ORIGINAL ARTICLE Diethylcarbamazine attenuates the expression of pro-fibrogenic markers and hepatic stellate cells activation in carbon tetrachloride-induced liver fibrosis Maria Eduarda Rocha de Franc ¸a 1,2 • Sura Wanessa Santos Rocha 1 • Wilma Helena Oliveira 1,2 • Laise Aline Santos 1 • Anne Gabrielle Vasconcelos de Oliveira 3 • Karla Patrı ´cia Sousa Barbosa 4 • Ana Karolina Santana Nunes 1 • Gabriel Barros Rodrigues 1,2 • Deniele Bezerra Lo ´s 1,5 • Christina Alves Peixoto 1 Received: 22 November 2016 / Accepted: 17 February 2017 Ó Springer International Publishing 2017 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 tetrachlo- ride (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 a-actin (a- SMA), collagen I, transforming growth factor-b 1 (TGF-b1), 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 a-SMA and collagen I. In addition, it down regulated the production of TGF-b1 and TIMP-1, and concomitantly increased MMP-2 activity. Furthermore, DEC significantly inhibited the acti- vation of the JNK and p38 MAPK signaling pathways. Conclusions In conclusion, DEC significantly attenuated the severity of CCl 4 -induced liver injury and the progres- sion of liver fibrosis, exerting a potential fibrolytic effect in the CCl 4 -induced fibrosis model. Keywords Diethylcarbamazine citrate Á Liver fibrosis Á Carbon tetrachloride (CCl 4 ) Introduction Liver fibrosis is a serious global public health problem because of its life-threatening complications, which include cirrhosis, portal hypertension and liver failure, and the risk of hepatocellular carcinoma (Iredale 2007; Lee and Friedman 2011). This disease is a wound healing response to chronic liver injury arising from different etiologies, including alcohol and drug abuse and viral, autoimmune and metabolic syndrome diseases (Cubero et al. 2009; Bosserhoff and Hellerbrand 2011; Probst et al. 2011; Xu et al. 2012). Many cell types are involved in the pathogenesis of hepatic fibrosis. In the normal liver, hepatic stellate cells (HSCs) reside in the space of Disse between hepatocytes and sinusoidal endothelial cells (Friedman 2008a). Following liver injury, a variety of factors such as cytokines, chemokines or reactive oxygen species (ROS) induce the activation of HSCs, which have a crucial role in liver fibrosis (Kong et al. 2012). TGF-b1 is & Maria Eduarda Rocha de Franc ¸a mariaeduarda.rfranca@gmail.com & Christina Alves Peixoto mariaeduarda.rfranca@gmail.com; peixoto.christina@gmail.com 1 Laborato ´rio de Ultraestrutura, Centro de Pesquisa Aggeu Magalha ˜es (CPqAM/FIOCRUZ), Recife, PE, Brazil 2 Programa de Po ´s-graduac ¸a ˜o em Cie ˆncias Biolo ´gicas, Centro de Biocie ˆncias, Universidade Federal de Pernambuco (UFPE), Recife, PE, Brazil 3 Laborato ´rio de Biologia celular e Ultraestrutura, Centro de Tecnologias Estrate ´gicas do Nordeste (CETENE), Recife, PE, Brazil 4 Universidade Federal de Pernambuco (UFPE), Campus Vito ´ria de Santo Anta ˜o, PE, Brazil 5 Programa de Po ´s-graduac ¸a ˜o em Biotecnologia/RENORBIO, Universidade Federal de Pernambuco, Recife, PE, Brazil Inflammopharmacol DOI 10.1007/s10787-017-0329-0 Inflammopharmacology 123