Risperidone attenuates acetic acid-induced colitis in rats through inhibition of TLR4/NF-kB signaling pathway

Yousefi-Manesh, Hasan and Hasanvand, Amin and Dejban, Pegah and Mumtaz, Faiza (2020) Risperidone attenuates acetic acid-induced colitis in rats through inhibition of TLR4/NF-kB signaling pathway. Immunopharmacology and Immunotoxicology.

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Aim The purpose of the present study is to explore the anti-inflammatory potential of risperidone in acetic acid-induced rat colitis through inhibition of TLR4/NF-kB pathway Methods Acute colitis induction was done by intra-rectal administration of 2 mL of 4% diluted acetic acid solution. Two h after colitis induction, dexamethasone (2 mg/kg) as standard drugorrisperidone (2, 4 and 6 mg/kg) were administered orally to wistar rats for five consecutive days. 24 h after the last treatment, animals were sacrificed by cervical dislocation. Macroscopic and microscopic damage evaluation was done. Biochemical and ELISA methods were used to assess myeloid peroxidase (MPO) enzyme activity and tumor necrosis factor-α (TNF-α) level respectively. Moreover,immunohistochemistry (IHC) was performed to detect the expression of TLR4 and pNF-kBproteins. Results Dexamethasone (2mg/kg)orrisperidone(2, 4 and 6 mg/kg) improved acetic acid-induced macroscopic (P < 0.001) and microscopic lesions.Additionally, risperidone (2, 4 and 6 mg/kg)inhibited the activity of MPO and TNF-α (P < 0.01, P < 0.001) in the colon tissue compared to acetic acid group. Furthermore, bothdexamethasone and risperidone(2, 4 and 6 mg/kg) significantly reducedacetic acid-induced expression of TLR4and pNF-kB proteins (p < 0.05, p < 0.01, P < 0.001). Conclusion The anti-inflammatory effect of risperidoneon acetic acid-induced colitis in rats may involve inhibition of TLR4 and NF-kB signaling pathway.

Item Type: Article
Subjects: R Medicine > RB Pathology
Divisions: Faculty of Medicine, Health and Life Sciences > School of Medicine
Depositing User: samira sepahvandy
Date Deposited: 22 Aug 2020 03:31
Last Modified: 22 Aug 2020 03:31
URI: http://eprints.lums.ac.ir/id/eprint/2286

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