Diallyl Trisulfide Protects Rats from Carbon Tetrachloride-Induced Liver Injury
Diallyl Trisulfide Protects Rats from Carbon Tetrachloride-Induced Liver Injury
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DOI：
10.3945/jn.109.109611
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发表时间：
2009-12-01
影响因子：
4.2
通讯作者：
Ariga, Toyohiko
中科院分区：
文献类型：
--
作者：
Hosono-Fukao, Tomomi;Hosono, Takashi;Ariga, Toyohiko
人们发现烷基硫醚具有大蒜的抗癌、抗血栓和抗氧化作用。我们试图确定硫化物最有效的结构，该结构对四氯化碳 (CCl4) 诱导的大鼠急性肝损伤具有保肝作用。大鼠用二烯丙基三硫化物（DATS）预处理。剂量为500μmol/kg体重，连续5天。第 6 天，静脉注射 CCl4。剂量为2.5毫升/公斤体重。给予 CCl4 24 小时后，处死大鼠并收集血浆和肝脏样本。 DATS预处理显着抑制CCl4诱导的血浆天冬氨酸转氨酶和丙氨酸转氨酶活性升高(P < 0.05)。组织学观察支持保肝作用。蛋白质印迹和分光光度分析表明，DATS 抑制细胞色素 P450 2E1 活性及其蛋白水平，并提高谷胱甘肽 S-转移酶的活性及其蛋白水平。二丙基三硫醚 (DPTS) 是 DATS 的饱和烷基链类似物，不会影响 CCl4 引起的肝毒性或药物代谢酶。这些结果表明三硫化物的保肝活性是由于它们对药物代谢酶的调节。此外，还研究了 DATS 和 DPTS 等 6 种烷（烯）基三硫化物对大鼠 II 相酶活性的影响。烷(烯)基三硫化物通过注射给药。 (500μmol/kg体重)给大鼠，连续5天。只有含烯丙基的 DATS 和烯丙基甲基三硫醚增强了这些活性。 J.努特尔。 139：2252-2256，2009。
Alk(en)yl sulfides have been found to be responsible for the anticancer, antithrombotic, and antioxidant effects of garlic. We sought to identify the most potent structure of sulfides that exhibits a hepatoprotective effect against carbon tetrachloride (CCl4)-induced acute liver injury in rats. Rats were pretreated with diallyl trisulfide (DATS) i.g. at a dose of 500 mu mol/kg body weight for 5 d. On d 6, CCl4 was administered i.g. at a dose of 2.5 mL/kg body weight. Twenty-four hours after CCl4 administration, rats were killed and plasma and liver samples collected. DATS pretreatment significantly suppressed the CCl4-induced elevation of plasma aspartate aminotransferase and alanine aminotransferase activities (P < 0.05). Histological observations supported the hepatoprotective effects. Western blot and spectrophotometric analyses indicated that DATS suppressed cytochrome P450 2E1 activity and its protein level and elevated those of glutathione S-transferase. Dipropyl trisulfide (DPTS), which is a saturated alkyl chain analogue of DATS, did not affect CCl4-induced liver toxicity or drug-metabolizing enzymes. These results suggest that hepatoprotective activity of trisulfides is due to their regulation of drug-metabolizing enzymes. Furthermore, the effects of 6 kinds of alk(en)yl trisulfides, including DATS and DPTS, on phase II enzyme activity were examined in rats. Alk(en)yl trisulfides were administered i.g. (500 mu mol/kg body weight) to rats for 5 d. Only the allyl group-containing DATS and allyl methyl trisulfide enhanced these activities. J. Nutr. 139: 2252-2256, 2009.