title: p-Aminophenol-induced cytotoxicity in Jurkat T cells: protective effect of 2(RS)-n-propylthiazolidine-4(R)-carboxylic acid.
abstract: Acetaminophen (APAP) is hepatotoxic and can cause toxicity in Jurkat T cells. p-Aminophenol (PAP), an industrial chemical and APAP metabolite, is nephrotoxic and hepatotoxic. Its potential toxicity in Jurkat T cells was investigated. PAP (10-250 µM) caused toxicity (decreased survival and increased LDH activity in incubation medium) and GSH depletion. At a concentration of 100 µM but not 250 µM, PAP increased DNA fragmentation. It decreased p-Akt levels (Elisa) and at higher concentrations decreased p-Akt expression (Western blotting). It had no effect on FasL expression. The cysteine precursor 2(RS)-n-propylthiazolidine-4(R)-carboxylic acid (250 µM) attenuated the PAP (100 µM)-induced decrease in viability and prevented GSH depletion and increased DNA fragmentation. It attenuated the PAP-induced decrease in p-Akt levels and protected against the decrease in p-Akt expression. The results demonstrate PAP-induced toxicity and suggest that it is due at least in part to apoptosis and involves GSH depletion and p-Akt inactivation.
authors.affiliation: Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40292, USA.
authors.forename: Weiyuan
authors.initials: W
authors.lastname: Chang
authors.forename: Shrish
authors.initials: S
authors.lastname: Barve
authors.forename: Theresa S
authors.initials: TS
authors.lastname: Chen
mesh_terms: D000627:Aminophenols / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection; D004789:Enzyme Activation; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D016877:Oxidants / Q000633:toxicity*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology*
chemical_list: D000627:Aminophenols; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D016877:Oxidants; D013844:Thiazoles; C101197:2-n-propylthiazolidine-4-carboxylic acid; D051057:Proto-Oncogene Proteins c-akt; D005978:Glutathione; C026729:4-aminophenol