Lee Kyung Jin, Jeong Hye Gwang
Department of Biology, Chonnam National University, Kwangju, South Korea.
Food Chem Toxicol. 2002 Apr;40(4):517-25. doi: 10.1016/s0278-6915(01)00104-1.
The protective effects of a Platycodi radix (Changkil: CK), the root of Platycodon grandiflorum A. DC (Campanulaceae) on carbon tetrachloride (CC14)-induced hepatotoxicity and the possible mechanisms involved in this protection were investigated in mice. Pretreatment with CK prior to the administration of CC14 significantly prevented the increased serum enzymatic activities of alanine and aspartate aminotransferase in a dose-dependent manner. In addition, pretreatment with CK also significantly prevented the elevation of hepatic malondialdehyde formation and the depletion of reduced glutathione content in the liver of CC14-intoxicated mice. However, hepatic reduced glutathione levels and glutathione S-transferase activities were not affected by treatment with CK alone. CC14-induced hepatotoxicity was also essentially prevented, as indicated by a liver histopathologic study. The effects of CK on the cytochrome P450 (P450) 2E1, the major isozyme involved in CC14 bioactivation were also investigated. Treatment of mice with CK resulted in a significant decrease of P450 2E1-dependent p-nitrophenol and aniline hydroxylation in a dose-dependent manner. CK showed antioxidant effects in FeCl2-ascorbate-induced lipid peroxidation in mice liver homogenate and in superoxide radical scavenging activity. Our results suggest that the protective effects of CK against CC14-induced hepatotoxicity possibly involve mechanisms related to its ability to block P450-mediated CC14 bioactivation and free radical scavenging effects.
在小鼠中研究了桔梗(Changkil: CK),即桔梗科植物桔梗(Platycodon grandiflorum A. DC)的根,对四氯化碳(CC14)诱导的肝毒性的保护作用及其保护作用可能涉及的机制。在给予CC14之前用CK预处理以剂量依赖性方式显著预防了丙氨酸和天冬氨酸转氨酶血清酶活性的升高。此外,用CK预处理还显著预防了CC14中毒小鼠肝脏中丙二醛形成的升高和还原型谷胱甘肽含量的消耗。然而,单独用CK处理未影响肝脏中还原型谷胱甘肽水平和谷胱甘肽S -转移酶活性。肝脏组织病理学研究表明,CC14诱导的肝毒性也基本得到预防。还研究了CK对细胞色素P450(P450)2E1的影响,P450 2E1是参与CC14生物活化的主要同工酶。用CK处理小鼠导致P450 2E1依赖性对硝基苯酚和苯胺羟基化以剂量依赖性方式显著降低。CK在小鼠肝脏匀浆中对FeCl2 -抗坏血酸诱导的脂质过氧化以及超氧自由基清除活性方面显示出抗氧化作用。我们的结果表明,CK对CC14诱导的肝毒性的保护作用可能涉及其阻断P450介导的CC14生物活化的能力和自由基清除作用相关的机制。