Enantioselective apoptosis and oxidative damage induced by individual isomers of profenofos in primary hippocampal neurons.
The purpose of this study was to investigate the apoptosis-related cytotoxic effects and molecular mechanisms of individual isomers of profenofos (PFF) on primary hippocampal neurons at 1.0 to 20 mg L-1. The cell viability and lactate dehydrogenase (LDH) efflux indicated that (-)-PFF exposure was associated with more toxic effects than (+)-PFF above the concentration of 5 mg L-1 (P < 0.5). Flow cytometric results showed that the percentages of apoptotic cells incubated with 20 mg L-1 (-)-PFF, (+)-PFF and rac-PFF for 24 h reached 23.4%, 9.2% and 14.2% (P < 0.01), respectively. Hippocampal neurons incubated with (-)-PFF, (+)-PFF and rac-PFF exhibited a dose-dependent accumulation of intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) and a dose-dependent inhibition of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activity, implying that the defense system of the tests induces oxidative damage. A statistically significant difference was observed between the two enantiomers at 5 mg L-1 and above. Moreover, the results showed that (-)-PFF exposure caused a significant loss in mitochondrial transmembrane potential (MMP), an upregulation of Ca2+ and Bax protein expression, a downregulation of Bcl-2 protein expression, and the activation of caspase-3 and caspase-9 in a dose-dependent manner; (+)-PFF and rac-PFF exhibited these effects to a lesser degree. All results suggest that PFF induced apoptosis in rat hippocampal neurons via the mitochondria-mediated pathway, and oxidative stress is one of the factors of PFF-induced apoptosis. In addition, (-)-PFF appears to play an important role in oxidative stress and apoptosis, indicating that enantioselectivity should be considered when assessing ecotoxicological effects and health risks of chiral pesticides.
['Lu|Xian T|XT|', 'Ma|Yun|Y|', 'Zhang|Hang J|HJ|', 'Jin|Mei Q|MQ|', 'Tang|Jun H|JH|']
D000818:Animals D017209:Apoptosis D020169:Caspases D002374:Catalase D002470:Cell Survival D006624:Hippocampus D007306:Insecticides D007770:L-Lactate Dehydrogenase D008315:Malondialdehyde D053078:Membrane Potential, Mitochondrial D009474:Neurons D063086:Organothiophosphates D018384:Oxidative Stress D017207:Rats, Sprague-Dawley D017382:Reactive Oxygen Species D013237:Stereoisomerism D013482:Superoxide Dismutase D051028:bcl-2-Associated X Protein
enantioselectivity Apoptosis profenofos oxidative stress mitochondrial pathway