Antihypertensive agent Captopril alleviates NaClO-induced lung epithelial injury

Bronchial asthma with acute or chronic lung injury is emerging as a critical public health concern following the wave of extensive application of the disinfectant sodium hypochlorite (NaClO) during the COVID-19 pandemic. Captopril, an antihypertensive agent, is shown to relieve symptoms; elucidation of the mechanism of captopril-mediated protection will pave the way for inventing more effective therapeutic approaches. This study investigated the mechanism of the Captopril protection in NaClO-induced lung injury.Captopril significantly inhibited NaClO-induced apoptosis and suppressed intracellular reactive oxygen species (ROS). These resulted in the reduction of oxidative products malondialdehyde (MDA) and oxidized glutathione (GSSG), while upregulating the expression of antioxidant enzymes. Captopril also attenuated the levels of pro-inflammatory cytokines in BEAS-2B cells. Furthermore, captopril decreased the overproduction of mitochondrial ROS and alleviated the NaClO-induced elevation of mitochondrial membrane potential. Notably, the protective effects of captopril persisted in angiotensin-converting enzyme (ACE) gene-knockdown BEAS-2B cells, indicating an ACE-independent mechanism. Captopril markedly alleviated NaClO-induced pulmonary injury. Specifically, captopril effectively reduced NaClO-triggered lung dysfunction in mice. Captopril significantly reduced ACE activity, while compensatory ACE synthesis was observed. Captopril inhibited NaClO-induced apoptosis by upregulating Bcl-2 and downregulating FAS, cleaved caspase 3, and Bax levels. Moreover, captopril suppressed tissue ROS generation, decreased MDA content, elevated reduced glutathione (GSH), and enhanced antioxidant enzyme expression. Captopril relieved pulmonary and systemic inflammation and regulated autophagy-related proteins to alleviate NaClO-induced autophagy dysregulation. Together, this study reveals that captopril is a powerful agent with antioxidant potential to relieve NaClO-induced lung injury.