Avaliação dos efeitos celulares e moleculares da silimarina em linhagem de células estreladas hepáticas (LX-2): controle do processo fibrosante hepático e alterações no metabolismo de lipídeos
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Data
2019-02-27
Autores
Silva, Caio Mateus da
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Universidade Estadual Paulista (Unesp)
Resumo
As doenças hepáticas são um grave problema de saúde mundial. Muitas patologias crônicas acometem o fígado e em comum à essas doenças há o surgimento do processo fibrosante. A fibrose hepática é caracterizada pela deposição de fibras cicatriciais e alterações na matriz extracelular do órgão. O estabelecimento da fibrose ocorre quando células estreladas hepáticas (CEHs) passam de seu fenótipo quiescente para o ativado. Essas células em fenótipo ativado, são proliferativas e sintetizadores de elementos da matriz extracelular. Caracteristicamente as CEHs ativadas alteram seu metabolismo lipídico perdendo a capacidade de armazenar gotículas lipídicas em seu citoplasma e alguns autores propõem o controle desse metabolismo para auxiliar a reversão do processo fibrosante hepático. Compostos obtidos através de plantas pode ajudar no tratamento de doenças hepáticas. Nesse contexto, a planta medicinal Silybum marianum é conhecida pelos seus efeitos medicinais. O conjunto de compostos encontrados em seus frutos e sementes são denominados silimarina. A silimarina apresenta efeitos hepatoprotetores, anti-inflamatórios e anti-oxidativos. O presente trabalho teve como objetivo avaliar os efeitos celulares e moleculares da silimarina em linhagem de células estreladas hepáticas (LX-2) e seu potencial de reversão da fibrose hepática e o controle do metabolismo lipídico. Além disso, o efeito do composto no metabolismo lipídico foi avaliado em um modelo de co-cultivo entre células hepáticas (HepG2) e as LX-2. Os resultados apontam que a concentração de 100 µM de silimarina atua no controle do processo fibrosante, reduzindo a sinalização pró-fibrótica das células LX-2. Essa mesma concentração é capaz de restaurar a hoemostase do metabolismo lipídico, após alterações ocasionadas pelo tratamento das células com dimetil-sulfóxido. Uma concentração mais elevada de silimarina (150 µM) conduz as LX-2 para um acúmulo de ácidos graxos e triglicerídeos. Mas modelos de co-cultivos entre hepatócitos (HepG2) e LX-2 demonstram que essa é uma estratégia celular para restaurar a homeostase celular após o descontrole do metabolismo de lipídeos causados pelo DMSO. Em conclusão a silimarina apresenta efeitos positivos para a reversão do quadro fibrótico, além disso, seu potencial hepatoprotetor é confirmado. Sendo assim, a silimarina demonstra grande potencial para auxiliar em terapias voltadas ao tratamento da fibrose hepática.
Liver diseases are a serious health problem worldwide. Many chronic pathologies affect the liver and in common to these diseases, there are the appearance of the fibrotic process. The hepatic fibrosis is characterized by the deposition of scar tissue and changes in the extracellular matrix of the organ. The establishment of the fibrotic process occurs when hepatic stellate cells (HSCs) transdifferentiate from their quiescent to their activated phenotype. These activated cells are proliferative and synthesizes extracellular matrix elements. Characteristically the activated HSCs change their lipid metabolism losing the ability to store lipid droplets in their cytoplasm. Some authors proposes that the control of the lipid metabolism contributes to the reversal of the hepatic fibrosing process. Compounds obtained through plants can help in the treatment of liver diseases. In this context, the medicinal plant Silybum marianum is known for its medicinal effects. The set of compounds found in their fruits and seeds are known as silymarin. Silymarin has hepatoprotective, anti-inflammatory and anti-oxidative effects. The aim of the present study was to evaluate the cellular and molecular effects of silymarin in the hepatic stellate cell line (LX-2) and its potential for reversion of hepatic fibrosis and control of lipid metabolism. In addition, the effect of the compound on lipid metabolism was evaluated in a co-culture model between hepatic cells (HepG2) and LX-2. The results indicate that the concentration of 100 μM of silymarin acts as a regulator of the fibrotic process, reducing the pro-fibrotic signaling of LX-2 cells. This same concentration is able to restore the hoemostasis of the lipid metabolism, after changes caused by the treatment of the cells with dimethyl sulfoxide. A higher concentration of silymarin (150 μM) leads the LX-2 cells towards an accumulation of fatty acids and triglycerides. However, the co-culture models between hepatocytes (HepG2) and HSCs (LX-2) demonstrate this as a cellular strategy to restore cellular homeostasis after the imbalance in the lipid metabolism caused by DMSO. In conclusion, the silymarin has positive effects in the fibrotic reversion; in addition, its hepatoprotective potential is confirmed. Thus, silymarin shows great potential to assist in therapies aimed at the treatment of hepatic fibrosis.
Liver diseases are a serious health problem worldwide. Many chronic pathologies affect the liver and in common to these diseases, there are the appearance of the fibrotic process. The hepatic fibrosis is characterized by the deposition of scar tissue and changes in the extracellular matrix of the organ. The establishment of the fibrotic process occurs when hepatic stellate cells (HSCs) transdifferentiate from their quiescent to their activated phenotype. These activated cells are proliferative and synthesizes extracellular matrix elements. Characteristically the activated HSCs change their lipid metabolism losing the ability to store lipid droplets in their cytoplasm. Some authors proposes that the control of the lipid metabolism contributes to the reversal of the hepatic fibrosing process. Compounds obtained through plants can help in the treatment of liver diseases. In this context, the medicinal plant Silybum marianum is known for its medicinal effects. The set of compounds found in their fruits and seeds are known as silymarin. Silymarin has hepatoprotective, anti-inflammatory and anti-oxidative effects. The aim of the present study was to evaluate the cellular and molecular effects of silymarin in the hepatic stellate cell line (LX-2) and its potential for reversion of hepatic fibrosis and control of lipid metabolism. In addition, the effect of the compound on lipid metabolism was evaluated in a co-culture model between hepatic cells (HepG2) and LX-2. The results indicate that the concentration of 100 μM of silymarin acts as a regulator of the fibrotic process, reducing the pro-fibrotic signaling of LX-2 cells. This same concentration is able to restore the hoemostasis of the lipid metabolism, after changes caused by the treatment of the cells with dimethyl sulfoxide. A higher concentration of silymarin (150 μM) leads the LX-2 cells towards an accumulation of fatty acids and triglycerides. However, the co-culture models between hepatocytes (HepG2) and HSCs (LX-2) demonstrate this as a cellular strategy to restore cellular homeostasis after the imbalance in the lipid metabolism caused by DMSO. In conclusion, the silymarin has positive effects in the fibrotic reversion; in addition, its hepatoprotective potential is confirmed. Thus, silymarin shows great potential to assist in therapies aimed at the treatment of hepatic fibrosis.
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Palavras-chave
Planta medicinal, Cultura de células, Silybum marianum, DMSO, Medicinal plant, Cell culture