In vitro and in vivo effects of chlorpyrifos on glutathione peroxidase and catalase in developing rat brain.
Preliminary findings of a study on the role of oxidative stress in the developmental neurotoxicity of chlorpyrifos (CPF) indicates that in vitro exposure to 1-100 microM CPF or 1-100 nM CPF-oxon had no effect on the activity of glutathione peroxidase (GSHpx) in brain homogenates from postnatal day (PN) 21 rats, or on the activity of purified GSHpx. A single high-dose acute injection of 45 mg/kg CPF to PN19 rats also did not significantly alter GSHpx activity at PN21, in spite of extensive (72%) brain acetylcholinesterase (AChE) inhibition. However, catalase activity was significantly reduced by 28%. PN21 pups exposed maternally to a lower effective dose of CPF throughout development (dams injected with 50 mg/kg every 3 days) also had normal GSHpx activity, but a 30% increase in H2O2-independent NADPH consumption. Brain catalase activity in these rats was significantly increased by 24%. These preliminary data suggest that specific GSHpx activity is not altered by in vitro or in vivo exposures to CPF-oxon or CPF, but catalase and an unknown H2O2-independent NADPH-consuming factor were affected differentially depending on the type and timing of exposure.
Jett
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DA
Department of Environmental Health Sciences, The Johns Hopkins University School of Hygiene and Public Health, Baltimore, MD 21205, USA. djett@jhsph.edu
Navoa
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RV
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development*; D002374:Catalase / Q000378:metabolism*; D004390:Chlorpyrifos / Q000031:analogs & derivatives / Q000633:toxicity*; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D007306:Insecticides / Q000633:toxicity*; D009249:NADP / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D020318:Rats, Long-Evans
D007306:Insecticides; D009249:NADP; C009618:O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphate; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; D000110:Acetylcholinesterase; D004390:Chlorpyrifos