Wang B H, Zuzel K A, Rahman K, Billington D
School of Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK.
Toxicology. 1999 Feb 15;132(2-3):215-25. doi: 10.1016/s0300-483x(99)00004-9.
Precision-cut liver slices from phenobarbital-induced rats were incubated for 6 h with the model hepatotoxin bromobenzene (BB) at a final concentration of 1 mM. Severe toxicity was indicated by a decreased K+, adenosine triphosphate and glutathione (GSH) content of the slices, increased release of alanine aminotransferase and lactate dehydrogenase into the medium, and increased formation of thiobarbituric acid reacting substances. Pretreatment of animals for 7 days with aged garlic extract (AGE) (Kyolic) at doses of 2 and 10 ml/kg/day dramatically reduced the toxicity of BB in a dose-dependent manner. The GSH content of liver slices from rats treated with AGE at 2 or 10 ml/kg/day increased by 50 and 80%, respectively. The BB-induced decrease in GSH content was less in slices derived from AGE-treated rats compared with slices from control rats. Pretreatment with AGE did not affect cytochrome P450 when assayed as 7-ethoxycoumarin O-deethylase and 7-pentoxyresorufin O-depentylase activities in hepatic microsomes. Thus, the mechanism by which pretreatment with AGE protects against BB hepatotoxicity involves both an elevation of hepatic GSH content, and a GSH sparing effect, possibly due to conjugation of organosulphur compounds in AGE with toxic BB metabolites. Only this GSH sparing effect was seen in our earlier study on the in vitro hepatoprotective effect of AGE [Wang et al., 1998. Toxicology 126, 213-222].
将苯巴比妥诱导的大鼠的精密肝切片与终浓度为1 mM的模型肝毒素溴苯（BB）孵育6小时。切片中钾离子、三磷酸腺苷和谷胱甘肽（GSH）含量降低，丙氨酸转氨酶和乳酸脱氢酶向培养基中的释放增加，硫代巴比妥酸反应物质的形成增加，表明出现了严重毒性。用老化大蒜提取物（AGE）（Kyolic）以2和10 ml/kg/天的剂量对动物进行7天预处理，以剂量依赖的方式显著降低了BB的毒性。用2或10 ml/kg/天的AGE处理的大鼠的肝切片中GSH含量分别增加了50%和80%。与对照大鼠的切片相比，来自AGE处理大鼠的切片中BB诱导的GSH含量降低较少。当以肝微粒体中的7-乙氧基香豆素O-脱乙基酶和7-戊氧基试卤灵O-脱戊基酶活性进行测定时，AGE预处理不影响细胞色素P450。因此，AGE预处理预防BB肝毒性的机制既涉及肝GSH含量的升高，也涉及GSH节约效应，这可能是由于AGE中的有机硫化合物与有毒的BB代谢物结合所致。在我们早期关于AGE体外肝保护作用的研究中仅观察到了这种GSH节约效应[Wang等人，1998年。毒理学126，213 - 222]。
