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Atorvastatin attenuates TNBS-induced rat colitis: the involvement of the TLR4/NF-kB signaling pathway
Authors:Amir Rashidian  Ahad Muhammadnejad  Ahmad-Reza Dehpour  Shahram Ejtemai Mehr  Maziar Mohammad Akhavan  Reza Shirkoohi  Mohsen Chamanara  Seyyedeh-Elaheh Mousavi  Seyed-Mahdi Rezayat
Affiliation:1.Department of Pharmacology, School of Medicine,Tehran University of Medical Sciences,Tehran,Iran;2.Cancer Research Center, Cancer Institute of Iran,Tehran University of Medical Sciences,Tehran,Iran;3.Skin Research Center,Shahid Beheshti University of Medical Sciences,Tehran,Iran;4.Department of Toxicology and Pharmacology, School of Pharmacy, Pharmaceutical Sciences Branch,Islamic Azad University (IAUPS),Tehran,Iran
Abstract:

Aim

The aim of the present study is to explore whether atorvastatin improves intestinal inflammation through the inhibition of the TLR4/NFkB signaling pathway in TNBS-induced rat colitis.

Methods

Acute colitis was induced by intra-rectal administration of 100 mg/kg TNBS dissolved in 0.25 ml of 50 % ethanol. Twenty four hours after colitis induction, saline, atorvastatin (20 and 40 mg/kg) and sulfasalazine (100 mg/kg) were given to the animals by oral route. This was repeated daily for 1 week. Body weight changes, macroscopic and microscopic lesions were assessed. MPO and TNF-α activities were detected by immunohistochemistry (IHC) and the expression level of TLR4, MyD88 and NF-κB p65 proteins were measured by western blotting analysis.

Results

Atorvastatin and sulfasalazine reduced the body weight loss, macroscopic and microscopic lesions. Additionally, both drugs decreased the expression of MPO and TNF-α positive cells in the colon tissue. Furthermore, they inhibited the TNBS-induced expression of TLR4, MyD88 and NF-κB p65 proteins.

Conclusions

It is suggested that the anti-inflammatory effect of atorvastatin on TNBS-induced rat colitis may involve the inhibition of the TLR4/NFkB signaling pathway.
Keywords:
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