title: Atorvastatin attenuates TNBS-induced rat colitis: the involvement of the TLR4/NF-kB signaling pathway.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran.
authors.forename: Amir
authors.initials: A
authors.lastname: Rashidian
authors.affiliation: Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Ahad
authors.initials: A
authors.lastname: Muhammadnejad
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran.
authors.forename: Ahmad-Reza
authors.initials: AR
authors.lastname: Dehpour
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran.
authors.forename: Shahram Ejtemai
authors.initials: SE
authors.lastname: Mehr
authors.affiliation: Skin Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Maziar Mohammad
authors.initials: MM
authors.lastname: Akhavan
authors.affiliation: Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Shirkoohi
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Chamanara
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran.|Department of Toxicology and Pharmacology, School of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University (IAUPS), Tehran, Iran.
authors.forename: Seyyedeh-Elaheh
authors.initials: SE
authors.lastname: Mousavi
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran. mhdirezayat43@gmail.com.|Department of Toxicology and Pharmacology, School of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University (IAUPS), Tehran, Iran. mhdirezayat43@gmail.com.
authors.forename: Seyed-Mahdi
authors.initials: SM
authors.lastname: Rezayat
mesh_terms: D000818:Animals; D000069059:Atorvastatin / Q000627:therapeutic use*; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D016328:NF-kappa B; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D014302:Trinitrobenzenesulfonic Acid; D000069059:Atorvastatin
keywords: Atorvastatin; TLR4/NF-κB signaling pathway; TNBS; Ulcerative colitis