Understanding the relationship between lung GABAA receptors and aquaporin-1: a new therapeutic approach for acute lung injury

Background: This study aimed to investigate the effects of the GABAA receptor and the potential relationship between GABA/ GABAA receptor signalling and aquaporin-1 in acute lung injury (ALI). Methods: Fifty-six male Wistar albino rats (220–240 g) were divided into seven groups. Two groups received intraperitoneal diazepam at 5 or 10 mg/kg. In two other groups, 0.1 mg/kg flumazenil was administered five minutes after diazepam. Thirty minutes after the final treatment, all groups except the healthy controls were subjected to an LPS- induced ALI model. Lung tissue were collected 24 h after LPS administration and analysed using histopathological, molecular, and biochemical methods. Results: In the present study, it was found that aquaporin-1, which plays an important regulatory role in LPS-damaged lung tissue, decreased and the weight of lung tissue increased in wet/dry analysis of a murine model of ALI. The levels of IL-1β, IL-6, and TNF-α were found to be elevated. Additionally, in groups treated with the GABAA receptor modulator diazepam, the levels of these inflammatory cytokines were significantly reduced and in parallel a significant increase in aquaporin-1 expression was observed. Conclusion: Diazepam, acting as a GABAA receptor modulator, may alleviate ALI by reducing inflammation and enhancing aquaporin-1 expression via GABAA receptor activation. © The Author(s) 2026.