Oxidative Stress in Sepsis: A Focus on Cardiac Pathology

Abstract

This study aims to analyze post-mortem human cardiac specimens, to verify and evaluate the existence or extent of oxidative stress in subjects whose cause of death has been traced to sepsis, through immunohistological oxidative/nitrosative stress markers. Indeed, in the present study, i-NOS, NOX2, and nitrotyrosine markers were higher expressed in the septic death group when compared to the control group, associated with also a significant increase in 8-OHdG, highlighting the pivotal role of oxidative stress in septic etiopathogenesis. In particular, 70% of cardiomyocyte nuclei from septic death specimens showed positivity for 8-OHdG. Furthermore, intense and massive NOX2-positive myocyte immunoreaction was noticed in the septic group, as nitrotyrosine immunostaining intense reaction was found in the cardiac cells. These results demonstrated a correlation between oxidative and nitrosative stress imbalance and the pathophysiology of cardiac dysfunction documented in cases of sepsis. Therefore, subsequent studies will focus on the expression of oxidative stress markers in other organs and tissues, as well as on the involvement of the intracellular pattern of apoptosis, to better clarify the complex pathogenesis of multi-organ failure, leading to support the rationale for including therapies targeting redox abnormalities in the management of septic patients.

Management and Experiences in Diagnosing and Treating Acute Heart Failure in Children with Solid Tumors

“…This is primarily attributed to the tumor itself [1][2][3] or treatments such as chemotherapy 4 and surgery, which can compromise cardiac reserve function. Factors such as the high risk of infection 5,6 , electrolyte disturbances, stressors, anemia 7,8 , and frequent transfusions of various blood products during the bone marrow suppression period can all contribute to increased cardiac loading and consequently trigger acute cardiac dysfunction. Therefore, in the diagnosis and treatment of pediatric solid tumor patients, particular attention should be paid to cardiac function during the bone marrow suppression period.…”

The role and therapeutic potential of SIRTs in sepsis

“…Additionally, ROS disrupt endothelial cell function, causing increased vascular permeability ( 102 ). This allows inflammatory cells and fluid to enter tissues, leading to edema and organ dysfunction ( 103 , 104 ). Oxidative stress also affects immune cell function and responsiveness, impairing their ability to clear pathogens.…”

The Role of Oxidative Stress and Inflammatory Parameters in Heart Failure

“…Epidemiological studies have identified correlations between cardiovascular disease and the levels of 3-nitrotyrosine (NT), a marker of nitrosative stress, and asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase [76,92,93]. NT is a marker of nitrosative stress resulting from the nitration process, affecting tyrosine residues in plasma proteins and atherosclerotic lesions.…”

“…ADMA serves as an endogenous inhibitor of NO synthase, leading to enzyme uncoupling and subsequent peroxynitrite production, thereby inducing nitrosative stress in vascular endothelial and smooth muscle cells [76,92]. Oxidative and nitrosative stress can trigger immune responses and inflammasome activation, exacerbating inflammation and contributing to cardiovascular disease progression [92,93]. Ferlazzo et al evaluated the inflammatory status by analyzing the transcription levels of inflammasome-associated genes in peripheral blood mononuclear cells (PBMCs) from recruited subjects.…”

“…Nitrosative stress, evidenced by increased levels of 3-NT, plays a pivotal role in HFpEF pathogenesis, affecting the Inositol-Requiring Enzyme 1α-X-Box Binding Protein 1 (IRE1α-XBP1) pathway [76]. Elevated circulating 3-NT levels are associated with increased fibrosis and structural remodeling of the myocardium, highlighting their potential role as a diagnostic marker and therapeutic target [76,92,93].…”