API

Stressor: 50

Title

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Rotenone

Stressor Overview

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AOPs Including This Stressor

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Events Including This Stressor

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Chemical Table

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User term DTXID Preferred name Casrn jchem_inchi_key indigo_inchi_key
(2R,6aS,12aS)-1,2,6,6a,12,12a-hexahydro-2-isopropenyl-8,9-dimethoxychromeno[3,4-b]furo[2,3-h]chromen-6-one DTXSID6021248 Rotenone 83-79-4 JUVIOZPCNVVQFO-HBGVWJBISA-N JUVIOZPCNVVQFO-HBGVWJBISA-N

AOP Evidence

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Inhibition of the mitochondrial complex I of nigro-striatal neurons leads to parkinsonian motor deficits

The insecticide rotenone is a potent Inhibitor of complex I (CI) in the respiratory transport chain of mitochondroa with a relative selectivity for dopaminergig neurons in low dosage.Additional non-specific treatment related effects include: vascular damage with secondary ischemic neurodegeneration, tissue damage in heart and testicles and interstitial haemorrhages in lungs and kidneys. Mitochondrial dysfunction is considered to be the initial step in rotenone toxicity; though, multiple pathways are involved in the process associated with rotenone-induced neurotoxicity. however, the impact of rotenone on glial cells also impact on neuronal outcomes. (Aguilar et al.2015). Rotenone provided the first proof-of-concept that a systemic defect in mitochondrial function could lead to selective nigrostriatal neurodegeneration.  The rotenone animal model accurately recapitulates many other features of Parkinson's disease , including: accumulation and aggregation of endogenous, wildtype alpha-synuclein; α-synuclein- and polyubiquitin-positive Lewy bodies and Lewy neurites; apomorphine responsive behavioral deficits; early and sustained activation of microglia; oxidative modification and translocation of DJ-1 into mitochondria in vivo; impairment of the nigral ubiquitin-proteasome system; accumulation of iron in the substantia nigra through a mechanism involving transferrin and transferrin receptor 2; α-synuclein pathology in enteric neurons and functional deficits in GI function, including gastroparesis (Greenamyre et al. 2010). 




Event Evidence

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This table is automatically generated and includes the Events with this associated stressor as well as the evidence text from this Event Stressor.



Stressor Info

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Chemical/Category Description

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Characterization of Exposure

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References

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