Abstract:
:There are multiple lines of evidence showing that environmental toxicants including pesticides may contribute to neuronal cell death. Fipronil (FPN) is a phenylpyrazole insecticide that acts on insect GABA receptors. Although the action of FPN is restricted to insect neuronal or muscular transmitter systems, a few studies have assessed the effects of this neurotoxicant on neuronal cell death distinct from an insect. To determine the mechanisms underlying FPN-induced neuronal cell death, we evaluated the ability of this chemical to induce oxidative stress and studied the involvement of mitogen activated protein kinases (MAPKs) in FPN-induced apoptosis stress in human neuroblastoma SH-SY5Y (SH-SY5Y) cells. Exposure of SH-SY5Y cells to FPN led to the production of reactive oxygen species (ROS) and apoptotic cell death via activation of caspase-9 and caspase-3. Interestingly, the antioxidant, N-acetyl-cysteine (NAC) attenuated apoptotic cell death and ROS production induced by FPN. These results indicated that oxidative stress plays a central role in FPN-induced cytotoxicity. Mitochondrial complex I activity was also inhibited by FPN treatment. These finding indicate that FPN triggers intrinsic apoptosis via the mitochondrial signaling pathway that is initiated by the generation of ROS. Furthermore, FPN treatment induced phosphorylation of MAPK members. Activation of these protein kinases by FPN was involved in the onset of apoptosis as inhibitors specific to these kinases protect against FPN-induced cell death as well as ROS generation. Our data indicate that FPN-induced apoptosis is mediated primarily by the generation of ROS and activation of MAPK members followed by activation of the intrinsic apoptotic pathway.
journal_name
Toxicol Lettjournal_title
Toxicology lettersauthors
Ki YW,Lee JE,Park JH,Shin IC,Koh HCdoi
10.1016/j.toxlet.2012.02.022subject
Has Abstractpub_date
2012-05-20 00:00:00pages
18-28issue
1eissn
0378-4274issn
1879-3169pii
S0378-4274(12)00078-1journal_volume
211pub_type
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journal_title:Toxicology letters
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journal_title:Toxicology letters
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journal_title:Toxicology letters
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journal_title:Toxicology letters
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更新日期:2014-08-04 00:00:00
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journal_title:Toxicology letters
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更新日期:2018-03-01 00:00:00
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journal_title:Toxicology letters
pub_type: 杂志文章
doi:10.1016/j.toxlet.2008.10.022
更新日期:2009-01-10 00:00:00
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pub_type: 杂志文章,多中心研究
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journal_title:Toxicology letters
pub_type: 杂志文章,评审
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journal_title:Toxicology letters
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journal_title:Toxicology letters
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abstract::A number of zero tolerance provisions are contained in both food and animal feed law, e.g. for chemical substances whose occurrence is not permitted or is directly prohibited in food or animal feed. In the European Union, bans of this kind were introduced to give consumers and animals the greatest possible protection ...
journal_title:Toxicology letters
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更新日期:2007-12-10 00:00:00
abstract::Effects of sublethal concentration (0.8 of LC50 96 h) of nickel sulphate (NiSO4 X 7H2O) on muscle glycogen and blood lactic acid levels of a freshwater teleost, Colisa fasciatus, at time intervals from 3-96 h have been recorded. Muscle glycogen levels showed a general decrease at all time intervals compared with contr...
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pub_type: 杂志文章
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更新日期:1984-01-01 00:00:00