Risperidone attenuates acetic acid-induced colitis in rats through inhibition of TLR4/NF-kB signaling pathway.,Immunopharmacology and Immunotoxicology

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Risperidone attenuates acetic acid-induced colitis in rats through inhibition of TLR4/NF-kB signaling pathway.
Immunopharmacology and Immunotoxicology ( IF 2.9 ) Pub Date : 2020-08-25 , DOI: 10.1080/08923973.2020.1808987
Hasan Yousefi-Manesh _{1,

2} , Pegah Dejban _{1,

2} , Faiza Mumtaz _{1,

2} , Alireza Abdollahi ₃ , Mohsen Chamanara ₄ , Ahmadreza Dehpour _{1,

2} , Amin Hasanvand ₅ , Amir Rashidian _{1,

2}

Affiliation

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.

中文翻译：

利培酮通过抑制TLR4 / NF-kB信号传导途径减轻大鼠乙酸诱发的结肠炎。

目标

本研究的目的是通过抑制TLR4 / NF-kB途径探索利培酮在乙酸诱发的大鼠结肠炎中的抗炎潜力。

方法

急性结肠炎的诱导是通过直肠内施用2 mL 4％的稀乙酸溶液进行的。在诱发结肠炎后两小时，连续五天向wistar大鼠口服地塞米松（2 mg / kg）作为标准的药物哌啶酮（2、4和6 mg / kg）。最后一次治疗后24小时，通过颈脱位法处死动物。进行了宏观和微观损伤评估。用生化和ELISA方法分别评估髓过氧化物酶（MPO）酶活性和肿瘤坏死因子-α（TNF-α）水平。此外，进行了免疫组织化学（IHC）来检测TLR4和pNF-kB蛋白的表达。

结果

地塞米松（2 mg / kg）或利培酮（2、4和6 mg / kg）改善了乙酸诱导的宏观病变（p <.001）和微观病变。此外，与醋酸组相比，利培酮（2、4和6 mg / kg）抑制结肠组织中MPO和TNF-α的活性（p <.01，p <.001）。此外，地塞米松和利培酮（2、4和6 mg / kg）均显着降低了乙酸诱导的TLR4和pNF-kB蛋白的表达（p <.05 ，p <.01 ，p <.001）。