Sodium Selenite Modulates Ido1/ Kynurenine, Tlr4, Nf-Κb and Bcl2/Bax Pathway and Mitigates Acetic Acid- Induced Colitis in Rat Publisher Pubmed



Ala M^{1, 2} ; Jafari RM¹ ; Nematian H^{1, 2} ; Shadboorestan A³ ; Dehpour AR^{1, 2} Show Affiliations
Source: Cellular Physiology and Biochemistry Published:2022

Abstract

Background/Aims: Colitis is a main presentation of inflammatory bowel disease (IBD) and yet, has no definitive cure. Currently, corticosteroids, anti-tumor necrosis factor (anti-TNF) agents and 5-aminosalicylic acid derivatives are prescribed for management of colitis. Except their failure rate, they are not always tolerated because of their severe adverse effects. Additive formulas with fewer adverse effects may improve the treatment of colitis. Methods: In this study, colitis was induced with intra-rectal injection of three concentrations of acetic acid (4, 6 and 8 v/v). Each group received sodium selenite (0.5 mg/kg) or saline, gavaged on days 0 and 1 for treatment. Two days after induction of colitis, rats were sacrificed and the end part of their colons were resected for macroscopic and microscopic evaluation and molecular measurement. Results: Sodium selenite improved macroscopic and microscopic view of the colon, decreased cryptitis, crypt abscess and inflammatory cells infiltration and partly maintained mucosal structure. Sodium selenite markedly reduced tissue levels of malondialdehyde (MDA), TNF-α and interferon γ (INF-γ) and decreased myeloperoxidase (MPO) activity. Treatment with sodium selenite also significantly downregulated IL17, IL22, indoleamine 2,3-dioxygenase (IDO1), and kynurenine levels. Western blotting revealed that sodium selenite prevented apoptosis by increasing bcl2/Bax ratio. Furthermore, our findings showed that sodium selenite significantly downregulated the upstream inflammatory molecules such as nuclear factor kappa B (NF-κB) and toll-like receptor 4 (TLR4) in colitis. Conclusion: These findings show that sodium selenite alleviates inflammatory response and oxidative stress and protects against colitis. © 2022 The Author(s).