Maria Eduarda Rocha de França1,2, Sura Wanessa Santos Rocha3, Wilma Helena Oliveira3,4, Laise Aline Santos3, Anne Gabrielle Vasconcelos de Oliveira5, Karla Patrícia Sousa Barbosa6, Ana Karolina Santana Nunes3, Gabriel Barros Rodrigues3,4, Deniele Bezerra Lós3,7, Christina Alves Peixoto1. 1. Laboratório de Ultraestrutura, Centro de Pesquisa Aggeu Magalhães (CPqAM/FIOCRUZ), Recife, PE, Brazil. mariaeduarda.rfranca@gmail.com. 2. Programa de Pós-graduação em Ciências Biológicas, Centro de Biociências, Universidade Federal de Pernambuco (UFPE), Recife, PE, Brazil. mariaeduarda.rfranca@gmail.com. 3. Laboratório de Ultraestrutura, Centro de Pesquisa Aggeu Magalhães (CPqAM/FIOCRUZ), Recife, PE, Brazil. 4. Programa de Pós-graduação em Ciências Biológicas, Centro de Biociências, Universidade Federal de Pernambuco (UFPE), Recife, PE, Brazil. 5. Laboratório de Biologia celular e Ultraestrutura, Centro de Tecnologias Estratégicas do Nordeste (CETENE), Recife, PE, Brazil. 6. Universidade Federal de Pernambuco (UFPE), Campus Vitória de Santo Antão, PE, Brazil. 7. Programa de Pós-graduação em Biotecnologia/RENORBIO, Universidade Federal de Pernambuco, Recife, PE, Brazil.
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.
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.
Authors: Carlos Eduardo Medina-De la Garza; Armando Salvador Flores-Torres; Marisela García-Hernández; María de Los Ángeles Castro-Corona Journal: Med Hypotheses Date: 2022-01-25 Impact factor: 1.538