Pulmonary Toxicity and Metabolic Activation of Dauricine in CD-1 Mice
文献类型：期刊论文
| 作者 | Jin, Hua2; Dai, Jieyu2; Chen, Xiaoyan1 ; Liu, Jia1; Zhong, Dafang1; Gu, Yansong3; Zheng, Jiang2
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| 刊名 | JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
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| 出版日期 | 2010-03 |
| 卷号 | 332期号:3页码:738-746 |
| ISSN号 | 0022-3565 |
| DOI | 10.1124/jpet.109.162297 |
| 文献子类 | Article |
| 英文摘要 | Dauricine is the major bioactive component isolated from the roots of Menispermum dauricum D.C. and has shown promising pharmacological activities with a great potential for clinic use. However, the adverse effects and toxicity of the alkaloid are unfortunately ignored. The objective of the current study was to evaluate the toxicity of dauricine in vitro and in vivo. Mice (CD-1) were treated intraperitoneally with dauricine at various doses, and sera and lung lavage fluids were collected after 24 h of treatment. No changes in serum aspartate aminotransferase, alanine aminotransferase, and blood urea nitrogen were noticed, whereas a dose-dependent increase in lactate dehydrogenase activity was observed in lung lavage fluids. Ethidium-based staining studies showed that remarkable cells lost membrane integrity in the lungs of the animals treated with dauricine at 150 mg/kg. Histopathological evaluation of lungs of mice showed that dauricine at the same dose caused significant alveolar edema and hemorrhage. Exposure to dauricine at 40 mu M for 24 h resulted in up to 60% cell death in human lung cell lines BEAS-2B, WI-38, and A549. Ketoconazole showed protective effect on the pulmonary injury in mice given dauricine. A quinone methide metabolite of dauricine was identified in mouse lung microsomal incubations, and the presence of ketoconazole in the microsomal incubations suppressed the formation of the quinone methide metabolite. In conclusion, dauricine produced pulmonary injury in CD-1 mice. The pulmonary toxicity appears to depend on the metabolism of dauricine mediated by CYP3A. The electrophilic quinone methide metabolite probably plays an important role in the pulmonary toxicity induced by dauricine. |
| WOS关键词 | QUINONE METHIDE METABOLITES ; HUMAN LIVER-MICROSOMES ; MURINE CLARA CELLS ; BISBENZYLISOQUINOLINE ALKALOIDS ; DNA-ADDUCTS ; HUMAN LUNG ; IDENTIFICATION ; RAT ; CYTOTOXICITY ; SPECTROMETRY |
| 资助项目 | National Natural Science Foundation of China[30873119] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000274800200006 |
| 出版者 | AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278969]  |
| 专题 | 上海药物代谢研究中心 |
| 通讯作者 | Zheng, Jiang |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 200031, Peoples R China; 2.Univ Washington, Ctr Dev Therapeut, Div Gastroenterol, Seattle Childrens Res Inst,Dept Pediat, Seattle, WA 98101 USA; 3.Univ Washington, Div Radiobiol, Dept Radiat Oncol, Seattle, WA 98101 USA |
| 推荐引用方式 GB/T 7714 | Jin, Hua,Dai, Jieyu,Chen, Xiaoyan,et al. Pulmonary Toxicity and Metabolic Activation of Dauricine in CD-1 Mice[J]. JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS,2010,332(3):738-746. |
| APA | Jin, Hua.,Dai, Jieyu.,Chen, Xiaoyan.,Liu, Jia.,Zhong, Dafang.,...&Zheng, Jiang.(2010).Pulmonary Toxicity and Metabolic Activation of Dauricine in CD-1 Mice.JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS,332(3),738-746. |
| MLA | Jin, Hua,et al."Pulmonary Toxicity and Metabolic Activation of Dauricine in CD-1 Mice".JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS 332.3(2010):738-746. |
入库方式： OAI收割
来源：上海药物研究所
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