Description
Rotenone is a pesticide that exhibits genotoxic, pro-oxidative, and neurodegenerative properties. In vitro, rotenone induces formation of micronuclei and modifies the microtubule organizing centers of mitotic spindles. In other cellular models, rotenone inhibits the mitochondrial electron transport complex I, altering mitochondrial respiration and inducing mitochondrial oxidative stress. Rotenone also inhibits background K+ currents, causing rapid cell membrane depolarization and increases in intracellular Ca2+. In vitro, this compound also activates microglial superoxide release, resulting in neurodegeneration of dopaminergic neurons, mimicking pathologies associated with Parkinson’s disease.
References
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Sherer TB, Richardson JR, Testa CM, et al. Mechanism of toxicity of pesticides acting at complex I: relevance to environmental etiologies of Parkinson's disease. J Neurochem. 2007 Mar;100(6):1469-79. PMID: 17241123.
Wyatt CN, Buckler KJ. The effect of mitochondrial inhibitors on membrane currents in isolated neonatal rat carotid body type I cells. J Physiol. 2004 Apr 1;556(Pt 1):175-91. PMID: 14724184.
Gao HM, Hong JS, Zhang W, et al. Distinct role for microglia in rotenone-induced degeneration of dopaminergic neurons. J Neurosci. 2002 Feb 1;22(3):782-90. PMID: 11826108.
