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 vivomodel 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.
The present review is intended to focus on naturally occurring cytoprotective agents such as resveratrol (trans-3,4’,5- trihydroxystilbene) and other related compounds, probably with similar molecular mechanisms of action and high capacity to find applications in medical fields. Several physiological aspects have been ascribed to resveratrol and similar compounds. Resveratrol, among others, has been recently described as a silent information regulator T1 (SIRT1) activator that increases AMPactivated protein kinase (AMPK) phosphorylation and reduces the oxidative damage biomarkers during aging in laboratory settings. The reports on resveratrol and other SIRT1 activators from various sources are encouraging. The pharmacological strategies for modulation of sirtuins by small molecules through allosteric mechanisms should gain a greater momentum including human research. Resveratrol and resveratrol-like molecules seem to fulfill the requirement of a new horizon in drug research since these molecules cover a growing research means as antioxidants with allosteric mechanism in epigenetic drug targets. However, one should keep in mind the challenges of extrapolation of basic research into clinical results. Overall, the issue of sirtuins in biology and disease provides an insight on therapeutic potentials of sirtuin-based therapeutics and demonstrates the high complexity of drug-targeting these modalities for human applications., H. Farghali, N. Kutinová Canová, N. Lekić., and Obsahuje seznam literatury