title: Sub-nephrotoxic doses of gentamicin predispose animals to developing acute kidney injury and to excrete ganglioside M2 activator protein.
abstract: We studied whether nephrotoxic drug administration sensitizes to acute renal failure (ARF) by administering a sub-nephrotoxic dose of gentamicin. This pre-treatment sensitized animals with no sign of renal injury to develop ARF when exposed to a second potential nephrotoxic drug, also given at sub-nephrotoxic doses that would be otherwise harmless to non-sensitized animals. We identified urinary ganglioside M2 activator protein (GM2AP) as a biomarker of an enhanced sensitivity to suffer ARF following sub-nephrotoxic treatment with gentamicin. Sub-nephrotoxic gentamicin did not alter renal GM2AP gene expression or protein levels, determined by reverse transcriptase-PCR, western blot, and immunostaining, nor was its serum level modified. The origin of increased GM2AP in the urine is thought to be a defective tubular handling of this protein as a consequence of gentamicin action. Hence, markers of acquired sensitivity may improve the prevention of ARF by enhancing our capacity to monitor for this condition, in a preemptive manner.
authors: Unidad de Fisiopatología Renal y Cardiovascular, Departamento de Fisiología y Farmacología, Universidad de Salamanca, Salamanca, Spain.
authors: Yaremi
authors: Y
authors: Quiros
authors: Laura
authors: L
authors: Ferreira
authors: Sandra M
authors: SM
authors: Sancho-Martínez
authors: José M
authors: JM
authors: González-Buitrago
authors: José M
authors: JM
authors: López-Novoa
authors: Francisco J
authors: FJ
authors: López-Hernández
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000175:diagnosis / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005732:Gangliosides / Q000378:metabolism*; D005839:Gentamicins / Q000009:adverse effects*; D011500:Protein Synthesis Inhibitors / Q000009:adverse effects; D051381:Rats; D017208:Rats, Wistar; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D005732:Gangliosides; D005839:Gentamicins; D011500:Protein Synthesis Inhibitors