Risperidone Attenuates Acetic Acid-Induced Colitis in Rats Through Inhibition of Tlr4/Nf-Kb Signaling Pathway Publisher Pubmed



Yousefimanesh H^{1, 2} ; Dejban P^{1, 2} ; Mumtaz F^{1, 2} ; Abdollahi A³ ; Chamanara M⁴ ; Dehpour A^{1, 2} ; Hasanvand A⁵ ; Rashidian A^{1, 2}
Source: Immunopharmacology and Immunotoxicology Published:2020

Abstract

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 (2 mg/kg) or risperidone (2, 4 and 6 mg/kg) improved acetic acid-induced macroscopic (p '.001) and microscopic lesions. Additionally, risperidone (2, 4 and 6 mg/kg) inhibited the activity of MPO and TNF-α (p '.01, p '.001) in the colon tissue compared to acetic acid group. Furthermore, bothdexamethasone and risperidone (2, 4 and 6 mg/kg) significantly reduced acetic acid-induced expression of TLR4and pNF-kB proteins (p '.05, p '.01, p '.001). Conclusion: The anti-inflammatory effect of risperidone on acetic acid-induced colitis in rats may involve inhibition of TLR4 and NF-kB signaling pathway. © 2020 Informa UK Limited, trading as Taylor & Francis Group.