Sex-specific differences in lung mitochondrial function and injury in rats exposed to hyperoxia

Area of Science:

• Pulmonary Medicine
• Mitochondrial Biology
• Toxicology

Background:

• Hyperoxia is a critical therapy for Acute Respiratory Distress Syndrome (ARDS) but can cause lung injury.
• Sex-based differences in disease susceptibility and response to injury are increasingly recognized.

Purpose of the Study:

• To investigate sex differences in hyperoxia-induced acute lung injury (HALI) in adult rats.
• To explore the role of lung mitochondrial bioenergetics and hydrogen peroxide (H₂O₂) production in these sex differences.

Main Methods:

• Adult male and female rats were exposed to normoxia or hyperoxia for up to 60 hours.
• Lung injury was assessed using multiple physiological and histological parameters.
• Mitochondrial function, including oxygen consumption rates (OCRs) and H₂O₂ production (mtH₂O₂), was measured.

Main Results:

• Males exhibited more severe HALI than females, with greater weight loss and lung injury markers.
• Hyperoxia impaired mitochondrial OCRs in both sexes but decreased complex I expression only in males.
• Mitochondrial H₂O₂ production increased in females but not males, with complex II identified as the primary source.

Conclusions:

• Adult females are relatively protected from HALI compared to males.
• Complex II is a key source of mitochondrial H₂O₂ during hyperoxia.
• Sex is a critical variable to consider in developing mitochondria-targeted therapies for HALI.