Electron Microscope Unit, Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand.
Department of Physiology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand.
Neurotox Res. 2020 Feb;37(2):455-468. doi: 10.1007/s12640-019-00090-2. Epub 2019 Jul 30.
Several studies have recently revealed that cognitive function can be affected by paracetamol (APAP) treatment. However, the exact impact of this drug treatment on learning and memory has not been clarified. This study aimed to investigate the effect of APAP treatment on the alteration of synapses and oxidative stress in the rat frontal cortex and hippocampus. APAP at a dose of 200 mg/kg bw was fed to adult male Wistar rats through either acute (n = 10), 15-day (n = 10), or 30-day (n = 10) treatment regimens. The synaptic ultrastructure and proteins, synaptophysin (SYP) and postsynaptic density-95 (PSD-95), were monitored. The amount of protein carbonyl oxidation (PCO) and glutathione (GSH) levels were examined. Our results demonstrated that acute treatment with APAP had no effect on synapses and oxidative stress. However, the synapses obtained from rats with 15-day APAP treatment showed a marked shortening of active zones and widening of the synaptic cleft. Decrement of SYP and PSD-95 proteins were demonstrated in these rats as well. With 30-day APAP treatment, the alteration of the synaptic ultrastructure and proteins was more evident. Moreover, the depletion of GSH and the elevation of PCO levels were demonstrated in the rats treated with APAP for 30 days. These results suggest that long-term APAP treatment can induce synaptic degeneration in the hippocampus and frontal cortex. The increase in oxidative stress in these brain areas may be due to the deleterious effect of this drug.
最近的几项研究表明，对乙酰氨基酚（APAP）治疗会影响认知功能。然而，这种药物治疗对学习和记忆的确切影响尚未阐明。本研究旨在探讨 APAP 治疗对大鼠前额叶皮质和海马突触和氧化应激改变的影响。APAP 以 200mg/kg bw 的剂量通过急性（n = 10）、15 天（n = 10）或 30 天（n = 10）治疗方案喂食成年雄性 Wistar 大鼠。监测突触超微结构和蛋白质，突触小泡蛋白（SYP）和突触后密度蛋白-95（PSD-95）。检查蛋白质羰基氧化（PCO）和谷胱甘肽（GSH）水平的量。我们的结果表明，APAP 的急性治疗对突触和氧化应激没有影响。然而，来自接受 15 天 APAP 治疗的大鼠的突触显示出活跃区域明显缩短和突触间隙变宽。这些大鼠的 SYP 和 PSD-95 蛋白也减少了。经过 30 天 APAP 治疗，突触超微结构和蛋白质的改变更为明显。此外，在接受 30 天 APAP 治疗的大鼠中，GSH 的耗竭和 PCO 水平的升高被证明。这些结果表明，长期 APAP 治疗会导致海马体和前额叶皮质中的突触退化。这些大脑区域的氧化应激增加可能是由于这种药物的有害作用。
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