MTX/S (171.3±16, 218. ±15 and 114.8±3, respectively). Histopathology showed that simvastatin reduced significantly (p<0.05) the damage induced by methotrexate in the mucosa of the esophagus, stomach, jejunum and colon. Conclusion: Simvastatin showed anti-inflammatory action in rats, suggesting potential clinical implication in the prevention or attenuation of mucositis induced by methotrexate.