Nephrotoxicity and transport of celiptium in rabbit renal proximal tubule suspensions

The antitumor drug N2-methyl-9-hydroxyellipticinium (celiptium) is a cationic ellipticine derivative that is particularly active against renal and breast cancer. Celiptium uptake and cytotoxicity were examined utilizing isolated rabbit renal proximal tubules in suspension. in tubule suspensions, celiptium showed dose- and time-dependent cytotoxicity as evidenced by increased release of lactate dehydrogenase (LDH) and loss of intracellular potassium ion (K⁺) content. Celiptium at 100 μM reduced the uptake of the organic cation, tetraethylammonium (T:M ratio, 4) compared to controls (T:M ratio, 20) in proximal tubules as early as 15 min and this was sustained over a 4-h period. There was no effect on uptake of the organic anion, p-aminohippurate. These studies suggest that celiptium is cytotoxic to isolated rabbit proximal tubule suspensions and that it may be transported into the tubule cell by the organic cation system.