Developing and Characterizing a Mouse Model of Hepatotoxicity Using Oral Pyrrolizidine Alkaloid (Monocrotaline) Administration, with Potentiation of the Liver Injury by Co-administration of LPS

Developing and Characterizing a Mouse Model of Hepatotoxicity Using Oral Pyrrolizidine Alkaloid (Monocrotaline) Administration, with Potentiation of the Liver Injury by Co-administration of LPS
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使用口服吡咯里西啶生物碱(野百合碱)开发和表征小鼠肝毒性模型,并通过联合使用 LPS 增强肝损伤

DOI:
10.1177/1934578x1000500922
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发表时间:
2010
影响因子:
1.8
通讯作者:
M. Ashfaq
M. Ashfaq
中科院分区:
医学4区
文献类型:
--
作者:
M. Abdel;M. Hammad;L. Walker;M. Ashfaq

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Oral administration of xenobiotics is preferable for research in In Vivo models because it mimics the real life situation of human subjects. Therefore, oral (po) monocrotaline (MCT) (a common contaminant of dietary supplements)/intraperitoneal (ip) lipopolysaccharides (LPS)-induced liver injury possibly imitates idiosyncratic hepatotoxicity in humans. Cytokines, for example interleukin-1β (IL-1β) and transforming growth factor beta (TGF-β) are known to play a role in the development of toxicity and repair processes, respectively. The purpose of this study was to develop and characterize a model of po MCT/ip LPS hepatotoxicity which may elucidate the mechanisms of injury. ND4 male mice were given MCT (200 mg/kg) followed 4 h later by LPS (6 mg/kg). Blood samples were drawn for plasma chemistry and IL-1β. Animals were euthanized and livers were harvested at different time points. We have shown that MCT/LPS cotreatment results in significant elevation of plasma alanine aminotransferase (ALT), CRP, IL-1β and TGF-β. Histopathological evaluation revealed diffuse degenerative injury. In summary, we have established a reproducible in vivo model of hepatotoxicity by po MCT/ip LPS cotreatment that may closely mimic real life idiosyncratic hepatotoxicity.
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