{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T19:02:43Z","timestamp":1774292563080,"version":"3.50.1"},"reference-count":62,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2003,8]]},"abstract":"<jats:p>We have recently demonstrated the direct involvement of the death receptor-mediated apoptotic pathways in cisplatin-induced renal tubular cell (RTC) death. Reactive oxygen species are thought to be a major cause of cellular damage in such injury. The aim of this study was to examine the mechanism through which antioxidants ameliorate cisplatin-induced RTC death, with special emphasis on death receptor-mediated apoptotic pathways. Cisplatin was added to cultures of normal rat kidney (NRK52E) cells or injected in rats. NRK52E cells and rats were also treated with dimethylthiourea (DMTU), a hydroxyl radical scavenger. We then examined the mRNA levels of death ligands and receptors, caspase-8 activity, cell viability, cell death, renal function, and histological alterations. RT-PCR indicated cisplatin-induced upregulation of Fas, Fas ligand, and TNF-\u03b1 mRNAs and complete inhibition by DMTU in vitro and in vivo. Cisplatin increased caspase-8 activity of NRK52E cells, and DMTU prevented such activation. Exposure to cisplatin reduced viability of NRK52E cells, examined by WST-1 assay, and increased apoptosis and necrosis of the cells, examined by terminal deoxynucleotidyl transferase dUTP nick-end labeling assay and fluorescence-activated cell sorter analysis. DMTU abrogated cisplatin-induced changes in cell viability and apoptosis and\/or necrosis. Cisplatin-induced renal dysfunction and histological damage were also prevented by DMTU. DMTU did not hinder cisplatin incorporation into RTCs. Our results suggest that antioxidants can ameliorate cisplatin-induced acute renal failure through inactivation of the death receptor-mediated apoptotic pathways.<\/jats:p>","DOI":"10.1152\/ajprenal.00311.2002","type":"journal-article","created":{"date-parts":[[2015,3,3]],"date-time":"2015-03-03T20:38:35Z","timestamp":1425415115000},"page":"F208-F218","source":"Crossref","is-referenced-by-count":89,"title":["Antioxidant ameliorates cisplatin-induced renal tubular cell death through inhibition of death receptor-mediated pathways"],"prefix":"10.1152","volume":"285","author":[{"given":"Kazuhiko","family":"Tsuruya","sequence":"first","affiliation":[{"name":"Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan"}]},{"given":"Masanori","family":"Tokumoto","sequence":"additional","affiliation":[{"name":"Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, 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