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13.04.2017 | Original Article

Diethylcarbamazine attenuates the expression of pro-fibrogenic markers and hepatic stellate cells activation in carbon tetrachloride-induced liver fibrosis

verfasst von: Maria Eduarda Rocha de França, Sura Wanessa Santos Rocha, Wilma Helena Oliveira, Laise Aline Santos, Anne Gabrielle Vasconcelos de Oliveira, Karla Patrícia Sousa Barbosa, Ana Karolina Santana Nunes, Gabriel Barros Rodrigues, Deniele Bezerra Lós, Christina Alves Peixoto

Erschienen in: Inflammopharmacology | Ausgabe 2/2018

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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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Titel: Diethylcarbamazine attenuates the expression of pro-fibrogenic markers and hepatic stellate cells activation in carbon tetrachloride-induced liver fibrosis
verfasst von: Maria Eduarda Rocha de França
Sura Wanessa Santos Rocha
Wilma Helena Oliveira
Laise Aline Santos
Anne Gabrielle Vasconcelos de Oliveira
Karla Patrícia Sousa Barbosa
Ana Karolina Santana Nunes
Gabriel Barros Rodrigues
Deniele Bezerra Lós
Christina Alves Peixoto
Publikationsdatum: 13.04.2017
Verlag: Springer International Publishing
Erschienen in: Inflammopharmacology / Ausgabe 2/2018
Print ISSN: 0925-4692
Elektronische ISSN: 1568-5608
DOI: https://doi.org/10.1007/s10787-017-0329-0

Springer Medizin

Abstract

Background and aim

Methods

Results

Conclusions

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