title: In vitro and in vivo experimental hepatotoxic models in liver research: applications to the assessment of potential hepatoprotective drugs.
abstract: This mini-review highlights our and others' experience about in vitro and in vivo models that are being used to follow up events of liver injuries under various hepatotoxic agents and potential hepatoprotective drugs. Due to limitations of the outcomes in each model, we focus primarily on two models. First, a developed perfusion method for isolated immobilized hepatocytes that improves the process of oxygenation and helps in end-product removal is of considerable value in improving cell maintenance. This cellular model is presented as a short-term research-scale laboratory bioreactor with various physiological, biochemical, molecular, toxicological and pharmacological applications. Second, the in vivo model of D-galactosamine and lipopolysaccharide (D-GalN/LPS) combination-induced liver damage is described with some details. Recently, we have revealed that resveratrol and other natural polyphenols attenuate D-GalN/LPS-induced hepatitis. Moreover, we reported that D-GalN/LPS down-regulates sirtuin 1 in rat liver. Therefore, we discuss here the role of sirtuin 1 modulation in hepatoprotection. A successful development of pharmacotherapy for liver diseases depends on the suitability of in vitro and in vivo hepatic injury systems. Several models are available to screen the hepatotoxic or hepatoprotective activity of any substance. It is important to combine different methods for confirmation of the findings.
authors.affiliation: Institute of Pharmacology, First Faculty of Medicine, Charles University, Prague, Czech Republic. ncano@lf1.cuni.cz.
authors.forename: H
authors.initials: H
authors.lastname: Farghali
authors.forename: M
authors.initials: M
authors.lastname: Kgalalelo Kemelo
authors.forename: L
authors.initials: L
authors.lastname: Wojnarová
authors.forename: N
authors.initials: N
authors.lastname: Kutinová Canová
mesh_terms: D000818:Animals; D035843:Biomedical Research / Q000379:methods*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D055808:Drug Discovery / Q000379:methods*; D005688:Galactosamine / Q000633:toxicity; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity; D017114:Liver Failure, Acute / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control*; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D008070:Lipopolysaccharides; D020011:Protective Agents; D013267:Stilbenes; D005688:Galactosamine; D056564:Sirtuin 1; D000077185:Resveratrol