Related Experiment Video
Updated: Aug 22, 2026
A Novel Inhalation Mask System to Deliver High Concentrations of Nitric Oxide Gas in Spontaneously Breathing Subjects
Published on: May 4, 2021
Septic diaphragmatic dysfunction is prevented by Mn(III)porphyrin therapy and inducible nitric oxide synthase
Nicolás Nin1, Adriana Cassina, José Boggia
1Department of Pathophysiology, Hospital de Clínicas, School of Medicine, Universidad de la República , Avenida Italia s/n, Piso 15, CP 11600 Montevideo, Uruguay.
Objective:
Decreased diaphragmatic contractility and organ failure observed during sepsis is mediated by an overproduction of nitric oxide ((.)NO)-derived species, mitochondria being a major target of oxidative and nitrative stress. We tested the potential protective effects of (a) a novel synthetic antioxidant, the manganese(III) 5,10,15,20-tetrakis(N-ethylpyridinium-2-yl) porphyrin (MnTE-2-PyP(5+)) and (b) the inducible (.)NO synthase inhibitor aminoguanidine (AG) on a rat model of sepsis.
Setting:
University research laboratories.
Subjects And Interventions:
Sepsis was induced by cecal ligation and perforation in rats.
Measurements And Results:
Systemic hemodynamics, pulmonary gas exchange, in vitro diaphragmatic function and mitochondrial respiration were evaluated. Moreover, plasma and mitochondrial oxidative and nitrative stress parameters were investigated. Sepsis determined diaphragmatic dysfunction and a significant decrease in mitochondrial coupling and respiration. Oxidative stress was evidenced by decreased plasma antioxidants and increased lipid oxidation. Tyrosine nitration was increased in the plasma and mitochondria of the septic animals. These alterations were ameliorated or prevented by either MnTE-2-PyP(5+) or AG.
Conclusions:
Our results demonstrate that overproduction of (.)NO and (.)NO-derived reactive species play a critical role in mitochondrial impairment and diaphragmatic function during sepsis. More importantly, AG but mainly the novel metalloporphyrin MnTE-2-PyP(5+) were able to ameliorate diaphragmatic and mitochondrial dysfunction and could contribute to preventing organ failure during severe sepsis.
Insights
A novel antioxidant, MnTE-2-PyP(5+), and aminoguanidine (AG) protected against sepsis-induced diaphragmatic and mitochondrial dysfunction by reducing nitric oxide overproduction and oxidative stress.
Area of Science:
- Biomedical Science
- Biochemistry
- Pathophysiology
Background:
- Sepsis leads to decreased diaphragmatic contractility and organ failure.
- This is mediated by nitric oxide (NO)-derived species, targeting mitochondria and causing oxidative stress.
Purpose of the Study:
- To evaluate the protective effects of a novel antioxidant, manganese(III) 5,10,15,20-tetrakis(N-ethylpyridinium-2-yl) porphyrin (MnTE-2-PyP(5+)), and an NO synthase inhibitor, aminoguanidine (AG).
- To assess their impact on a rat model of sepsis-induced diaphragmatic and mitochondrial dysfunction.
Main Methods:
- Sepsis induced via cecal ligation and perforation in rats.
- Evaluated systemic hemodynamics, gas exchange, diaphragmatic function, and mitochondrial respiration.
- Measured plasma and mitochondrial oxidative and nitrative stress markers.
Main Results:
- Sepsis caused diaphragmatic dysfunction, reduced mitochondrial respiration, and increased oxidative and nitrative stress.
- These sepsis-induced alterations were significantly ameliorated or prevented by MnTE-2-PyP(5+) or AG treatment.
Conclusions:
- Overproduction of NO and its derivatives critically impairs mitochondria and diaphragmatic function in sepsis.
- MnTE-2-PyP(5+) and AG show potential in ameliorating sepsis-induced dysfunction, possibly preventing organ failure.
Related Concept Videos
01:26Mitral Stenosis III: Medical Management
01:27Mitral Stenosis IV: Nursing Management
01:14Myocarditis III: Medical Management
01:28Mitral Regurgitation IV: Nursing Management
01:18Endocarditis III: Medical Management
01:23Gastritis III: Clinical Manifestations and Management
Clinical manifestations of acute gastritis
The patient with acute gastritis may have a rapid onset of symptoms, such as epigastric pain or discomfort, dyspepsia, anorexia, hiccups, or nausea and vomiting, which can last from a few hours to a few days. Erosive or hemorrhagic gastritis may cause bleeding, which may manifest as blood in vomit or as...