Saura C. Sahu's Hepatotoxicity: From Genomics to In Vitro and In Vivo Models PDF

By Saura C. Sahu

This booklet addresses all of the present, updated advancements during this medical self-discipline. Liver is the manager metabolizing website within the physique, and therefore, it's a significant objective organ for drug and chemical toxicity. accordingly, hepatotoxicity is a crucial endpoint within the safeguard review of gear and chemical substances. Contributions from prime investigators in hepatotoxicity examine deal with present advancements during this medical self-discipline and speak about use of present leading edge know-how corresponding to microarrays in hepatotoxicity therefore supplying a greater figuring out of hepatotoxins, their interactions and mechanisms of motion. This precious authoritative resource of knowledge is the 1st publication to deal with this subject for almost ten years, making it a necessary source for readers from a variety of disciplines corresponding to toxicology, pharmacology, hepatology, drug toxicity and meals technological know-how.

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Extra info for Hepatotoxicity: From Genomics to In Vitro and In Vivo Models

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Cell viability can be maintained in this device for at least five days and P450 enzymes can be induced by prototypical inducing agents such as dexamethasone. The zonation-based bioreactor is one of the few novel perfusion based system where specific toxicity studies have been designed and conducted. , 2005). These data are supported by the hypothesis that low oxygen concentrations promote glutathione depletion, an important detoxification pathway for the toxic NAPQI acetaminophen mediated metabolite.

2005, and Lavon and Benvenisty, 2005). , 2006). Each of the reports show the expression of early markers of hepatic differentiation as well as some more differentiated functions such as some limited drug ammonia metabolism or urea production. There are no reports of robust drug metabolism by any ES-derived hepatocyte-like cells. While quite preliminary, these initial results suggest that at least some of the ES cells are able to differentiate along a hepatic lineage. It is not entirely clear from the published work if differentiation is being directed by the experimental design or if spontaneous differentiation of ES cells is occurring in the cultures.

In addition to primary hepatocytes cultured in a sandwich configuration and stem cellderived hepatocytes, several recent developments in biological engineering and cellular biology have enabled a variety of new models for studying hepatotoxicity in vitro. Genetically engineered cells, as well as so called ‘three-dimensional (3-D) hepatocyte bioreactors’, have been established recently and are just now being applied to further our understanding of 24 Hepatotoxicity toxic events in the liver. In the case of engineered cells, these systems seek to provide a basis for more mechanistic insight into our current understanding of drug-induced hepatotoxicity, whereas the 3-D perfused models attempt to re-establish the in vivo microenvironment as well as build and improve upon some of the limitations of existing primary cell models.

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