Genome-Scale Model-Based Identification of Metabolite Indicators for Early Detection of Kidney Toxicity.

ABSTRACT: Identifying early indicators of toxicant-induced organ damage is critical to provide effective treatment. To discover such indicators and the underlying mechanisms of toxicity, we used gentamicin as an exemplar kidney toxicant and performed systematic perturbation studies in Sprague Dawley rats. We obtained high-throughput data 7 and 13 h after administration of a single dose of gentamicin (0.5 g/kg) and identified global changes in genes in the liver and kidneys, metabolites in the plasma and urine, and absolute fluxes in central carbon metabolism. We used these measured changes in genes in the liver and kidney as constraints to a rat multitissue genome-scale metabolic network model to investigate the mechanism of gentamicin-induced kidney toxicity and identify metabolites associated with

SUBMITTER: Pannala VR 

PROVIDER: S-EPMC8000070 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature