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Targeting Oxidative Stress in Septic Acute Kidney Injury: From Theory to Practice
- Source :
- Journal of Clinical Medicine, Vol 10, Iss 3798, p 3798 (2021), Journal of Clinical Medicine
- Publication Year :
- 2021
- Publisher :
- MDPI AG, 2021.
-
Abstract
- Sepsis is the leading cause of acute kidney injury (AKI) and leads to increased morbidity and mortality in intensive care units. Current treatments for septic AKI are largely supportive and are not targeted towards its pathophysiology. Sepsis is commonly characterized by systemic inflammation and increased production of reactive oxygen species (ROS), particularly superoxide. Concomitantly released nitric oxide (NO) then reacts with superoxide, leading to the formation of reactive nitrogen species (RNS), predominantly peroxynitrite. Sepsis-induced ROS and RNS can reduce the bioavailability of NO, mediating renal microcirculatory abnormalities, localized tissue hypoxia and mitochondrial dysfunction, thereby initiating a propagating cycle of cellular injury culminating in AKI. In this review, we discuss the various sources of ROS during sepsis and their pathophysiological interactions with the immune system, microcirculation and mitochondria that can lead to the development of AKI. We also discuss the therapeutic utility of N-acetylcysteine and potential reasons for its efficacy in animal models of sepsis, and its inefficacy in ameliorating oxidative stress-induced organ dysfunction in human sepsis. Finally, we review the pre-clinical studies examining the antioxidant and pleiotropic actions of vitamin C that may be of benefit for mitigating septic AKI, including future implications for clinical sepsis.
- Subjects :
- septic acute kidney injury
vitamin C
Review
Bioinformatics
medicine.disease_cause
Systemic inflammation
Sepsis
chemistry.chemical_compound
Intensive care
Medicine
oxidative stress
Reactive nitrogen species
chemistry.chemical_classification
Reactive oxygen species
business.industry
hypoxia
Organ dysfunction
Acute kidney injury
General Medicine
medicine.disease
N-acetylcysteine
chemistry
medicine.symptom
business
Oxidative stress
Subjects
Details
- Language :
- English
- ISSN :
- 20770383
- Volume :
- 10
- Issue :
- 3798
- Database :
- OpenAIRE
- Journal :
- Journal of Clinical Medicine
- Accession number :
- edsair.doi.dedup.....3b95af5268e167f470e4d445d2f26b29