首页|Hyperbaric oxygen therapy attenuates carbon monoxide-induced lung injury by restoring mitochondrial dynamics and suppressing Pink1/ Parkin-mediated mitophagy
Hyperbaric oxygen therapy attenuates carbon monoxide-induced lung injury by restoring mitochondrial dynamics and suppressing Pink1/ Parkin-mediated mitophagy
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NETL
NSTL
Elsevier
Carbon monoxide (CO), a major air pollutant from vehicle emissions, industrial combustion, and indoor fuel use, poses significant environmental and public health risks. Although acute carbon monoxide poisoning (COP) is well-documented, the underlying mechanisms driving long-term pulmonary complications following CO exposure remain poorly understood. Hyperbaric oxygen therapy (HBOT) is the standard treatment for COP, primarily for its ability to eliminate carboxyhemoglobin and reduce oxidative stress. However, its role in preventing longterm pulmonary dysfunction through the regulation of mitochondrial quality control requires further investigation. This study aimed to elucidate how mitochondrial dynamics and Pink1/Parkin-mediated mitophagy contribute to CO-induced lung injury and to evaluate the therapeutic potential of HBOT. Epidemiological analysis revealed an association between COP and an increased chronic obstructive pulmonary disease (COPD) risk. In a rat model, CO exposure led to emphysematous lung damage, persistent cytokine storms, and immune dysregulation. CD86+ and CD163+ macrophages and neutrophils were found in both bronchoalveolar lavage fluid and lung parenchyma, coexpressing pro-inflammatory cytokines (e.g., CCL5, CCL20, IL-1 beta, IL-10, IL-17). Alveolar barrier integrity was disrupted by downregulation of tight junction proteins ZO-1 and claudin 3. In alveolar type II cells, mitochondrial dynamics were impaired (decreased Opa1, increased Drp1), with concurrent activation of Pink1/Parkin-mediated mitophagy, pyroptosis, and apoptosis. These alterations led to alveolar damage and pulmonary dysfunction, including increased airway resistance, compliance, and hyperinflation-hallmarks of COPD-like pathology. Notably, HBOT reversed these changes by restoring mitochondrial homeostasis, suppressing cell death pathways, reducing inflammation, and improving lung function. These findings provide novel insights into the role of mitochondrial dynamics and selective mitophagy in the pathogenesis of CO-induced lung injury. It also underscores the therapeutic potential of HBOT in preventing and controlling long-term pulmonary complications.
NETL
NSTL
Elsevier
