Aminoglycoside-induced lipotoxicity and its reversal in kidney on chip
Konstantinos Ioannidis, Aarón Cohen, Mohammad Ghosheh, Avner Ehrlich, Amit Fischer, Merav Cohen, Yaakov Nahmias
Abstract
, leading to a 3.2-fold increase in glucose uptake, and reverse TCA cycle flux culminating in a 40-fold increase in lipid accumulation. Blocking glucose reabsorption using the SGLT2 inhibitor empagliflozin significantly reduced gentamicin toxicity by 10-fold. These results demonstrate the utility of sensor-integrated kidney-on-chip platforms to rapidly identify new metabolic mechanisms that may underly adverse drug reactions. The results should improve our ability to modulate the toxicity of novel aminoglycosides.
Topics & Concepts
NephrotoxicityAminoglycosideGentamicinToxicityPharmacologyEmpagliflozinKidneyLipotoxicityChemistryDrugMedicineInternal medicineEndocrinologyDiabetes mellitusBiochemistryAntibioticsType 2 diabetesInsulin resistanceAntibiotics Pharmacokinetics and EfficacyMicrofluidic and Capillary Electrophoresis ApplicationsAnalytical Chemistry and Sensors