ANTI-INFLAMMATORY EFFECTS OF SIMVASTATIN IN NONSTEROIDAL ANTI-INFLAMMATORY DRUGS-INDUCED SMALL BOWEL INJURY
- Authors
- Kim, E. K.; Cho, J. H.; Jeong, A. R.; Kim, E. J.; Park, D. K.; Kwon, K. A.; Chung, J. W.; Kim, K. O.; Kim, J. H.; Kim, J. H.; Kim, Y. J.
- Issue Date
- Feb-2017
- Publisher
- POLISH PHYSIOLOGICAL SOC
- Keywords
- 3-hydroxy-3methylglutatyl-coenzyme A; reductase inhibitor; simvastatin; non-steroidal anti-inflammatory drugs; reactive oxygen species; tumor necrosis factor-a; interleukin-6; interleukin-8
- Citation
- JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY, v.68, no.1, pp.69 - 77
- Journal Title
- JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
- Volume
- 68
- Number
- 1
- Start Page
- 69
- End Page
- 77
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/6477
- ISSN
- 0867-5910
- Abstract
- Small bowel injury can occur as the result of a multifaceted process that includes increased acid secretion, generation of reactive oxygen species, and cyclooxygenase inhibition. However, no effective medication for small bowel ulceration is available. Simvastatin is an important lipid-lowering agent with anti-inflammatory activity. We aimed to validate the effects of simvastatin in vitro and in vivo. In presence or absence of simvastatin, IEC-6 small bowel cell line with 50 ng/ml of tumor nectosis factor alpha (TNF-alpha) was investigated by western blotting, qRT-PCR, and DCF-DA assay. In addition, an in vivo study of nonsteroidal anti-inflammatory drugs (NSAID)-induced small bowel inflammation was performed using 7-week-old specific-pathogen-free (SPF) male C57BL/6 mice. Simvastatin treatment reduced the mRNA levels of interleukin-6 and interleukin-8 by approximately 50% in TNF-alpha-stimulated IEC-6 cells. Treatment with a combination of 50 ng/ml TNF-alpha and 0.5 mu M simvastatin decreased activation of Akt, I kappa B alpha, and nuclear factor-kappa B p65 level in IEC-6 cells. By DCF-DA staining, intracellular reactive oxygen species (ROS) production was increased in TNF-a-stimulated cells, and treatment with simvastatin decreased the level of ROS. In addition, in vivo mouse model of NSAID-induced small bowel inflammation, the administration of simvastatin reduced the number of small bowel hemorrhagic lesions and the level of ROS production as determined by gross examination and 8-hydroxydeoxyguanosine immunohistochemistry of small bowel tissue, respectively. Simvastatin reduced NSAID-induced injuries by both suppression of ROS generation and modulation of inflammatory cytokines in vitro and in vivo. Therefore, simvastatin, an HMG-CoA reductase inhibitor, has potential as a prophylactic and therapeutic agent for NSAID-induced small bowel injury.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - 의과대학 > 의학과 > 1. Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/6477)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.