| 20020887 |
Geter DR, Kan HL, Lowe ER, Rick DL, Charles GD, Gollapudi BB, Mattsson JL: Investigations of oxidative stress, antioxidant response, and protein binding in chlorpyrifos exposed rat neuronal PC12 cells. Toxicol Mech Methods. 2008;18(1):17-23.
ABSTRACT Chlorpyrifos (CPF) is a widely used organophosphate insecticide. In addition to its known properties of cholinesterase inhibition, the production of reactive oxygen species (ROS) has been suggested as a possible toxic mechanism. To investigate CPF-generated ROS, rat neuronal PC12 cells were exposed to CPF concentrations of 0 to 5000 mug/mL in Krebs buffered media (KRH), KRH + 4% bovine serum albumin (BSA), and KRH + 25 muM of the antioxidant Trolox for 0 to 5 h. Paraquat served as a positive control for ROS. The fluorescent probe 2,7-dichlorodihydro-fluorescein and the MTS assay were used to measure ROS and cytotoxicity, respectively. Examinations into CPF-albumin binding were also conducted. CPF was not strongly cytotoxic to PC12 cells, causing only mild cytotoxicity at 5000 mug/ml. In KRH media, CPF-generated ROS was observed at 4 and 5 h at 500 and 1000 mug/mL, and at 1 to 5 h at 5000 mug/mL CPF. In KRH + 4% BSA, ROS was seen only at 5 h in 5000 mug/mL CPF. Trolox significantly reduced CPF- and paraquat-induced ROS. Calculated CPF-albumin binding at 1, 10, and 100 mug/mL CPF in 4% BSA was 96%, 75%, and 15%. These data show CPF at >/=500 mug/mL induced ROS in PC12 cells, but the addition of the antioxidant Trolox and 4% BSA dramatically reduced ROS levels. |
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