Cytotoxicity of 2-tert-butyl hydroquinone glutathione conjugates after apical and basolateral exposure of rat renal proximal tubular cell monolayers
| العنوان: | Cytotoxicity of 2-tert-butyl hydroquinone glutathione conjugates after apical and basolateral exposure of rat renal proximal tubular cell monolayers |
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| المؤلفون: | H.E.M.G. Haenen, J.H.M. Temmink, E. Bleijlevens, P.J. van Bladeren, Jan H. Koeman, H. Elzerman |
| المساهمون: | Instituut CIVO-Toxicologie en Voeding TNO |
| المصدر: | Toxicology in Vitro, 2, 10, 141-148 Toxicology in Vitro 10 (1996) Toxicology in Vitro, 10, 141-148 |
| سنة النشر: | 1996 |
| مصطلحات موضوعية: | tert-Butylhydroquinone, Organic anion transporter 1, biology, Chemistry, General Medicine, Glutathione, Ascorbic acid, Toxicology, Superoxide dismutase, chemistry.chemical_compound, Biochemistry, Lactate dehydrogenase, biology.protein, Life Science, Cytotoxicity, Acivicin, Toxicologie |
| الوصف: | 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 μM 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 μM 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 μM 5SG-TBHQ induced a cytotoxic effect. In these experiments, LDH leakage was 33.5 ± 0.6%. With these cells, inhibition of apical γ-glutamyltranspeptidase (γGT) activity by acivicin, which was not toxic by itself, decreased 5SG-TBHQ-induced LDH leakage to 19.3 ± 1.2%, whereas 6SG-TBHQ (also 250 μM)-induced LDH leakage was increased to 55.3 ± 1.0%. Co-incubation of RPT cells with SG-TBHQs in the presence of 1.5 mM ascorbic acid (AA) pointed to a pro-oxidant rather than an antioxidant effect of AA. Superoxide dismutase and catalase completely abolished SG-TBHQ-induced cytotoxicity. Since cultured RPT cells lack N-acetylation of cysteine conjugates, the N-deacetylation/N-acetylation ratio cannot have a vital role in renal toxicity of quinone thioethers in this in vitro system. It seems, therefore, that the cytotoxicity observed is mainly the result of extracellular redox cycling of SG-TBHQs. The lack of toxicity of 6SG-TBHQ after apical exposure could be due to detoxification by γGT-mediated cysteinylglycine- or cysteine-conjugate formation followed by cyclization, as shown for other related quinone glutathione conjugates. The relative importance of the observed effects for the in vivo situation is discussed. Chemicals/CAS: acivicin, 42228-92-2; ascorbic acid, 134-03-2, 15421-15-5, 50-81-7; catalase, 9001-05-2; lactate dehydrogenase, 9001-60-9; superoxide dismutase, 37294-21-6, 9016-01-7, 9054-89-1; tert butylhydroquinone, 1948-33-0 |
| وصف الملف: | application/pdf; application/octet-stream |
| اللغة: | English |
| تدمد: | 0887-2333 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9089ea425adf17166a4441a2d2e51953Test https://doi.org/10.1016/0887-2333Test(95)00116-6 |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....9089ea425adf17166a4441a2d2e51953 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 08872333 |
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