PEG300 Protects Mitochondrial Function By Upregulating PGC-1α to Delay Central Nervous System Oxygen Toxicity in Mice.
Xin LiYue ShenDan LiKun ZhangJia LiuLu YaoJun YangJiao QianPublished in: Neurotoxicity research (2024)
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.
Keyphrases
- oxidative stress
- drug delivery
- skeletal muscle
- high fat diet induced
- blood brain barrier
- dna damage
- gene expression
- healthcare
- public health
- diabetic rats
- cerebral ischemia
- poor prognosis
- ischemia reperfusion injury
- insulin resistance
- type diabetes
- cerebrospinal fluid
- adipose tissue
- subarachnoid hemorrhage
- health information
- mental health
- current status
- brain injury
- wild type
- human health