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pubmed-article:11162874pubmed:abstractTextThe present studies were designed to investigate the susceptibility of LLC-PK1 cells to cytotoxicity induced by para-aminophenol (PAP) and the ability of antioxidants to prevent PAP-induced cytotoxicity. LLC-PK1 cells were incubated for 4 h with varying concentrations of PAP (0-0.2 mM). Incubation was continued for 20 h and viability was monitored at 24 h after initial exposure to PAP. For coincubation experiments, cells were incubated for 4 h with various antioxidants [including ascorbate, glutathione (GSH), butylated hydroxytoluene (BHT), beta-nicotinamide adenine dinucleotide (NADH), or beta-nicotinamide adenine dinucleotide phosphate (NADPH)] in the absence or presence of 0.1 mM PAP. For preincubation experiments, cells were incubated for 1 h with ascorbate, GSH or NADPH. Antioxidants were removed and cells were exposed to 0 or 0.1 mM PAP for 4 h. Viability was determined 24 h following PAP exposure. LLC-PK1 cells displayed a steep concentration-response relationship for PAP; 0.1 mM PAP caused approximately 50% loss of viability. Coincubation with ascorbate, GSH and NADPH was without effect on cell viability in the absence of PAP and attenuated PAP-induced losses in viability. In contrast, NADH was ineffective in preventing PAP-induced cytotoxicity. BHT alone produced a significant loss of cell viability and was ineffective in preventing PAP cytotoxicity. Inability of NADH to prevent PAP-induced cytotoxicity was related to rapid degradation of NADH in aqueous solution. Preincubation of cells with ascorbate or GSH but not NADPH was associated with attenuation of PAP-induced cytotoxicity. These data suggest that (1) PAP is cytotoxic to LLC-PK1 cells, (2) a portion of PAP cytotoxicity is due to nonenzymatic oxidation that occurs in the incubation medium, and (3) a portion of PAP cytotoxicity is due to enzymatic or nonenzymatic oxidation that occurs within cells.lld:pubmed
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pubmed-article:11162874pubmed:authorpubmed-author:TarloffJ BJBlld:pubmed
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pubmed-article:11162874pubmed:pagination37-45lld:pubmed
pubmed-article:11162874pubmed:dateRevised2007-11-14lld:pubmed
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pubmed-article:11162874pubmed:articleTitleEffect of antioxidants on para-aminophenol-induced toxicity in LLC-PK1 cells.lld:pubmed
pubmed-article:11162874pubmed:affiliationDepartment of Pharmaceutical Sciences, University of the Science in Philadelphia, 600 South 43rd Street, Philadelphia, PA 19104-4495, USA.lld:pubmed
pubmed-article:11162874pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:11162874pubmed:publicationTypeResearch Support, U.S. Gov't, P.H.S.lld:pubmed
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