Expression profiles from kidneys of rats treated with nephrotoxicants and with controls

The objective of the study described here was to discover a genetic biomarker signature that can predict the occurrence of drug-induced renal toxicity before it is detected by clinical chemistry examination or histopathology. In order to identify the biomarker signature, Sprague-Dawley Crl:CD(SD) rats were treated with well-known renal toxins: Gentamicin, Cisplatin, Tobramycin, Cadmium Chloride, and Doxorubicin, and with controls - valproic acid, and saline. The substances were administrated daily for 1, 5 or 28 days at doses that are expected to induce kidney-specific histopathological and clinical chemistry changes not before 28 days of repetitive dosing. At the end of treatment, kidneys from the treated animals were removed; the RNA from these kidneys, and from kidneys of several naive animals was extracted and subjected to microarray expression analysis. Twenty candidate genes which showed significant changes from control were identified using microarray experiments. Rats were treated with 7 different compounds - 5 known nephrotoxicants and 2 controls. Each compound was administrated daily for 1,5 and 28 days. The microarray expereiments were done for the 1 and 5-days groups, and for an additional control group of naive (untreated) rats. Each group contained 3 males and 3 females. Half of the apical parts of each kidney of each animal was taken, and the two halves were homogenized prior to RNA extraction