1 Department of Gastroenterology, The First Affiliated Hospital of Dalian Medical University , Dalian, Liaoning Province, China .
J Med Food. 2014 Jun;17(6):663-9. doi: 10.1089/jmf.2013.2834. Epub 2014 Apr 8.
Liver steatosis is characterized by lipid dysregulation and fat accumulation in the liver and can lead to oxidative stress in liver. Since proanthocyanidins are present in plant-based foods and have powerful antioxidant properties, we investigated whether proanthocyanidins can prevent oxidative stress and subsequent liver injury. Carbon tetrachloride (CCl4) treatment can cause steatosis in rats that models both alcoholic and non-alcoholic fatty liver disease in humans. We pre-treated rats by oral administration of proanthocyanidins extracted from grape seeds 7 days prior to intragastrically administering CCl4. Proanthocyanidin treatment continued for an additional 2 weeks, after which time liver and serum were harvested, and mediators of liver injury, oxidative stress, and histological features were evaluated. CCl4-treated rats exhibited significant increases in the following parameters as compared to non-treated rats: fat droplets in the liver, liver injury (ALT, AST), and DNA damage (8-OHdG). Additionally, CCl4 treatment decreased antioxidant enzymes SOD, GSH, GPX, and CAT in the liver due to their rapid depletion after battling against oxidative stress. Compared to CCl4-treated rats, treatment with proanthocyanidins effectively suppressed lipid accumulation, liver injury, DNA damage, as well as restored antioxidant enzyme levels. Further investigation revealed that proanthocyanidins treatment also inhibited expression of CYP2E1 in liver, which prevented the initial step of generating free radicals from CCl4. The data presented here show that treatment with orally administered proanthocyanidins prevented liver injury in the CCl4-induced steatosis model, likely through exerting antioxidant actions to suppress oxidative stress and inhibiting the free radical-generating CYP2E1 enzyme.
肝脂肪变性的特征是肝脏中脂质失调和脂肪堆积，并可导致肝脏氧化应激。由于原花青素存在于植物性食物中，具有强大的抗氧化特性，我们研究了原花青素是否可以预防氧化应激和随后的肝损伤。四氯化碳 (CCl4) 处理可引起大鼠肝脂肪变性，该模型模拟了人类的酒精性和非酒精性脂肪性肝病。我们通过口服葡萄籽中原花青素预处理大鼠，在胃内给予 CCl4 前 7 天。原花青素治疗继续进行另外 2 周，之后收获肝脏和血清，并评估肝损伤、氧化应激和组织学特征的介质。与未处理的大鼠相比，CCl4 处理的大鼠表现出以下参数的显着增加：肝脏中的脂肪滴、肝损伤 (ALT、AST) 和 DNA 损伤 (8-OHdG)。此外，由于 CCl4 处理后抗氧化酶 SOD、GSH、GPX 和 CAT 迅速耗竭，因此 CCl4 处理降低了肝脏中的这些酶。与 CCl4 处理的大鼠相比，用原花青素治疗有效地抑制了脂质积累、肝损伤、DNA 损伤，并恢复了抗氧化酶水平。进一步的研究表明，原花青素治疗还抑制了 CYP2E1 在肝脏中的表达，从而阻止了 CCl4 产生自由基的初始步骤。这里呈现的数据表明，口服给予原花青素可预防 CCl4 诱导的脂肪变性模型中的肝损伤，可能通过发挥抗氧化作用来抑制氧化应激并抑制产生自由基的 CYP2E1 酶。
