Institute of Toxicology, School of Public Health, Shandong University, 44 Wenhua West Road, Shandong, Jinan 250012, PR China.
Food Chem Toxicol. 2012 Mar;50(3-4):485-91. doi: 10.1016/j.fct.2011.11.030. Epub 2011 Nov 26.
Garlic oil (GO) has been shown to partially attenuate ethanol-induced fatty liver, but the underlying mechanisms remain unclear. The current study was designed to evaluate the protective effects of GO against ethanol-induced steatosis in vitro and in vivo, and to explore potential mechanisms by investigating the sterol regulatory element binding protein-1c (SREBP-1c), peroxisome proliferators-activated receptor-α (PPAR-α), cytochrome P4502E1 (CYP2E1), and etc. In the in vitro study, human normal cell LO2 was exposed to 100 mM ethanol in the presence or absence of GO for 24 h. We found that ethanol increased the protein levels of n-SREBP-1c and CYP2E1, but decreased the protein levels of PPAR-α, which was significantly attenuated by GO co-treatment. In the in vivo study, male Kun-Ming mice were pretreated with single dose of GO (50-200 mg/kg body weight) at 2 h before ethanol (4.8 g/kg body weight) exposure. The changes of n-SREBP-1c, PPAR-α and CYP2E1 were paralleled well to those of in vitro study. Furthermore, GO significantly reduced the protein levels of fatty acid synthase (FAS), and suppressed ethanol-induced hepatic mitochondrial dysfunction. These results suggested that GO had the potential to ameliorate alcoholic steatosis which might be related to its modulation on SREBP-1c, PPAR-α, and CYP2E1.
大蒜油(GO)已被证明可部分减轻乙醇诱导的脂肪肝,但潜在机制尚不清楚。本研究旨在评估 GO 对体外和体内乙醇诱导的脂肪变性的保护作用,并通过研究固醇调节元件结合蛋白-1c(SREBP-1c)、过氧化物酶体增殖物激活受体-α(PPAR-α)、细胞色素 P4502E1(CYP2E1)等,探讨潜在机制。在体外研究中,人正常细胞 LO2 在存在或不存在 GO 的情况下暴露于 100mM 乙醇 24 小时。我们发现乙醇增加了 n-SREBP-1c 和 CYP2E1 的蛋白水平,但降低了 PPAR-α 的蛋白水平,GO 共同处理明显减轻了这种情况。在体内研究中,雄性昆明小鼠在乙醇(4.8g/kg 体重)暴露前 2 小时给予单次剂量 GO(50-200mg/kg 体重)预处理。n-SREBP-1c、PPAR-α 和 CYP2E1 的变化与体外研究一致。此外,GO 显著降低了脂肪酸合酶(FAS)的蛋白水平,并抑制了乙醇诱导的肝线粒体功能障碍。这些结果表明,GO 具有改善酒精性脂肪变性的潜力,这可能与其对 SREBP-1c、PPAR-α 和 CYP2E1 的调节有关。