Reactive Oxygen Species and Strategies for Antioxidant Intervention in Acute Respiratory Distress Syndrome

Abstract

Acute respiratory distress syndrome (ARDS) is a life-threatening pulmonary condition characterized by the sudden onset of respiratory failure, pulmonary edema, dysfunction of endothelial and epithelial barriers, and the activation of inflammatory cascades. Despite the increasing number of deaths attributed to ARDS, a comprehensive therapeutic approach for managing patients with ARDS remains elusive. To elucidate the pathological mechanisms underlying ARDS, numerous studies have employed various preclinical models, often utilizing lipopolysaccharide as the ARDS inducer. Accumulating evidence emphasizes the pivotal role of reactive oxygen species (ROS) in the pathophysiology of ARDS. Both preclinical and clinical investigations have asserted the potential of antioxidants in ameliorating ARDS. This review focuses on various sources of ROS, including NADPH oxidase, uncoupled endothelial nitric oxide synthase, cytochrome P450, and xanthine oxidase, and provides a comprehensive overview of their roles in ARDS. Additionally, we discuss the potential of using antioxidants as a strategy for treating ARDS.

Keywords: acute lung injury; acute respiratory distress syndrome; antioxidant; glutathione; reactive oxygen species; superoxide dismutase; vitamins.

Figure 1

Overview of the roles of reactive oxygen species (ROS) in the pathophysiology of ARDS. ROS originating from various intrinsic and extrinsic sources leads to oxidative stress, cell-mediated inflammation, and damage to epithelial and endothelial cells. These processes are driven by the activation of multiple signaling pathways, ultimately contributing to the onset and progression of ARDS.

Figure 2

ROS-mediated signaling pathways. The signaling pathways involving ROS include the activation of NFκB and MAPK pathways. Specifically, ROS can activate NFκB through the phosphorylation of IκB and induce the phosphorylation of the MAPK pathway, which includes JNK, ERK, and p38 MAPK. Consequently, these activations promote the nuclear translocation of transcriptional factors such as NFκB, AP-1, c-Fos, c-Jun, and NRF2. These factors contribute to the regulation of genes associated with oxidant defenses.