Abstract
Background and aim
While diethylcarbamazine citrate (DEC) displays important anti-inflammatory effects in experimental models of liver injury, the mechanisms of its action remain poorly understood. The aim of the present study was to investigate the fibrolytic potential of DEC.
Methods
Mice receive two injections of carbon tetrachloride (CCl4) per week for 8 weeks. DEC 50 mg/kg body weight was administered through drinking water during the last 12 days of liver injury.
Results
The expression of hepatic stellate cells (HSCs) activation markers, including smooth muscle α-actin (α-SMA), collagen I, transforming growth factor-β 1 (TGF-β1), matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-1 (TIMP-1) was assessed. The influence of DEC on the intracellular MAPK pathways of the HSCs (JNK and p38 MAPK) was also estimated. DEC inhibited HSCs activation measured as the production of α-SMA and collagen I. In addition, it down regulated the production of TGF-β1 and TIMP-1, and concomitantly increased MMP-2 activity. Furthermore, DEC significantly inhibited the activation of the JNK and p38 MAPK signaling pathways.
Conclusions
In conclusion, DEC significantly attenuated the severity of CCl4-induced liver injury and the progression of liver fibrosis, exerting a potential fibrolytic effect in the CCl4-induced fibrosis model.
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Acknowledgements
This study was supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Universidade Federal de Pernambuco (UFPE) and the Centro de Pesquisa Aggeu Magalhães (CPqAM/FIOCRUZ) in Recife, Brazil.
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França, M.E.R., Rocha, S.W.S., Oliveira, W.H. et al. Diethylcarbamazine attenuates the expression of pro-fibrogenic markers and hepatic stellate cells activation in carbon tetrachloride-induced liver fibrosis. Inflammopharmacol 26, 599–609 (2018). https://doi.org/10.1007/s10787-017-0329-0
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DOI: https://doi.org/10.1007/s10787-017-0329-0