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 antioxidant used in animal foodstuffs and to prevent superficial scalding in some fruits. In renal cortical slices prepared from male rats that had consumed a diet containing EQ, EQ inhibited the specific uptake of ¹⁴C-labelled p-aminohippurate ([¹⁴C]PAH) and tetraethylammonium ([¹⁴C]TEA), markers of organic anion and cation tubular secretion, respectively. The specific uptake of [¹⁴C]TEA was five-fold more sensitive to EQ than [¹⁴C]PAH uptake (IC₅₀ 0.33 and 1.51 mm, respectively). EQ (1 mm) decreased Na⁺/K⁺-ATPase activity from 1.58 to 1.0 μmol inorganic phosphate/mg protein/min in renal musomes. The activity of this enzyme provides the energy for the function of both secretory systems. These results suggest that the mechanisms by which EQ inhibits both anion and cation tubular secretion involves a decrease in the Na^-/K⁺-ATPase activity. This effect leads to interference with the energy supply required for these tubular secretory mechanisms. Our results indicate that the exposure of animals or humans to high concentrations of ethoxyquin should be avoided.