Amir Rashidian1, Ahad Muhammadnejad2, Ahmad-Reza Dehpour1, Shahram Ejtemai Mehr1, Maziar Mohammad Akhavan3, Reza Shirkoohi2, Mohsen Chamanara1, Seyyedeh-Elaheh Mousavi1,4, Seyed-Mahdi Rezayat5,6. 1. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, 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. 5. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran. mhdirezayat43@gmail.com. 6. Department of Toxicology and Pharmacology, School of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University (IAUPS), Tehran, Iran. mhdirezayat43@gmail.com.
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.
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 ratcolitis. 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 ratcolitis may involve the inhibition of the TLR4/NFkB signaling pathway.
Authors: Makoto Sasaki; Sulaiman Bharwani; Paul Jordan; Takashi Joh; Kenneth Manas; April Warren; Hirohisa Harada; Patsy Carter; John W Elrod; Michael Wolcott; Matthew B Grisham; J Steven Alexander Journal: J Pharmacol Exp Ther Date: 2003-04 Impact factor: 4.030