ABSTRACT: Transcriptional analysis of organ-specific toxicity induced by a panPPAR agonist in mice: Identification of organ-specific toxicity biomarkers
Project description:Drug-induced liver injury (DILI) due to flucloxacillin is a rare but serious complication of treatment with this antimicrobial. The genetic basis of susceptibility is poorly understood as is the underlying molecular mechanism for disease. There is some evidence that flucloxacillin is a pregnane X receptor (PXR) agonist. The current study was concerned with investigating the relevance of PXR to flucloxacillin toxicity and with the identification of genes changing in expression in response to flucloxacillin.
Project description:In this study, we aim to identify candidate biomarkers which may be useful as surrogate indicators of toxicity for pre-clinical development of panPPAR-agonist drug candidates. Gene expression microarray, histopathology and clinical chemistry data were generated from liver, heart, kidney and skeletal muscles of three groups of mice administered with three different dosages of an experimental pan-peroxisome proliferator-activated receptor (pan-PPAR) agonist, PPM-201, for 14 days. The histopathology and clinical chemistry data were compared with the gene expression analysis and candidate biomarker genes were identified.
Project description:We used microarrays to detail the gene expression profile during WAT -beige transition by treatment of beta adrenergic receptor agonist . Stromal vascular fractions (SVF) from mice (n = 3/group) that received vehicle or beta3 adrenergic receptor agonist, CL, treatment were served for RNA extraction and hybridization on Affymetrix microarrays. We are trying to find out angiogenic factors genes dynamics during white adipose tissues (WAT) - beige transition.
