2. Academic Validation
  3. PEG300 Protects Mitochondrial Function By Upregulating PGC-1α to Delay Central Nervous System Oxygen Toxicity in Mice

PEG300 Protects Mitochondrial Function By Upregulating PGC-1α to Delay Central Nervous System Oxygen Toxicity in Mice

  • Neurotox Res. 2024 Jun 17;42(4):30. doi: 10.1007/s12640-024-00708-0.
Xin Li # 1,  Yue Shen # 1,  Dan Li # 2,  Kun Zhang 3,  Jia Liu 4,  Lu Yao 5,  Jun Yang 6,  Jiao Qian 7
Affiliations

Affiliations

  • 1 Department of Pharmacy, The First Affiliated Hospital (Changhai Hospital), Naval Medical University, Shanghai, China.
  • 2 Naval Medical University, Shanghai, China.
  • 3 Department of Diving and Hyperbaric Medicine, Naval Special Medicine Center, Naval Medical University, Shanghai, China.
  • 4 Department of Dermatology, The First Affiliated Hospital (Changhai Hospital), Naval Medical University, Shanghai, China.
  • 5 Department of Obstetrics and Gynecology, People's Hospital of Rugao City, Rugao, China.
  • 6 Department of Orthopedics, The Second Affiliated Hospital (Changzheng Hospital), Naval Medical University, Shanghai, China. yangjunspine@163.com.
  • 7 Department of Pharmacy, The First Affiliated Hospital (Changhai Hospital), Naval Medical University, Shanghai, China. qianjiaosmmu@163.com.
  • # Contributed equally.
PMID: 38884699 DOI: 10.1007/s12640-024-00708-0
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.

Keywords

Central nervous system oxygen toxicity; Mitochondria; Oxidative stress; PGC-1α; Polyethylene glycol 300.

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