p-Aminophenol-induced cytotoxicity in Jurkat T cells: protective effect of 2(RS)-n-propylthiazolidine-4(R)-carboxylic acid.

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.