Abstract
Central nervous system oxygen toxicity (CNS-OT) is a complication of hyperbaric oxygen (HBO) treatment, with limited prevention and treatment options available. In this study, we aimed to explore the effect of polyethylene glycol 300 (PEG300) on CNS-OT and underlying mechanisms. Motor and cognitive functions of mice in normobaric conditions were evaluated by Morris water maze, passive active avoidance, and rotarod tests. HBO was applied at 6 atmospheres absolute (ATA) for 30 min after drug administration. The latency period of convulsion in mice was recorded, and hippocampal tissues were extracted for biochemical experiments. Our experimental results showed that PEG300 extended the convulsion latencies in CNS-OT mice, reduced oxidative stress and inflammation levels in hippocampal tissues. Furthermore, PEG300 preserved mitochondrial integrity and maintained mitochondrial membrane potential in hippocampal tissue by upregulating Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha (PGC-1α). This protective effect was enhanced following the administration of ZLN005, an agonist of PGC-1a. Hence, our study suggests that PEG300 might exert protective effects by upregulating PGC-1α expression and preserving mitochondrial health, offering promising prospects for CNS-OT treatment.
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Funding
This study was supported by the National Natural Science Foundation of China (Grant numbers 82171867), the Science and Technology Commission of Shanghai Municipality (Grant numbers 21ZR1478300), and the Naval Medical University Natural Science Incubation Fund (Grant numbers 2023MS025).
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The study conception and design were contributed by Jiao Qian and Jun Yang. Material preparation were performed by **n Li, Yue Shen and Dan Li ,the experiments were carried out by **n Li, Kun Zhang and Yue Shen. data collection and analysis were performed by Kun Zhang, Jia Liu and Lu Yao. The first draft of the manuscript was written by **n Li and Jiao Qian, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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Li, X., Shen, Y., Li, D. et al. PEG300 Protects Mitochondrial Function By Upregulating PGC-1α to Delay Central Nervous System Oxygen Toxicity in Mice. Neurotox Res 42, 30 (2024). https://doi.org/10.1007/s12640-024-00708-0
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DOI: https://doi.org/10.1007/s12640-024-00708-0