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

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.

Keywords:

• Acetic acid
• pNF-kB
• risperidone
• TLR4
• ulcerative colitis

Disclosure statement

We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome.

Author contributions

AR and AD: conceptualization; roles/writing—original draft, HYM and FM: experimental procedures; methodology and formal analysis, AA: pathology and IHC analysis, PD and MC: writing the paper; AR and AH: Review and editing and supervision.

Additional information

Funding

This study was financially supported by Tehran University of Medical Sciences, Tehran, Iran [grant number 39970].