Sub-nephrotoxic doses of gentamicin predispose animals to developing acute kidney injury and to excrete ganglioside M2 activator protein.
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.
Quiros
Yaremi
Y
Unidad de Fisiopatología Renal y Cardiovascular, Departamento de Fisiología y Farmacología, Universidad de Salamanca, Salamanca, Spain.
Ferreira
Laura
L
Sancho-Martínez
Sandra M
SM
González-Buitrago
José M
JM
López-Novoa
José M
JM
López-Hernández
Francisco J
FJ
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
D015415:Biomarkers; D005732:Gangliosides; D005839:Gentamicins; D011500:Protein Synthesis Inhibitors