School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
Department of Liver Diseases, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong 518033, P.R. China.
Oncol Rep. 2017 Nov;38(5):2877-2884. doi: 10.3892/or.2017.5965. Epub 2017 Sep 19.
Alcoholic liver disease (ALD) includes a spectrum of hepatic abnormalities that range from isolated alcoholic steatosis to steatohepatitis and cirrhosis. Naringenin, a predominant flavanone in grapefruit, increases resistance to oxidative stress and inflammation and protects against multiple organ injury in various animal models. However, the specific mechanisms responsible for protection against alcoholic injury are poorly understood. In the present study, we aimed to investigate the effect of naringenin on alcoholic events and the molecular regulatory mechanisms of naringenin in the liver and whole body of zebrafish larvae following exposure to 350 mmol/l ethanol for 32 h. Zebrafish larvae {4 days post‑fertilization (dpf); wild-type (WT) and a transgenic line with liver-specific eGFP expression [Tg(lfabp10α-eGFP)]} were used to establish an alcoholic fatty liver model in order to evaluate the effects of naringenin treatment on anti-alcoholic injury. Naringenin significantly reduced alcoholic liver morphological phenotypes and the expression of alcohol and lipid metabolism-related genes, including cyp2y3, cyp3a65, hmgcra, hmgcrb, fasn, fabp10α, fads2 and echs1, in zebrafish larvae. Naringenin also attenuated hepatic apoptosis in larvae as detected by TUNEL staining, consistent with the expression of critical biomarkers of endoplasmic reticulum stress and of DNA damage genes (chop, gadd45αa and edem1). The present study showed that naringenin inhibited alcohol-induced liver steatosis and injury in zebrafish larvae by reducing apoptosis and DNA damage and by harmonizing alcohol and lipid metabolism.
酒精性肝病（ALD）包括一系列肝脏异常，范围从孤立性酒精性脂肪变性到肝炎和肝硬化。柚皮苷是葡萄柚中的主要类黄酮，可增加对氧化应激和炎症的抵抗力，并在多种动物模型中保护多种器官损伤。然而，导致对酒精损伤的保护的具体机制尚不清楚。在本研究中，我们旨在研究柚皮苷对酒精性事件的影响，以及柚皮苷在斑马鱼幼虫肝脏和全身中的分子调节机制，斑马鱼幼虫{4 天受精后（dpf）; 野生型（WT）和肝脏特异性 GFP 表达的转基因系[Tg（lfabp10α-eGFP）]}用于建立酒精性脂肪肝模型，以评估柚皮苷处理对抗酒精性损伤的影响。柚皮苷显著减轻了酒精性肝形态表型和酒精和脂质代谢相关基因的表达，包括 cyp2y3、cyp3a65、hmgcra、hmgcrb、fasn、fabp10α、fads2 和 echs1，在斑马鱼幼虫中。柚皮苷还通过 TUNEL 染色减弱了幼虫的肝凋亡，这与内质网应激和 DNA 损伤基因（chop、gadd45αa 和 edem1）的关键生物标志物的表达一致。本研究表明，柚皮苷通过减少凋亡和 DNA 损伤以及协调酒精和脂质代谢来抑制酒精诱导的斑马鱼幼虫肝脂肪变性和损伤。
