Skip to main content
Erschienen in: Inflammopharmacology 2-3/2016

02.04.2016 | Original Article

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

verfasst von: Amir Rashidian, Ahad Muhammadnejad, Ahmad-Reza Dehpour, Shahram Ejtemai Mehr, Maziar Mohammad Akhavan, Reza Shirkoohi, Mohsen Chamanara, Seyyedeh-Elaheh Mousavi, Seyed-Mahdi Rezayat

Erschienen in: Inflammopharmacology | Ausgabe 2-3/2016

Einloggen, um Zugang zu erhalten

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.
Literatur
Zurück zum Zitat Aderem A (2001) Role of toll-like receptors in inflammatory response in macrophages. Crit Care Med 29:S16–S18CrossRefPubMed Aderem A (2001) Role of toll-like receptors in inflammatory response in macrophages. Crit Care Med 29:S16–S18CrossRefPubMed
Zurück zum Zitat Aderem A, Ulevitch RJ (2000) Toll-like receptors in the induction of the innate immune response. Nature 406:782–787CrossRefPubMed Aderem A, Ulevitch RJ (2000) Toll-like receptors in the induction of the innate immune response. Nature 406:782–787CrossRefPubMed
Zurück zum Zitat Aktunc E, Kayhan B, Arasli M, Gun BD, Barut F (2011) The effect of atorvastatin and its role on systemic cytokine network in treatment of acute experimental colitis. Immunopharmacol Immunotoxicol 33:667–675CrossRefPubMed Aktunc E, Kayhan B, Arasli M, Gun BD, Barut F (2011) The effect of atorvastatin and its role on systemic cytokine network in treatment of acute experimental colitis. Immunopharmacol Immunotoxicol 33:667–675CrossRefPubMed
Zurück zum Zitat Allred D, Harvey JM, Berardo M, Clark GM (1998) Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Modern Pathol Off J US Can Acad Pathol Inc 11:155–168 Allred D, Harvey JM, Berardo M, Clark GM (1998) Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Modern Pathol Off J US Can Acad Pathol Inc 11:155–168
Zurück zum Zitat Brubaker SW, Bonham KS, Zanoni I, Kagan JC (2015) Innate immune pattern recognition: a cell biological perspective. Annu Rev Immunol 33:257–290CrossRefPubMed Brubaker SW, Bonham KS, Zanoni I, Kagan JC (2015) Innate immune pattern recognition: a cell biological perspective. Annu Rev Immunol 33:257–290CrossRefPubMed
Zurück zum Zitat Deshmukh C, Veeresh B, Pawar A (2010) Protective effect of emblica officinalis fruit extract on acetic acid induced colitis in rats. J Herbal Med Toxicol 4:83–87 Deshmukh C, Veeresh B, Pawar A (2010) Protective effect of emblica officinalis fruit extract on acetic acid induced colitis in rats. J Herbal Med Toxicol 4:83–87
Zurück zum Zitat Dhamija P, Hota D, Kochhar R, Sachdev A, Chakrabarti A (2014) Randomized clinical trial: atorvastatin versus placebo in patients with acute exacerbation of mild to moderate ulcerative colitis. Indian J Gastroenterol 33:151–156CrossRefPubMed Dhamija P, Hota D, Kochhar R, Sachdev A, Chakrabarti A (2014) Randomized clinical trial: atorvastatin versus placebo in patients with acute exacerbation of mild to moderate ulcerative colitis. Indian J Gastroenterol 33:151–156CrossRefPubMed
Zurück zum Zitat Didierlaurent A, Sirard JC, Kraehenbuhl JP, Neutra MR (2002) How the gut senses its content. Cell Microbiol 4:61–72CrossRefPubMed Didierlaurent A, Sirard JC, Kraehenbuhl JP, Neutra MR (2002) How the gut senses its content. Cell Microbiol 4:61–72CrossRefPubMed
Zurück zum Zitat Janeway CA Jr, Medzhitov R (2002) Innate immune recognition. Ann Rev Immunol 20:197–216CrossRef Janeway CA Jr, Medzhitov R (2002) Innate immune recognition. Ann Rev Immunol 20:197–216CrossRef
Zurück zum Zitat Ke X et al (2013) Qing hua chang yin exerts therapeutic effects against ulcerative colitis through the inhibition of the tlr4/nf-κb pathway. Int J Mol Med 32:926–930PubMed Ke X et al (2013) Qing hua chang yin exerts therapeutic effects against ulcerative colitis through the inhibition of the tlr4/nf-κb pathway. Int J Mol Med 32:926–930PubMed
Zurück zum Zitat Khan I, Oriowo MA, Anim JT (2005) Amelioration of experimental colitis by na-h exchanger-1 inhibitor amiloride is associated with reversal of il-1β and erk mitogen-activated protein kinase. Scand J Gastroenterol 40:578–585CrossRefPubMed Khan I, Oriowo MA, Anim JT (2005) Amelioration of experimental colitis by na-h exchanger-1 inhibitor amiloride is associated with reversal of il-1β and erk mitogen-activated protein kinase. Scand J Gastroenterol 40:578–585CrossRefPubMed
Zurück zum Zitat Kojouharoff G, Hans W, Obermeier F, Andus T, Gross V, Falk W (1997) Neutralization of tumour necrosis factor (tnf) but not of il-1 reduces inflammation in chronic dextran sulphate sodium-induced colitis in mice. Clin Exp Immunol 107:353–358CrossRefPubMedPubMedCentral Kojouharoff G, Hans W, Obermeier F, Andus T, Gross V, Falk W (1997) Neutralization of tumour necrosis factor (tnf) but not of il-1 reduces inflammation in chronic dextran sulphate sodium-induced colitis in mice. Clin Exp Immunol 107:353–358CrossRefPubMedPubMedCentral
Zurück zum Zitat Lee JY, Kim JS, Kim JM, Kim N, Jung HC, Song IS (2007) Simvastatin inhibits nf-κb signaling in intestinal epithelial cells and ameliorates acute murine colitis. Int Immunopharmacol 7:241–248CrossRefPubMed Lee JY, Kim JS, Kim JM, Kim N, Jung HC, Song IS (2007) Simvastatin inhibits nf-κb signaling in intestinal epithelial cells and ameliorates acute murine colitis. Int Immunopharmacol 7:241–248CrossRefPubMed
Zurück zum Zitat Lin S et al (2012) Heme activates tlr4-mediated inflammatory injury via myd88/trif signaling pathway in intracerebral hemorrhage. J Neuroinflammation 9:46CrossRefPubMedPubMedCentral Lin S et al (2012) Heme activates tlr4-mediated inflammatory injury via myd88/trif signaling pathway in intracerebral hemorrhage. J Neuroinflammation 9:46CrossRefPubMedPubMedCentral
Zurück zum Zitat Maron DJ, Fazio S, Linton MF (2000) Current perspectives on statins. Circulation 101:207–213CrossRefPubMed Maron DJ, Fazio S, Linton MF (2000) Current perspectives on statins. Circulation 101:207–213CrossRefPubMed
Zurück zum Zitat Molodecky NA et al (2012) Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology 142(46–54):e42PubMed Molodecky NA et al (2012) Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology 142(46–54):e42PubMed
Zurück zum Zitat Morris GP, Beck PL, Herridge MS, Depew WT, Szewczuk MR, Wallace JL (1989) Hapten-induced model of chronic inflammation and ulceration in the rat colon. Gastroenterology 96:795–803PubMed Morris GP, Beck PL, Herridge MS, Depew WT, Szewczuk MR, Wallace JL (1989) Hapten-induced model of chronic inflammation and ulceration in the rat colon. Gastroenterology 96:795–803PubMed
Zurück zum Zitat Mukhopadhya A, Gilmour H, Plevris J (2008) Pravastatin-induced colitis. Eur J Gastroenterol Hepatol 20:810–812CrossRefPubMed Mukhopadhya A, Gilmour H, Plevris J (2008) Pravastatin-induced colitis. Eur J Gastroenterol Hepatol 20:810–812CrossRefPubMed
Zurück zum Zitat Naito Y et al (2006) Rosuvastatin, a new hmg-coa reductase inhibitor, reduces the colonic inflammatory response in dextran sulfate sodium-induced colitis in mice. Int J Mol Med 17:997–1004PubMed Naito Y et al (2006) Rosuvastatin, a new hmg-coa reductase inhibitor, reduces the colonic inflammatory response in dextran sulfate sodium-induced colitis in mice. Int J Mol Med 17:997–1004PubMed
Zurück zum Zitat Ohkawara T et al (2006) Regulation of toll-like receptor 4 expression in mouse colon by macrophage migration inhibitory factor. Histochem Cell Biol 125:575–582CrossRefPubMed Ohkawara T et al (2006) Regulation of toll-like receptor 4 expression in mouse colon by macrophage migration inhibitory factor. Histochem Cell Biol 125:575–582CrossRefPubMed
Zurück zum Zitat Pålsson-McDermott EM, O’Neill LA (2004) Signal transduction by the lipopolysaccharide receptor, toll-like receptor-4. Immunology 113:153–162CrossRefPubMedPubMedCentral Pålsson-McDermott EM, O’Neill LA (2004) Signal transduction by the lipopolysaccharide receptor, toll-like receptor-4. Immunology 113:153–162CrossRefPubMedPubMedCentral
Zurück zum Zitat Rashidian A, Roohi P, Mehrzadi S, Ghannadi AR, Minaiyan M (2015) Protective effect of ocimum basilicum essential oil against acetic acid–induced colitis in rats. J Evid Based Complement Altern Med 2156587215616550 Rashidian A, Roohi P, Mehrzadi S, Ghannadi AR, Minaiyan M (2015) Protective effect of ocimum basilicum essential oil against acetic acid–induced colitis in rats. J Evid Based Complement Altern Med 2156587215616550
Zurück zum Zitat Rutgeerts P (1999) Review article: efficacy of infliximab in crohn’s disease—induction and maintenance of remission. Aliment Pharmacol Ther 13:9–15CrossRefPubMed Rutgeerts P (1999) Review article: efficacy of infliximab in crohn’s disease—induction and maintenance of remission. Aliment Pharmacol Ther 13:9–15CrossRefPubMed
Zurück zum Zitat Sasaki M et al (2003) The 3-hydroxy-3-methylglutaryl-coa reductase inhibitor pravastatin reduces disease activity and inflammation in dextran-sulfate induced colitis. J Pharmacol Exp Ther 305:78–85CrossRefPubMed Sasaki M et al (2003) The 3-hydroxy-3-methylglutaryl-coa reductase inhibitor pravastatin reduces disease activity and inflammation in dextran-sulfate induced colitis. J Pharmacol Exp Ther 305:78–85CrossRefPubMed
Zurück zum Zitat Scheiffele F,Fuss IJ (2002) Induction of tnbs colitis in mice Curr Protoc immunol 15.19. 11–15.19. 14 Scheiffele F,Fuss IJ (2002) Induction of tnbs colitis in mice Curr Protoc immunol 15.19. 11–15.19. 14
Zurück zum Zitat Szebeni B et al (2008) Increased expression of toll-like receptor (tlr) 2 and tlr4 in the colonic mucosa of children with inflammatory bowel disease. Clin Exp Immunol 151:34–41CrossRefPubMedPubMedCentral Szebeni B et al (2008) Increased expression of toll-like receptor (tlr) 2 and tlr4 in the colonic mucosa of children with inflammatory bowel disease. Clin Exp Immunol 151:34–41CrossRefPubMedPubMedCentral
Zurück zum Zitat Tan J, Pretorius CF, Flanagan PV, Pais A (2012) Adverse drug reaction: rosuvastatin as a cause for ischaemic colitis in a 64-year-old woman. BMJ Case Reports 2012:bcr1120115270 Tan J, Pretorius CF, Flanagan PV, Pais A (2012) Adverse drug reaction: rosuvastatin as a cause for ischaemic colitis in a 64-year-old woman. BMJ Case Reports 2012:bcr1120115270
Zurück zum Zitat Teng X, Xu L-F, Zhou P, Sun H-W, Sun M (2009) Effects of trefoil peptide 3 on expression of tnf-α, tlr4, and nf-κb in trinitrobenzene sulphonic acid induced colitis mice. Inflammation 32:120–129CrossRefPubMed Teng X, Xu L-F, Zhou P, Sun H-W, Sun M (2009) Effects of trefoil peptide 3 on expression of tnf-α, tlr4, and nf-κb in trinitrobenzene sulphonic acid induced colitis mice. Inflammation 32:120–129CrossRefPubMed
Zurück zum Zitat Ungaro R et al (2009) A novel toll-like receptor 4 antagonist antibody ameliorates inflammation but impairs mucosal healing in murine colitis. Am J Physiol Gastrointest Liver Physiol 296:G1167–G1179CrossRefPubMedPubMedCentral Ungaro R et al (2009) A novel toll-like receptor 4 antagonist antibody ameliorates inflammation but impairs mucosal healing in murine colitis. Am J Physiol Gastrointest Liver Physiol 296:G1167–G1179CrossRefPubMedPubMedCentral
Zurück zum Zitat Wang K, Wan YJY (2008) Nuclear receptors and inflammatory diseases. Exp Biol Med 233:496–506CrossRef Wang K, Wan YJY (2008) Nuclear receptors and inflammatory diseases. Exp Biol Med 233:496–506CrossRef
Zurück zum Zitat Wierzbicki AS, Poston R, Ferro A (2003) The lipid and non-lipid effects of statins. Pharmacol Therap 99:95–112CrossRef Wierzbicki AS, Poston R, Ferro A (2003) The lipid and non-lipid effects of statins. Pharmacol Therap 99:95–112CrossRef
Zurück zum Zitat Zeng Z, Zhan L, Liao H, Chen L, Lv X (2013) Curcumin improves tnbs-induced colitis in rats by inhibiting il-27 expression via the tlr4/nf-κb signaling pathway. Planta Med 79:102–109PubMed Zeng Z, Zhan L, Liao H, Chen L, Lv X (2013) Curcumin improves tnbs-induced colitis in rats by inhibiting il-27 expression via the tlr4/nf-κb signaling pathway. Planta Med 79:102–109PubMed
Metadaten
Titel
Atorvastatin attenuates TNBS-induced rat colitis: the involvement of the TLR4/NF-kB signaling pathway
verfasst von
Amir Rashidian
Ahad Muhammadnejad
Ahmad-Reza Dehpour
Shahram Ejtemai Mehr
Maziar Mohammad Akhavan
Reza Shirkoohi
Mohsen Chamanara
Seyyedeh-Elaheh Mousavi
Seyed-Mahdi Rezayat
Publikationsdatum
02.04.2016
Verlag
Springer International Publishing
Erschienen in
Inflammopharmacology / Ausgabe 2-3/2016
Print ISSN: 0925-4692
Elektronische ISSN: 1568-5608
DOI
https://doi.org/10.1007/s10787-016-0263-6

Weitere Artikel der Ausgabe 2-3/2016

Inflammopharmacology 2-3/2016 Zur Ausgabe