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

Inflammopharmacology. 2016 Jun;24(2-3):109-18. doi: 10.1007/s10787-016-0263-6. Epub 2016 Apr 2.

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: Atorvastatin; TLR4/NF-κB signaling pathway; TNBS; Ulcerative colitis.

MeSH terms

  • Animals
  • Atorvastatin / therapeutic use*
  • Colitis / chemically induced
  • Colitis / drug therapy*
  • Colitis / metabolism*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Male
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / biosynthesis*
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Toll-Like Receptor 4 / antagonists & inhibitors
  • Toll-Like Receptor 4 / biosynthesis*
  • Trinitrobenzenesulfonic Acid / toxicity*

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • NF-kappa B
  • Tlr4 protein, rat
  • Toll-Like Receptor 4
  • Trinitrobenzenesulfonic Acid
  • Atorvastatin