Cytotoxicity of 2-tert-butyl hydroquinone glutathione conjugates after apical and basolateral exposure of rat renal proximal tubular cell monolayers

Toxicology in Vitro : an International Journal Published in Association with BIBRA
H E HaenenP J van Bladeren

Abstract

Confluent monolayers of renal proximal tubular (RPT) cells cultured on porous supports were used to investigate the cytotoxicity induced by glutathione conjugates of 2-tert-butyl-(1,4)-hydroquinone (SG-TBHQ) after apical and basolateral exposure. As judged from lactate dehydrogenase (LDH) leakage, cytotoxicity was observed after basolateral exposure of monolayers to 250 and 500 mum 2-tert-butyl-5-(glutathion-S-yl)hydroquinone (5SG-TBHQ). In these experiments, LDH leakage was 22.3 +/- 1.9 and 32.2 +/- 1.9%, respectively. Basolateral exposure of monolayers to 250 and 500 mum 6SG-TBHQ resulted in LDH leakage of 22.2 +/- 2.5 and 30.0 +/- 2.7%, respectively. The double conjugate, 2-tert-butyl-3,6-(diglutathione-S-yl)hydroquinone (3,6SG-TBHQ), was not toxic and LDH leakage was about control level (15.0%). Basolaterally located probenecid-sensitive organic anion transporters did not seem to play a part in the cytotoxic effect. However, when RPT cell monolayers were cultured in 24-well tissue culture plates, apical challenge with 250 mum 5SG-TBHQ induced a cytotoxic effect. In these experiments, LDH leakage was 33.5 +/- 0.6%. With these cells, inhibition of apical gamma-glutamyltranspeptidase (gammaGT) activity by acivicin, which was n...Continue Reading

References

Jan 1, 1992·Critical Reviews in Toxicology·T J Monks, S S Lau
Jan 1, 1991·Chemico-biological Interactions·H VerhagenJ C Kleinjans
Jan 1, 1986·Toxicologic Pathology·J Ishmael, E A Lock
Oct 1, 1983·Biopharmaceutics & Drug Disposition·R El-Rashidy, S Niazi
Jan 1, 1996·Chemical Research in Toxicology·M M PetersT J Monks
Apr 1, 1994·Toxicology in Vitro : an International Journal Published in Association with BIBRA·H E HaenenP J van Bladeren

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Citations

May 10, 2012·Indian Journal of Ophthalmology·Ashish SharmaCristina M Kenney

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