Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 7, 2017; 23(25): 4559-4568
Published online Jul 7, 2017. doi: 10.3748/wjg.v23.i25.4559
Anti-inflammatory and anti-apoptotic effects of rosuvastatin by regulation of oxidative stress in a dextran sulfate sodium-induced colitis model
Seung Kak Shin, Jae Hee Cho, Eui Joo Kim, Eun-Kyung Kim, Dong Kyun Park, Kwang An Kwon, Jun-Won Chung, Kyoung Oh Kim, Yoon Jae Kim
Seung Kak Shin, Jae Hee Cho, Eui Joo Kim, Eun-Kyung Kim, Dong Kyun Park, Kwang An Kwon, Jun-Won Chung, Kyoung Oh Kim, Yoon Jae Kim, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon 21565, South Korea
Author contributions: Shin SK wrote the manuscript; Cho JH contributed to the analysis and interpretation of data; Shin SK and Cho JH contributed equally to this study; Kim YJ contributed to the concept and design of the study; Kim EJ and Kim EK performed the experiments; Kwon KA, Chung JW and Kim KO critically reviewed and approved the final draft; Park DK supervised the study.
Supported by Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Science, ICT and Future Planning, No. 2014R1A1A1A05008202.
Institutional review board statement: The protocol was approved by the Committee for Ethics in the Center of Animal Care and Use facility of the Gachon University Lee Gil Ya Cancer and Diabetes Institute.
Institutional animal care and use committee statement: The experimental protocol was approved by the Committee for Ethics in the Center of Animal Care and Use facility of the Gachon University Lee Gil Ya Cancer and Diabetes Institute. (LCDI-2015-0044).
Conflict-of-interest statement: The authors declare no conflict of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Yoon Jae Kim, MD, PhD, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Gachon University Gil Medical Center, 21, Namdong-daero 774 beon-gil, Namdong-gu, Incheon 21565, South Korea. yoonmed@gachon.ac.kr
Telephone: +82-32-4603778 Fax: +82-32-4603408
Received: March 11, 2017
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
Abstract
AIM

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.

METHODS

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.

RESULTS

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).

CONCLUSION

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.

Keywords: Oxidative stress; Inflammatory bowel disease; Rosuvastatin; Apoptosis

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.