D-beta-hydroxybutyrate prevents MPP+-induced neurotoxicity in PC12 cells.

Numerous studies show that D-beta-Hydroxybutyrate (DbetaHB) is neuroprotective. The present study was to explore the neuroprotective effects of DbetaHB against the cell death and apoptosis induced by 1-methyl-4-phenylpyridinium ion (MPP+) in PC12 cells. PC12 cells were pretreated with DbetaHB and followed by MPP+ exposure. The cell viability was determined by MTT assay. The morphological characteristics of apoptosis was observed by Acridine Orange (AO) staining and apoptotic rates were measured by flow cytometer. The product of lipid peroxidation, malondialdehyde (MDA), was measured using thiobarbituric acid method. The mitochondrial membrane potential (MMP), intracellular ROS and total glutathione were detected by microplate reader. In PC12 cells, pretreatment with DbetaHB significantly reduced MPP+-induced the decrease of cell viability. AO staining and flow cytometric analysis found DbetaHB inhibited MPP+-induced apoptosis. The measurement of MDA formation showed that DbetaHB alleviated lipid peroxidation induced by MPP+. The loss of MMP induced by MPP+ was preventive by DbetaHB. The changes of intracellular ROS and total glutathione induced by MPP+ were reversed by DbetaHB. DbetaHB protected PC12 cells against MPP+-induced death and apoptosis.