HEPATOTOXICITY OF GERMANDER (TEUCRIUM-CHAMAEDRYS L) AND ONE OF ITS CONSTITUENT NEOCLERODANE DITERPENES TEUCRIN-A IN THE MOUSE
HEPATOTOXICITY OF GERMANDER (TEUCRIUM-CHAMAEDRYS L) AND ONE OF ITS CONSTITUENT NEOCLERODANE DITERPENES TEUCRIN-A IN THE MOUSE
复制标题
香根草（teucrium-chamaedrys l）及其成分之一新柠檬二萜柚皮素-a对小鼠的肝毒性
DOI：
10.1021/tx00042a020
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发表时间：
1994-11-01
影响因子：
4.1
通讯作者：
NELSON, SD
中科院分区：
文献类型：
--
作者：
KOUZI, SA;MCMURTRY, RJ;NELSON, SD
The hepatotoxicity of the herbal plant germander and that of one of its major furanoneoclerodane diterpenes, teucrin A, were investigated in mice. Teucrin A was found to cause the same midzonal hepatic necrosis as observed with extracts of the powdered plant material. Evidence that bioactivation of teucrin A by cytochromes P450 (P450) to a reactive metabolite(s) is required for initiation of the hepatocellular damage is provided by results of experiments on the induction and inhibition of P450 and from studies on the effects of glutathione depletion. Pretreatment of mice with the P450 inducer phenobarbital enhanced the hepatotoxic response, as indicated by an increase in plasma alanine aminotransferase (ALT) levels and hepatic necrosis, while pretreatment with the P450 inhibitor piperonyl butoxide markedly attenuated the toxic response. Hepatotoxicity of teucrin A also was increased following pretreatment with the inhibitor of glutathione synthesis buthionine sulfoximine. Most importantly, the tetrahydrofuran analog of teucrin A, obtained by selective chemical reduction of the furan ring, was not hepatotoxic, a result that provides strong evidence that oxidation of the furan ring moiety of the neoclerodane diterpenes is involved in the initiation of hepatocellular injury caused by germander.
