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Antifibrotic Effects of the Dual CCR2/CCR5 Antagonist Cenicriviroc in Animal Models of Liver and Kidney Fibrosis

Lefebvre, Eric ; Moyle, Graeme ; Reshef, Ran ; Richman, Lee ; Thompson, Melanie ; Feng, Hong ; Chou, Hsin-L ; Hashiguchi, Taishi ; Plato, Craig ; Poulin, Dominic ; Richards, Toni ; Yoneyama, Hiroyuki ; Jenkins, Helen ; Friedman, Scott

PLoS One, Jun 2016, Vol.11(6), p.e0158156 [Peer Reviewed Journal]

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  • Title:
    Antifibrotic Effects of the Dual CCR2/CCR5 Antagonist Cenicriviroc in Animal Models of Liver and Kidney Fibrosis
  • Author: Lefebvre, Eric ; Moyle, Graeme ; Reshef, Ran ; Richman, Lee ; Thompson, Melanie ; Feng, Hong ; Chou, Hsin-L ; Hashiguchi, Taishi ; Plato, Craig ; Poulin, Dominic ; Richards, Toni ; Yoneyama, Hiroyuki ; Jenkins, Helen ; Friedman, Scott
  • Description: Background & Aims Interactions between C-C chemokine receptor types 2 (CCR2) and 5 (CCR5) and their ligands, including CCL2 and CCL5, mediate fibrogenesis by promoting monocyte/macrophage recruitment and tissue infiltration, as well as hepatic stellate cell activation. Cenicriviroc (CVC) is an oral, dual CCR2/CCR5 antagonist with nanomolar potency against both receptors. CVC’s anti-inflammatory and antifibrotic effects were evaluated in a range of preclinical models of inflammation and fibrosis. Methods Monocyte/macrophage recruitment was assessed in vivo in a mouse model of thioglycollate-induced peritonitis. CCL2-induced chemotaxis was evaluated ex vivo on mouse monocytes. CVC’s antifibrotic effects were evaluated in a thioacetamide-induced rat model of liver fibrosis and mouse models of diet-induced non-alcoholic steatohepatitis (NASH) and renal fibrosis. Study assessments included body and liver/kidney weight, liver function test, liver/kidney morphology and collagen deposition, fibrogenic...
  • Is Part Of: PLoS One, Jun 2016, Vol.11(6), p.e0158156
  • Identifier: E-ISSN: 19326203 ; DOI: 10.1371/journal.pone.0158156
  • Subjects: United States–Us ; South San Francisco California ; Japan ; Montreal Quebec Canada ; Atlanta Georgia ; New York ; Chemotaxis ; Liver ; Receptors ; Carbon-Carbon Composites ; Gastroenterology ; Cc Chemokine Receptors ; Fatty Liver ; Cytokines ; Liver Diseases ; Animal Models ; In Vivo Methods and Tests ; Ccr2 Protein ; Rodents
  • Language: English
  • Source: © ProQuest LLC All rights reserved
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