Journal of biochemical and molecular toxicology · 2018
In vitro evaluation of biomarkers of nephrotoxicity through gene expression using gentamicin.
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Campos Maria A A, de Almeida Leonardo A, Grossi Marina F, Tagliati Carlos A
Аннотация
Acute renal failure is one of the most frequent effects observed after taking medicine. Such situations have been tardily discovered, given that existing methods for assessing toxicity are not predictive. In this light, the present work evaluated the effects of gentamicin, a form of nephrotoxic drug, on HK-2 and HEK-293 cells. By using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and flow cytometry, both cells demonstrated that cytotoxicity occurs in a dose-dependent manner through the processes of apoptosis and cell necrosis. Gene expression analysis showed a relative increase of expression for genes related to cell processes and classic biomarkers, such as TP53, CASP3, CASP8, CASP9, ICAM-1, EXOC3, KIM-1, and CST3. A decrease in expression for genes BCL2L1 and EGF was observed. This study, therefore, indicates that, when the methods are used together, gene expression analysis is able to evaluate the nephrotoxic potential of a substance.
Предметные рубрики MeSH
Acute Kidney InjuryAnimal Use AlternativesAnti-Bacterial AgentsApoptosisBiomarkers, PharmacologicalCell Line, TransformedCell SurvivalCystatin CDrug Evaluation, PreclinicalEpidermal Growth FactorFlow CytometryGene Expression ProfilingGene Expression RegulationGentamicinsHepatitis A Virus Cellular Receptor 1HumansInhibitory Concentration 50Interleukin-18KidneyKidney Tubules, ProximalNecrosisProtein Synthesis Inhibitors