抄録
Renal proximal tubule is the primary site for renal secretory elimination of drugs, toxins and their metabolites from the body. It is particularly susceptible to the damage by the toxicants. Cephaloridine, a first-generation of cephalosporin antibiotic, was known as nephrotoxicant transported into the renal proximal tubular cells by organic anion transporters (OATs). The mechanisms of nephrotoxicity induced by this compound have not yet completely understood. In this study, we examined the toxicity of low concentration of cephaloridine in OAT3-expressing renal proximal tubular cells (S2-OAT3) using cell viability assay. Transporter-mediated toxicity of cephaloridine was assessed at the molecular level using microarray analysis. The low concentration of cephaloridine and short exposure to the drug were used in this study to examine the early response of gene expression. The DNA microarray analysis revealed that the proliferative response and oxidative stress were involved in the toxicity process induced by cephaloridine. The transcription factors that participate in the regulation of functional changes were also predicted. This study would indicate an important direction of the genome wide analysis of transporter-mediated toxicity.
