In vitro: Mitogen Activated Protein Kinase (MAPK), Toll-like receptor, Wnt, and Ras signaling pathways are intensively involved in the effect of rotenone on the ENS. Rotenone-induced cell death is reduced as measured by decline in the levels of pro-apoptotic proteins.
In vivo: Rotenone causes a significant increase in the excitatory amino acid neurotransmitters; glutamate and aspartate together with a significant decrease in the inhibitory amino acids, GABA, glycine and taurine are observed in the cerebellum of rat model of PD. Rotenone (1.5, 2, or 2.5 mg/kg) causes a dose-dependent increase in α-synuclein in the substantia nigra. Furthermore, at 2 and 2.5 mg/kg, rotenone causes a significant decrease in the number of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra, and dopamine in the striatum in rats.
|Cell lines||PC12 cells|
|Preparation method||For cell or brain tissue exposure, rotenone stock solutions were diluted with PBS to obtain a final solution of 1m DMSO. PC12 cells were exposed to rotenone or the corresponding solvent for different times.|
|Incubation time||48 h|
|Animal models||adult male Sprague–Dawley rats|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||10 mM in DMSO|
Metabolic enhancer piracetam attenuates rotenone induced oxidative stress: a study in different rat brain regions.
Verma DK, et al. Acta Neurobiol Exp. 2015;75(4):399-411. PMID: 26994419.
The molecular mechanism of rotenone-induced α-synuclein aggregation: emphasizing the role of the calcium/GSK3β pathway.
Yuan YH, et al. Toxicol Lett. 2015 Mar 4;233(2):163-71. PMID: 25433145.
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