Carbon tetrachloride-induced changes in the activity of phase II drug-metabolizing enzyme in the liver of male rats: role of antioxidants
Carbon tetrachloride-induced changes in the activity of phase II drug-metabolizing enzyme in the liver of male rats: role of antioxidants
复制标题
DOI：
10.1016/s0300-483x(01)00429-2
复制
发表时间：
2001-08-28
期刊：
影响因子：
4.5
通讯作者：
Bastawy, M
中科院分区：
文献类型：
--
作者：
Sheweita, SA;Abd El-Gabar, M;Bastawy, M
谷胱甘肽s -转移酶和谷胱甘肽在大多数有毒物质的解毒中起重要作用。本文研究了抗氧化剂（l -抗坏血酸（AA）、维生素E （VE）、大蒜）对四氯化碳诱导的谷氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、谷胱甘肽s -转移酶（GST）活性、谷胱甘肽（GSH）和硫代巴比妥酸活性物质（TBARS）水平变化的保护作用。测定大鼠血浆中谷丙转氨酶（ALT）和谷丙转氨酶（AST）的活性，测定大鼠肝脏中谷丙转氨酶（GST）的活性以及谷胱甘肽（GSH）和TBARS的水平。目前的研究包括两个实验。在第一个实验中，动物在给予AA （100 mg/kg b.w）、VE （100 mg/kg b.w）或大蒜（800 mg/kg b.w）单次口服剂量后，再给予CCl4 （400 mg/kg体重）单次口服剂量。在第二个实验中，大鼠连续12天重复口服抗氧化剂，第13天口服单剂量CCl4, 24 h后处死。CCl4处理的雄性大鼠血浆中ALT和AST的活性以及肝脏中GSH和TBARS的水平均显著升高。另一方面，CCl4单次给药后抑制GST活性。在给予CCl4前单次给药AA、VE或大蒜均不能使CCl4引起的ALT和AST活性变化恢复到正常对照水平。然而，这些药物的重复剂量治疗使这些改变恢复到正常水平。我们观察到，VE比AA和大蒜更有效地将CCl4引起的GST活性抑制恢复到单剂量处理后的正常水平。另一方面，AA和VE在将CCl4诱导的TBARS水平恢复到正常对照水平方面比大蒜更有效。已经观察到，所测试的抗氧化剂能够对抗CCl4的毒性作用，并且当在CCl4之前重复给药时，这种抵消作用更加明显。(C) 2001爱思唯尔科学爱尔兰有限公司版权所有。
Glutathione S-transferases and glutathione play an important role in the detoxification of most toxic agents. In the present study, the protective effects of some antioxidants (L-ascorbic acid (AA), vitamin E (VE) or garlic) on carbon tetrachloride-induced changes in the activity of alanine amino transferase (ALT), aspartate amino transferase (AST), glutathione S-transferase (GST), and the level of glutathione (GSH) and thiobarbituric acid reactive substances (TBARS) were studied. The activities of ALT, and AST were assayed in plasma, whereas the activity of GST and the levels of GSH and TBARS were determined in the livers of rats. The current study included two experiments. In the first experiment, animals received single oral dose of CCl4 (400 mg/kg body weight) after administration of AA (100 mg/kg b.w.), VE (100 mg/kg b.w.) or garlic (800 mg/kg b.w.) as single oral doses. In the second experiment, rats received repeated oral doses of antioxidants for 12 consecutive days followed by a single oral dose of CCl4 on the 13th day and killed after that by 24 h. Treatment of male rats with CCl4 significantly increased the activity of ALT and AST in plasma, and the levels of both GSH and TBARS in the liver. On the other hand, CCl4 inhibited the activity of GST after single dose treatment. Single-dose treatments of rats with AA, VE or garlic prior to the administration of CCl4 could not restore the alterations in the activity of ALT and AST caused by CCl4 to the normal control level. However, repeated dose treatments with these agents restored such alterations to the normal level. We observed that VE is more effective than AA and garlic in restoring the inhibition of GST activity caused by CCl4 to the normal level after single dose treatments. On the other hand, AA and VE are more effective than garlic in restoring the induced TBARS level caused by CCl4 to the normal control level after repeated dose treatments. It has been observed that the tested antioxidants were able to antagonize the toxic effects of CCl4, and such counteracting effects were more pronounced when they were administered as repeated doses prior to administration of CCl4. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.