Augmenter of liver regeneration protects against carbon tetrachloride-induced liver injury by promoting autophagy in mice

Abstract

BackgroundAugmenter of liver regeneration (ALR) exerts strong hepatoprotective properties in various animal models of liver injury, but its protective mechanisms have not yet been explored. Autophagy is a recently recognized rudimentary cellular response to inflammation and injury. The aim of this study was to test the hypothesis that ALR may protect against acute liver injury through the autophagic pathway.MethodsThe level and role of ALR in liver injury were studied in a mouse model of acute liver injury induced by carbon tetrachloride (CCl4). The effect of ALR on autophagy was analyzed in vitro and in vivo. After autophagy was inhibited by 3-methyladenine (3-MA), apoptosis and proliferation were detected in the mouse model with acute liver injury. The ALR and autophagic levels were measured in patients with liver cirrhosis (LC) and acute liver failure (ALF), respectively.ResultsDuring the progression of acute liver injury, the ALR levels increased slightly in early stage and significantly decreased in late stage in mice Treatment with an ALR plasmid via tail vein injection protected mice against acute liver injury. The protective effect of ALR relied on the induction of autophagy, which was supported by the following evidence: (1) ALR overexpression directly induced autophagy flux in vitro and in vivo; and (2) ALR treatment suppressed apoptosis and promoted proliferation in mice exposed to CCl4, but the inhibition of autophagy reversed these effects. More importantly, the ALR levels decreased in patients with LC and ALF compared with normal controls.ConclusionWe demonstrated that ALR ameliorated liver injury via an autophagic mechanism, which indicates a potential therapeutic application for liver injury.

Bicyclol Attenuates Acute Liver Injury by Activating Autophagy, Anti-Oxidative and Anti-Inflammatory Capabilities in Mice

“…In this study, bicyclol treatment also augmented the expression level of other autophagy-related proteins including ATG7 and Beclin-1. Specially, ATG7 is a key factor in the ubiquitin-like pathway of LC3 lipidation, while Beclin-1 interacts with VPS34, HMGB1 and Rubicon for modulating the autophagy process (Itakura and Mizushima, 2010;Shi et al, 2017 autophagic flux since they involve in the initiation and closure of the autophagic vesicle, respectively (Itakura and Mizushima, 2010). Additionally, TEM images represented that bicyclol increased the number of autophagic vacuoles, and autophagic flux was promoted by bicyclol as indicated by the increase in autophagosomes and autolysosomes in AML12 cells.…”

“…It is known that the hepatic metabolism of CCl 4 releases extensive ROS, which in turn leads to autophagy, inflammation, and tissue necrosis (Xie et al, 2015;Shi et al, 2017;Wang et al, 2018). In addition, oxidative stress also contributes to infl ammation by activating NLRP3 inflammasome.…”

Augmenter of liver regeneration enhances cell proliferation through the microRNA‐26a/Akt/cyclin D1 pathway in hepatic cells

“…Shi et al . showed that ALR protected the liver against carbon tetrachloride‐induced liver injury by promoting autophagy in mice . Recently, it was shown that ALR knockdown resulted in the inhibition of DNA synthesis .…”

Propolis Extract Attenuates Sepsis-Induced Hepatotoxicity and Neurotoxicity in Male Rats

“…The injury progresses from active hepatocellular dysfunction into liver damage, then into liver failure (Dkhil et al, 2018a). Pathogenesis of acute liver injury were known to involve a complex interplay of oxidative stress, apoptosis, inflammation and necrosis (Shi et al, 2017). Sepsis causes various complications as cardiac dysfunction, liver disorder, kidney and brain injury as well.…”