Silymarin protects against acute ethanol-induced hepatotoxicity in mice
Silymarin protects against acute ethanol-induced hepatotoxicity in mice
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DOI：
10.1111/j.1530-0277.2006.00063.x
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发表时间：
2006-03-01
影响因子：
3.2
通讯作者：
McClain, C
中科院分区：
文献类型：
--
作者：
Song, ZY;Deaciuc, I;McClain, C
背景：积累的证据表明，氧化应激和细胞因子异常产生，尤其是肿瘤坏死因子-α（TNF），在酒精性肝病（ALD）的发病机制中发挥着重要的病因作用。具有抗氧化和抗炎特性（尤其是抗 TNF 产生）的药物代表了 ALD 的有前途的治疗干预措施。我们研究了水飞蓟素对急性乙醇（EtOH）引起的肝损伤的影响及其可能机制。方法：将9周龄小鼠分为4组，对照组、水飞蓟素治疗组、EtOH治疗组和水飞蓟素/EtOH治疗组，每组6只小鼠。由于对照和水飞蓟素值几乎相同，因此为了便于查看，仅显示对照处理。乙醇处理的小鼠每 12 小时通过管饲法接受 EtOH [5 g/kg 体重 (BW)]，总共 3 剂。对照小鼠接受等热量麦芽糖溶液。在水飞蓟素/EtOH组中，将水飞蓟素溶解在EtOH中并与EtOH同时以200mg/kg BW的剂量灌胃。最后一次给药后4小时，将小鼠麻醉，随后测量血清丙氨酸氨基转移酶（ALT）水平、肝脂质过氧化、肝细胞色素P450 2E1的酶活性、肝TNF-α和谷胱甘肽（GSH）水平。通过苏木精和伊红染色评估组织病理学变化。结果：急性EtOH给药引起显着的肝微泡脂肪变性，伴有轻度坏死和血清ALT活性升高，诱导肝脏GSH显着降低，同时脂质过氧化增强，并增加肝脏TNF的产生。补充标准化水飞蓟素可减轻急性乙醇给药引起的这些不良变化。结论：水飞蓟素可防止急性乙醇给药引起的肝损伤。鉴于其无毒性质，其抗氧化应激和抗炎特性可能被开发为酒精性肝病的有效治疗剂。
Background: Accumulated evidence has demonstrated that both oxidative stress and abnormal cytokine production, especially tumor necrosis factor-alpha (TNF), play important etiological roles in the pathogenesis of alcoholic liver disease (ALD). Agents that have both antioxidant and anti-inflammation properties, particularly anti-TNF production, represent promising therapeutic interventions for ALD. We investigated the effects and the possible mechanism(s) of silymarin on liver injury induced by acute ethanol (EtOH) administration.Methods: Nine-week-old mice were divided into 4 groups, control, silymarin treatment, EtOH treatment, and silymarin/EtOH treatment, with 6 mice in each group. Because control and silymarin values were virtually identical, only control treatment is shown for ease of viewing. Ethanol-treated mice received EtOH [5 g/kg body weight (BW)] by gavage every 12 hours for a total of 3 doses. Control mice received an isocalorical maltose solution. In the silymarin/EtOH group, silymarin was dissolved in the EtOH and gavaged simultaneously with EtOH at a dose of 200 mg/kg BW. At 4 hours after the last dosing, the mice were anesthetized and subsequent serum alanine aminotransferase (ALT) level, hepatic lipid peroxidation, enzymatic activity of hepatic cytochrome P450 2E1, hepatic TNF-alpha, and glutathione (GSH) levels were measured. Histopathological change was assessed by hematoxylin and eosin staining.Results: Acute EtOH administration caused prominent hepatic microvesicular steatosis with mild necrosis and an elevation of serum ALT activity, induced a significant decrease in hepatic GSH in conjunction with enhanced lipid peroxidation, and increased hepatic TNF production. Supplementation with a standardized silymarin attenuated these adverse changes induced by acute EtOH administration.Conclusions: Silymarin protects against the liver injury caused by acute EtOH administration. In view of its nontoxic nature, it may be developed as an effective therapeutic agent for alcohol-induced liver disease by its antioxidative stress and anti-inflammatory features.