Abstract
Inflammatory response and oxidative stress are considered to play an important role in the development of acute liver injury induced by carbon tetrachloride (CCl4) and galactosamine (GalN)/lipopolysaccharides (LPS). Esculentoside A (EsA), isolated from the Chinese herb phytolacca esculenta, has the effect of modulating immune response, cell proliferation and apoptosis as well as anti-inflammatory effects. The present study is to evaluate the protective effect of EsA on CCl4 and GalN/LPS-induced acute liver injury. In vitro, CCK-8 assays showed that EsA had no cytotoxicity, while it significantly reduced levels of TNF-α and cell death rate challenged by CCl4. Moreover, EsA treatment up-regulated PPAR-γ expression of LO2 cells and reduced levels of reactive oxygen species (ROS) challenged by CCl4. In vivo, EsA prevented mice from CCl4-induced liver histopathological damage. In addition, levels of AST and ALT were significantly decreased by EsA treatment. Furthermore, the mice treated with EsA had a lower level of TNF-α, Interleukin (IL)-1β and IL-6 in mRNA expression. EsA prevented MDA release and increased GSH-Px activity in liver tissues. Immunohistochemical staining showed that over-expression of F4/80 and CD11b were markedly inhibited by EsA. The western bolt results showed that EsA significantly inhibited CCl4-induced phosphonated IkBalpha (P-IκB) and ERK. Furthermore, EsA treatment also alleviated GalN/LPS-induced acute liver injury on liver enzyme and histopathological damage. Unfortunately, our results exhibited that EsA had no effects on CCl4-induced hepatocyte apoptosis which were showed by TUNEL staining and Bax, Caspase-3 and cleaved Caspase-3 expression. Our results proved that EsA treatment attenuated CCl4 and GalN/LPS-induced acute liver injury in mice and its protective effects might be involved in inhibiting inflammatory response and oxidative stress, but not apoptosis with its underlying mechanism associated with PPAR-γ, NF-κB and ERK signal pathways.
Highlights
Liver is one of the most important internal organs in human body with multiple of functions such as detoxification, protein synthesis, and production of biochemicals necessary for digestion etc [1]
Our results proved that Esculentoside A (EsA) treatment attenuated CCl4 and GalN/LPS-induced acute liver injury in mice and its protective effects might be involved in inhibiting inflammatory response and oxidative stress, but not apoptosis with its underlying mechanism associated with PPAR-c, NF-kB and ERK signal pathways
We found that EsA treatment attenuated CCl4 and GalN/LPS-induced acute liver injury and its protective effect might be involved in inhibiting inflammatory response and oxidative stress, the underlying mechanism was associated with PPAR-c, ERK and NF-kB signal pathways
Summary
Liver is one of the most important internal organs in human body with multiple of functions such as detoxification, protein synthesis, and production of biochemicals necessary for digestion etc [1]. Acute liver injury is usually referred as the rapid development of hepatocellular dysfunction with a poor prognosis It frequently results from the induction of drugs, virus infection, toxins or hepatic ischemic-reperfusion injury, et al [3,4]. In the presence of excess oxygen, NCCl3 can transform into trichloromethylperoxy radical CCl3OON, another highly reactive species [2,3] This molecule can decrease polyunsaturated fatty acids and cause lipid peroxidation, which contributes to severe cellular damage [6,7]. Another classical animal model achieved by intraperitoneal injection of GalN/LPS has often been used for the study of acute liver injury. Hepatocytes strive to clear LPS, which is followed by inflammatory response, oxidative stress and even hepatic necrosis [8]
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