Rotenone-induced oxidative stress in THP-1 cells: biphasic effects of baicalin

Background Several results demonstrated that microglia and peripheral monocytes/macrophages infiltrating the central nervous system (CNS) are involved in cell response against toxic compounds. It has been shown that rotenone induces neurodegeneration in various in vitro experimental models. Baicalin, a natural compound, is able to attenuate cell damage through anti-oxidant, anti-microbial, anti-inflammatory, and immunomodulatory action. Using THP-1 monocytes, we investigated rotenone effects on mitochondrial dysfunction and apoptosis, as well as baicalin ability to counteract rotenone toxicity. Methods and results THP-1 cells were exposed to rotenone (250 nM), in the presence/absence of baicalin (10-500 mu M) for 2-24 h. Reactive Oxygen Species production (ROS), mitochondrial activity and transmembrane potential (Delta psi m), DNA damage, and caspase-3 activity were assessed. Moreover, gene expression of mitochondrial transcription factor a (mtTFA), interleukin-1 beta (IL-1 beta), B-cell lymphoma 2 (Bcl2) and BCL2-associated X protein (Bax), together with apoptotic morphological changes, were evaluated. After 2 h of rotenone incubation, increased ROS production and altered Delta psi m were observed, hours later resulting in DNA oxidative damage and apoptosis. Baicalin treatment at 50 mu M counteracted rotenone toxicity by modulating the expression levels of some proteins involved in mitochondrial biogenesis and apoptosis. Interestingly, at higher baicalin concentrations, rotenone-induced alterations persisted. Conclusions These results give evidence that exposure to rotenone may promote the activation of THP-1 monocytes contributing to enhanced neurodegeneration. In this context, baicalin at low concentration exerts beneficial effects on mitochondrial function, and thus may prevent the onset of neurotoxic processes.