INHIBITION OF THE RENAL UPTAKE OF P-AMINOHIPPURATE AND TETRAETHYLAMMONIUM BY THE ANTIOXIDANT ETHOXYQUIN IN THE RAT

Ethoxyquin (6-ethoxy-2,2,4-trimethyl-1,2-dihydroquinolein, EQ) is an a ntioxidant used in animal foodstuffs and to prevent superficial scaldi ng in some fruits. In renal cortical slices prepared from male rats th at had consumed a diet containing EQ, EQ inhibited the specific uptake of C-14-labelled p-aminohippurate ([C-14]PAH) and tetraethylammonium ([C-14]TEA), markers of organic anion and cation tubular secretion, re spectively. The specific uptake of [C-14]TEA was five-fold more sensit ive to EQ than [C-14]PAH uptake (IC50 0.33 and 1.51 mm, respectively). EQ (1 mM) decreased Na+/K+-ATPase activity from 1.58 to 1.0 mumol ino rganic phosphate/mg protein/min in renal microsomes. The activity of t his enzyme provides the energy for the function of both secretory syst ems. These results suggest that the mechanisms by which EQ inhibits bo th anion and cation tubular secretion involves a decrease in the Na+/K +-ATPase activity. This effect leads to interference with the energy s upply required for these tubular secretory mechanisms. Our results ind icate that the exposure of animals or humans to high concentrations of ethoxyquin should be avoided.