RESUMEN
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.
Asunto(s)
Antibacterianos/efectos adversos , Apoptosis/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Gentamicinas/efectos adversos , Riñón/efectos de los fármacos , Inhibidores de la Síntesis de la Proteína/efectos adversos , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/patología , Alternativas al Uso de Animales , Biomarcadores Farmacológicos/metabolismo , Línea Celular Transformada , Supervivencia Celular/efectos de los fármacos , Cistatina C/agonistas , Cistatina C/genética , Cistatina C/metabolismo , Evaluación Preclínica de Medicamentos/métodos , Factor de Crecimiento Epidérmico/antagonistas & inhibidores , Factor de Crecimiento Epidérmico/genética , Factor de Crecimiento Epidérmico/metabolismo , Citometría de Flujo , Perfilación de la Expresión Génica , Receptor Celular 1 del Virus de la Hepatitis A/agonistas , Receptor Celular 1 del Virus de la Hepatitis A/genética , Receptor Celular 1 del Virus de la Hepatitis A/metabolismo , Humanos , Concentración 50 Inhibidora , Interleucina-18/antagonistas & inhibidores , Interleucina-18/genética , Interleucina-18/metabolismo , Riñón/metabolismo , Riñón/patología , Túbulos Renales Proximales/efectos de los fármacos , Túbulos Renales Proximales/metabolismo , Túbulos Renales Proximales/patología , NecrosisRESUMEN
Drinking water treatment ultimately aims to provide safe and harmless drinking water. Therefore, the suitability of a treatment process should not only be assessed based on reducing the concentration os a pollutant concentration but, more importantly, on reducing its toxicity. Hence, the main objective of this study was to answer whether the degradation of a highly toxic compound of global concern for drinking water equals its detoxification. We, therefore, investigated the treatment of cylindrospermopsin (CYN) by â¢OH and SO4-⢠produced in Fenton and Fenton-like reactions. Although SO4-⢠radicals removed the toxin more effectively, both radical species substantially degraded CYN. The underlying degradation mechanisms were similar for both radical species and involved hydroxylation, dehydrogenation, decarboxylation, sulfate group removal, ring cleavage, and further fragmentation. The hydroxymethyl uracil and tricyclic guanidine moieties were the primary targets. Furthermore, the residual toxicity, assessed by a 3-dimensional human in vitro liver model, was substantially reduced during the treatment by both radical species. Although the results indicated that some of the formed degradation products might still be toxic, the overall reduction of the toxicity together with the proposed degradation pathways allowed us to conclude: "Yes, degradation of CYN equals its detoxification!".