Abstract
BackgroundBabao Dan (BBD), a traditional Chinese medicine, has been used as a complementary and alternative medicine to treat multifarious liver diseases. In this study, we aimed to observe its protective effect on ethanol-induced liver injury and explore potential mechanisms.MethodsMice pretreated with BBD (0.125, 0.25 and 0.5 g/kg BW) were administrated by ethanol gavage (5 g/kg BW). Liver injury biomarkers and hepatic redox parameters were evaluated by histopathology as well as serum and hepatic content analysis. AML-12 cell was also utilized to determine the efficacy of BBD against ethanol-induced hepatotoxicity.ResultsDrunkenness experiment showed that the latency was significantly increased and the drunken sleep time was decreased in mice pretreated with BBD. We then found that BBD could reduce hepatic lipid peroxidation and steatosis induced by ethanol exposure. BBD could also suppress ethanol-induced depletion of hepatic antioxidant enzyme. Besides that, BBD treatment lessened the induction of hepatic cytochrome P450 2E1, a major contributor to ethanol-mediated oxidative stress, and up-regulated the expression of nuclear factor erythroid 2-related factor 2 and its two transcriptional targets hemeoxygenase-1 and glutamate-cysteine ligase catalytic subunit. Furthermore, autophagy induced by BBD contributed to hepatoprotection activity.ConclusionsOur results suggest that BBD can markedly dispel acute ethanol-induced hepatotoxicity through multiple pathways including attenuation of ethanol-mediated oxidative stress, enhancement of the oxidative defense systems and activation of autophagy.
Highlights
Alcohol, as a well-known hepatotoxin, is widely consumed as a popular drink in the world [1]
We demonstrated that Babao Dan (BBD) can ameliorate acute ethanol-induced hepatotoxicity through multiple pathways including attenuation of ethanol-mediated oxidative stress, enhancement of the oxidative defense systems and activation of autophagy
BBD protects against acute liver injury caused by ethanol exposure To investigate the hepatoprotective effect of BBD, we first built an acute alcoholic liver damage model in mice and pretreated them with BBD to evaluate the efficacy in vivo
Summary
As a well-known hepatotoxin, is widely consumed as a popular drink in the world [1]. There is a consistent epidemiological and clinical evidence that ethanol performs as a risk factor in various disorders, especially alcoholic liver disease (ALD) [2, 3]. Ethanol ingestion induces the activation and expression of ethanol metabolizing enzyme cytochrome P450 2E1 (CYP2E1) which has been shown to play a major role in ethanol-induced oxidative stress and lipid accumulation. ROS can activate lipid peroxidation chain reactions, resulting in biomembrane dysfunction, membrane antioxidant enzymes inhibition, mitochondria damage and even cell death [12, 13]. The depletion of antioxidant enzymes including superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) as well as the reduction of glutathione (GSH) level, leads to the oxidative stress in liver. CYP2E1-generated oxidative stress inhibition as a potent strategy in preventing ethanol toxicity would likely be promising for ALD precaution. We aimed to observe its protective effect on ethanolinduced liver injury and explore potential mechanisms
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