Role of oxidative stress in sepsis: Mechanisms, pathways, and therapeutic strategies

Sepsis, a life-threatening condition caused by dysregulated host response to infection, leads to high morbidity and mortality, primarily due to sepsis-induced organ dysfunction. Oxidative stress, driven by excessive reactive oxygen species (ROS), plays a central role in sepsis pathophysiology, exacerbating inflammation, mitochondrial dysfunction, and cellular damage in multiple organs, including the heart, kidneys, liver, lungs, brain, and skeletal muscles. This review provides a comprehensive analysis of mechanisms by which oxidative stress contributes to sepsis-induced organ injury. Most current research examining the interplay between ROS, inflammation, mitochondrial dysfunction, and cell death pathways such as apoptosis, ferroptosis, and pyroptosis, are animal- or cell-based. Key signaling pathways, including nuclear factor κB (NF-κB), NLR family pyrin domain-containing 3 inflammasome (NLRP3), nuclear factor erythroid 2-related factor 2 (Nrf-2)/heme oxygenase-1 (HO-1), and phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt), are explored as potential therapeutic targets. This review also highlights the roles of mitochondrial quality control (MQC), autophagy, and noncoding RNAs in mitigating oxidative damage.