Anti-inflammatory effects of simvastatin in nonsteroidal anti-inflammatory drugs-induced small bowel injury.
نویسندگان
چکیده
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 α (TNF-α) 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-α-stimulated IEC-6 cells. Treatment with a combination of 50 ng/ml TNF-α and μM simvastatin decreased activation of Akt, IκBα, and nuclear factor-κB p65 level in IEC-6 cells. By DCF-DA staining, intracellular reactive oxygen species (ROS) production was increased in TNF-α-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.
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ورودعنوان ژورنال:
- Journal of physiology and pharmacology : an official journal of the Polish Physiological Society
دوره 68 1 شماره
صفحات -
تاریخ انتشار 2017