Published online Jul 7, 2017. doi: 10.3748/wjg.v23.i25.4559
Peer-review started: March 15, 2017
First decision: March 30, 2017
Revised: April 4, 2017
Accepted: May 4, 2017
Article in press: May 4, 2017
Published online: July 7, 2017
Processing time: 117 Days and 23 Hours
To evaluate the anti-inflammatory and anti-apoptotic effects of rosuvastatin by regulation of oxidative stress in a dextran sulfate sodium (DSS)-induced colitis model.
An acute colitis mouse model was induced by oral administration of 5% DSS in the drinking water for 7 d. In the treated group, rosuvastatin (0.3 mg/kg per day) was administered orally before and after DSS administration for 21 d. On day 21, mice were sacrificed and the colons were removed for macroscopic examination, histology, and Western blot analysis. In the in vitro study, IEC-6 cells were stimulated with 50 ng/mL tumor necrosis factor (TNF)-α and then treated with or without rosuvastatin (2 μmol/L). The levels of reactive oxygen species (ROS), inflammatory mediators, and apoptotic markers were measured.
In DSS-induced colitis mice, rosuvastatin treatment significantly reduced the disease activity index and histological damage score compared to untreated mice (P < 0.05). Rosuvastatin also attenuated the DSS-induced increase of 8-hydroxy-2’-deoxyguanosine and NADPH oxidase-1 expression in colon tissue. Multiplex ELISA analysis revealed that rosuvastatin treatment reduced the DSS-induced increase of serum IL-2, IL-4, IL-5, IL-6, IL-12 and IL-17, and G-CSF levels. The increased levels of cleaved caspase-3, caspase-7, and poly (ADP-ribose) polymerase in the DSS group were attenuated by rosuvastatin treatment. In vitro, rosuvastatin significantly reduced the production of ROS, inflammatory mediators and apoptotic markers in TNF-α-treated IEC-6 cells (P < 0.05).
Rosuvastatin had the antioxidant, anti-inflammatory and anti-apoptotic effects in DSS-induced colitis model. Therefore, it might be a candidate anti-inflammatory drug in patients with inflammatory bowel disease.
Core tip: Oxidative stress in the intestinal tract is considered a major factor that contributes to the pathogenesis and progression of inflammatory bowel disease (IBD). We report that rosuvastatin has the antioxidant, anti-inflammatory and anti-apoptotic effects in dextran sulfate sodium (DSS)-induced colitis mice. We assume the possibility of anti-inflammatory effects of rosuvastatin through the regulation of oxidative stress, and first describe the anti-apoptotic effects of rosuvastatin in a DSS-induced colitis model. Therefore, rosuvastatin might be a candidate anti-inflammatory drug in patients with IBD.