P-Hydroxyacetophenone Ameliorates Alcohol-Induced Steatosis and Oxidative Stress via the NF-κB Signaling Pathway in Zebrafish and Hepatocytes
Sha Huang, Sha Huang, Chuying Zhou, Ting Zeng, Yujia Li, Yuqi Lai, Chan Mo, Yuyao Chen, Shaohui Huang, Shaohui Huang, Zhiping Lv, Lei Gao
Abstract
Alcoholic liver disease (ALD), recognized as an important health problem worldwide, is a direct consequence of alcohol consumption, which can induce alcoholic fatty liver, alcoholic steatohepatitis, fibrosis and cirrhosis. p-Hydroxyacetophenone (p-HAP) is mainly used as a hepatoprotective and choleretic compound and has anti-hepatitis B, antioxidation and anti-inflammatory effects. However, no experimental report has focused on p-HAP in ALD, and the effect and mechanism of p-HAP in ALD remains a mystery. In addition, there is no research on p-HAP in the treatment of ALD. The potential molecular mechanisms of p-HAP against acute alcoholic liver injury remain unknown. In this study, we aimed to investigate whether p-HAP alleviates ALD and to elucidate the underlying molecular mechanisms. At 4 days postfertilization (dpf), zebrafish larvae were exposed to 350 mmol/L ethanol for 32 h and then treated with p-HAP for 48 h. We chose different endpoints, such as morphological changes in liver shape and size, histological changes, oxidative stress-related free radical levels, apoptosis and NF-κB expression, to verify the essential impact of p-HAP in alcohol-induced liver lesions. Subsequent experiments, including Oil Red O, Nile Red, and pathological hematoxylin and eosin (H&E) staining, immunochemistry, Western blot analysis and TUNEL staining, revealed that p-HAP treatment reduced alcoholic hepatic steatosis in a dose-dependent manner. Specifically, the 50 μM dose resulted in an almost normal response. This finding suggested that p-HAP might inhibit alcoholic-induced liver steatosis and injury by attenuating lipid accumulation and reducing oxidative stress and apoptosis via the NF-κB signaling pathway.