Effect of acetaminophen on Na+, K+ ATPase and alkaline phosphatase en plasma membranes of renal proximal tubules

TRUMPER, L.; GABRIELA COUX; ELIAS, M. M.

Toxicology and Applied Pharmacology

Academic Press

Año: 2000 vol. 164 p. 143 - 148

In previous work we reported that 1 h after acetaminophen(APAP) administration, tubular function remained at control values,while 16 h later a significant deterioration of tubular functionwas observed. The aim of the present work was to study if APAPinduces its renal toxic effects by altering the normal activity of keytubular plasma membrane enzymes. We analyzed the effects of anephrotoxic dose of APAP (1000 mg/kg b.wt., i.p.) on the activitiesof the brush-border membrane (BBM) enzyme, alkaline phosphatase,and the basolateral membrane (BLM) enzyme Na1, K1ATPase 1 h (APAP1h) and 16 h (APAP16h) after dosing. Na1, K1ATPase abundance in homogenates and each membrane domainwere analyzed by Western blot. Cortical adenosine 5* triphosphate(ATP) content was also evaluated. At each time studied, APAPpromoted a diminution of alkaline phosphatase in BBM. Na1, K1ATPase activity in BLM showed a biphasic response to APAP. Onehour after APAP administration it was significantly increased, butit was decreased 16 h after dosing. Na1, K1 ATPase proteinabundance was elevated in homogenates, BLM, and BBM after 1 hof APAP dosing. After 16 h, Na1, K1 ATPase abundance wasincreased in homogenates, while in BLM it was decreased. Nodifferences were observed in cortical ATP content in each timestudied. Our present results could contribute to the understandingof the molecular basis of the previously reported time coursealteration in the fractional excretion of sodium promoted by anephrotoxic dose of APAP.