Antibiotic drug piperacillin induces neuron cell death through mitochondrial dysfunction and oxidative damage

Although nerve damage/toxicity has been shown to be one of the side effects in patients given prolonged antibiotic treatment, the mechanisms of the action of antibiotics on neuron cells are not clear. In this work, we investigated the toxicity of piperacillin (an antibiotic that can penetrate blood-brain barrier) on neuron cells and its underlying mechanisms. We show that clinically relevant doses of piperacillin induce apoptosis in SH-SY5Y and human primary neuron cells through activating caspase 3 activity and decreasing Mcl-1 and Bcl-2 levels. In addition, piperacillin causes mitochondrial dysfunction in neuron cells as shown by the reduction of mitochondrial respiration, membrane potential, and ATP production. We further demonstrate that piperacillin increases accumulation of mitochondrial superoxide and ROS, suggesting the oxidative stress in neuron cells. Consistently, oxidative damage to DNA, proteins, and membrane lipids are observed in neuron cells exposed to piperacillin. The deleterious effects...