Antihypertensive Agent Alleviates Sodium Hypochlorite-Induced Lung Injury

Bronchial asthma associated with acute or chronic lung injury has emerged as a significant public health concern due to environmental chemical pollution, particularly following the widespread application of sodium hypochlorite (NaClO) disinfectant during the COVID-19 pandemic. Captopril, an antihypertensive agent, has been shown to alleviate symptoms; understanding the mechanism of captopril-mediated protection could facilitate the development of more effective therapeutic strategies. BEAS-2B is a line of immortalized human bronchial epithelial cells, widely used as an in vitro model to investigate pulmonary toxicology. This study investigated the mechanism by which captopril protects the lung and BEAS-2B cells against NaClO-induced lung injury.

Lung injury was induced in mice by NaClO nebulization and in BEAS-2B cells by NaClO treatment. The role of captopril was investigated via physiological monitoring, angiotensin-converting enzyme (ACE) knockdown, and multiomic biochemical analyses focusing on reactive oxygen species (ROS) generation, mitochondrial integrity, and apoptotic/autophagic signaling pathways.

Captopril significantly inhibited NaClO-induced apoptosis and suppressed intracellular ROS, reducing oxidative products such as malondialdehyde (MDA) and oxidized glutathione, while simultaneously upregulating the expression of antioxidant enzymes. Furthermore, captopril reduced pro-inflammatory cytokine levels in BEAS-2B cells. It also reduced excessive mitochondrial ROS production and mitigated the NaClO-induced elevation of mitochondrial membrane potential. Notably, the protective effects of captopril were maintained in ACE gene-knockdown BEAS-2B cells, suggesting a potential ACE-independent mechanism. Captopril markedly alleviated NaClO-induced pulmonary injury, specifically improving NaClO-triggered lung dysfunction in mice. Mechanistically, captopril inhibited NaClO-induced apoptosis by upregulating B cell lymphoma 2 (Bcl-2) and downregulating FAS, cleaved caspase 3, and Bcl-2-associated X protein levels. This was linked to captopril suppressing tissue ROS generation, decreasing MDA content, elevating reduced glutathione, and enhancing the expression of antioxidant enzymes. Captopril also alleviated pulmonary and systemic inflammation and regulated autophagy-related proteins, thereby alleviating NaClO-induced dysregulation of autophagy.

Together, these findings indicate that captopril holds promise as a potent antioxidant agent to alleviate NaClO-induced lung injury. Antioxid. Redox Signal. 00, 000-000.