Dihydrorotenone

Dihydrorotenone is an insecticide and irreversible inhibitor of mitochondrial complex I. Dihydrorotenone may induce Parkinson's disease. Dihydrorotenone induces apoptosis in human plasma cells by triggering endoplasmic reticulum stress and activating the p38 signaling pathway. The oral LD₅₀ of dihydrorotenone in rats is approximately 2.5 g/kg. Dihydrorotenone exhibits insecticide activity and cytotoxicity to plasma cells. Dihydrorotenone can be used to establish animal models of Parkinson's disease, safety assessment of natural pesticides, and potential cancer chemoprevention studies^[1][2][3][4]. In Vitro:Dihydrorotenone (20 μM; 24 h) induces apoptosis in human plasma cell lines LP1, OPM2, KMS11 and U266 in a concentration-dependent manner, activates caspase-3, -8, -9 and downregulates anti-apoptotic proteins Bcl-2 and Mcl-1^[1].
Dihydrorotenone (10 μM; 0.5 h or 24 h) causes mitochondrial membrane potential collapse in LP1 cells, and mitochondrial damage precedes apoptosis^[1].
Dihydrorotenone (40 μM; 24 h) induces endoplasmic reticulum stress in LP1 and OPM2 cells, upregulates GRP78, ATF4, CHOP and caspase-12, and activates the p38 MAPK signaling pathway^[1].
In Vivo:Dihydrorotenone ¹³C-labeled mitochondrial complex I can be used to label rat brain sections and in vivo, but incorporation is much lower in animals intoxicated with Rotenone (HY-B1756)^[2].
Dihydrorotenone (0.001-0.032% diet; oral; for approximately 400 days) causes dose-dependent growth retardation in female albino rats (weaning period), loss of hepatocyte basophilia and granular dispersion at concentrations of 0.004% and above, and no significant histological changes at concentrations of 0.001-0.002%^[3].