Atorvastatin attenuates TNBS-induced rat colitis: the involvement of the TLR4/NF-kB signaling pathway

• Published in: Inflammopharmacology 2016-06, Vol.24 (2-3), p.109-118
• Main Authors: Rashidian, Amir, Muhammadnejad, Ahad, Dehpour, Ahmad-Reza, Mehr, Shahram Ejtemai, Akhavan, Maziar Mohammad, Shirkoohi, Reza, Chamanara, Mohsen, Mousavi, Seyyedeh-Elaheh, Rezayat, Seyed-Mahdi
• Format: Article
• Language: English
• Subjects: Allergology; Animals; Atorvastatin Calcium - therapeutic use; Biomedical and Life Sciences; Biomedicine; Colitis - chemically induced; Colitis - drug therapy; Colitis - metabolism; Dermatology; Gastroenterology; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Immunology; Male; NF-kappa B - antagonists & inhibitors; NF-kappa B - biosynthesis; Original Article; Pharmacology/Toxicology; Random Allocation; Rats; Rats, Wistar; Rheumatology; Signal Transduction - drug effects; Signal Transduction - physiology; Toll-Like Receptor 4 - antagonists & inhibitors; Toll-Like Receptor 4 - biosynthesis; Trinitrobenzenesulfonic Acid - toxicity
• ISSN: 0925-4692; 1568-5608
• DOI: 10.1007/s10787-016-0263-6

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.