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

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...

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Bibliographic Details
Published in:Inflammopharmacology 2018-04, Vol.26 (2), p.599-609
Main Authors: França, Maria Eduarda Rocha de, Rocha, Sura Wanessa Santos, Oliveira, Wilma Helena, Santos, Laise Aline, de Oliveira, Anne Gabrielle Vasconcelos, Barbosa, Karla Patrícia Sousa, Nunes, Ana Karolina Santana, Rodrigues, Gabriel Barros, Lós, Deniele Bezerra, Peixoto, Christina Alves
Format: Article
Language:English
Subjects:
Allergology
Biomedical and Life Sciences
Biomedicine
Dermatology
Gastroenterology
Immunology
Original Article
Pharmacology/Toxicology
Rheumatology
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Summary: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 (CCl 4 ) 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 CCl 4 -induced liver injury and the progression of liver fibrosis, exerting a potential fibrolytic effect in the CCl 4 -induced fibrosis model.
ISSN:0925-4692
1568-5608
DOI:10.1007/s10787-017-0329-0