Protective effects of sigma 1 receptor agonist PRE084 on 2,4,6-trinitrobenzene sulfonic acid–induced experimental colitis in mice
10.4174/astr.2022.103.3.160
- Author:
Hyun Il SEO
1
;
Seong Chun KWON
;
Jae Young KWAK
Author Information
1. Department of Internal Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Korea
- Publication Type:ORIGINAL ARTICLE
- From:Annals of Surgical Treatment and Research
2022;103(3):160-168
- CountryRepublic of Korea
- Language:English
-
Abstract:
Purpose:We aimed to investigate the protective effect of sigma 1 receptor agonist and antagonist, PRE084 and BD1047, respectively, on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice.
Methods:Thirty male ICR mice were randomly divided into 5 groups: control, 50% ethanol, colitis, PRE084 + colitis, and combined (PRE084 + BD1047 + colitis). Colitis was induced by intrarectal administration of TNBS. PRE084 and BD1047 were injected daily, starting 3 days before colitis induction. Distal colon tissue was excised for histopathological evaluation, and levels of glutathione (GSH), superoxide dismutase (SOD), myeloperoxidase (MPO), and lipid peroxidation were determined.
Results:Colitis caused weight loss, mucosal damage, upregulation of tumor necrosis factor-α, interleukin (IL)-1β, IL-6, MPO, and thiobarbituric acid reactive substance activities, and downregulation of GSH and SOD activities. These changes caused by TNBS-induced colitis were significantly ameliorated by PRE084 pretreatment. However, the combined pretreatment with BD1047 significantly attenuated the protective effect of PRE084, thereby reverting to the colitis-induced state.
Conclusion:We conclude that the sigma 1 receptor agonist PRE084 exhibits significant protective effects against TNBSinduced colitis, which appears to be at least partly mediated by the inhibition of inflammation and oxidative stress, and enhancement of antioxidant properties. Collectively, these results suggest that PRE084 might be an effective drug for the treatment of ulcerative colitis.
