Resumo

GALEANO, Antonia K.; CAMPUZANO-BUBLITZ, Miguel A.  e  KENNEDY, Maria Luisa. In vitro models used to predict drug hepatotoxicity in pre-clinical phase. Rev.Cs.Farm. y Bioq [online]. 2021, vol.9, n.2, pp.50-66.  Epub 30-Nov-2021. ISSN 2310-0265.  https://doi.org/10.53287/jsxf4577cu36l.

The liver is the main organ of the body whose function is to maintain internal homeostasis, it also plays a fundamental role in the metabolism of drugs (xenobiotics), therefore it is vulnerable to physiological or anatomical injuries. Drug-induced liver injury (DILI) is the most common cause of pre-clinical and clinical development failure of new drugs, black box warnings, and drug recall. Therefore, it represents a serious problem for the pharmaceutical industries, as well as for the patient, health professionals and regulatory entities. It should be mentioned that there are two types of drug-induced liver injury: pharmacological or intrinsic and idiosyncratic. During the pre-clinical stage of the drug development process, candidate drugs are screened using in vitro cell models that include 2D, 3D culture systems and human hepatoma cell lines, although other approaches use zebrafish (replacement for animal models), or cell models based on high content screening. Subsequently, animals are used, which despite having specific differences with respect to humans at the hepatocellular level are also used to make quantitative and qualitative predictions of the main pharmacodynamic, pharmacokinetic and toxicological properties of the candidate drug. Currently, there is a major effort to improve some existing in vitro models, coupling a tool or genetically modifying it towards the product of interest, providing new useful approaches for the potential prediction of liver toxicity, of the candidate drugs.

Palavras-chave : hepatotoxicity; pre-clinical; in vitro; cell lines..

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