Background: Neuronal ferroptosis is a major cause of cognitive impairment and mortality in patients with sepsis-associated encephalopathy (SAE). A low dose of acetaminophen (APAP) in septic mice can prevent ferroptosis in the hippocampal tissue; however, the underlying mechanism is unknown. This study aimed to investigate the mechanism by which APAP reduces ferroptosis in the hippocampal tissues of septic mice.
Methods: A mouse model of SAE was established, and the ferroptosis pathway inhibitors RSL3 and iFSP1+RSL3 were used in addition to APAP for the interventions, respectively. The 7-day survival rate of the mice was recorded, and cognitive function was examined using the Morris water maze test. Hematoxylin and eosin staining was performed to observe hippocampal tissue damage. Hippocampal iron and malondialdehyde (MDA) were measured using chemical colorimetric methods. Immunofluorescence was used to detect the reactive oxygen species (ROS) content in hippocampal tissues.
Results: RSL3 reversed the efficacy of APAP on improving cognitive dysfunction in septic mice but did not obviously reverse the survival rate of mice enhanced by APAP. RSL3 aggravated APAP-induced hippocampal tissue damage in mice attenuated by APAP. RSL3 inhibited glutathione peroxidase 4 (GPX4) expression and increased ferroptosis suppressor protein 1 (FSP1) and 4-hydroxy-2-nonenal (4-HNE) expression. RSL3 also reversed the effects of APAP in reducing iron, MDA, and ROS levels in the hippocampal tissues of septic mice. iFSP1+RSL3 further reversed the effect of APAP on ameliorating cognitive dysfunction in septic mice and successfully reversed the survival rate of mice enhanced by APAP. iFSP1+RSL3 aggravated APAP-induced cerebral hippocampal damage. iFSP1+RSL3 inhibited both GPX4 and FSP1, further reversing the effect of APAP on the reduction in iron, 4-HNE, ROS, and MDA levels in the cerebral hippocampus of mice with sepsis.
Conclusion: These data suggest that APAP inhibits ferroptosis in the cerebral hippocampus of septic mice through the GPX4 and FSP1 pathways.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10454284 | PMC |
| http://dx.doi.org/10.1002/brb3.3145 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Suppression of Sepsis Cytokine Storm by Escherichia Coli Cell Wall-Derived Carbon Dots.
Adv Mater
January 2025
State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, 300350, China.
Article Synopsis
- Sepsis is a severe condition caused by an uncontrolled immune reaction to infections, often involving harmful bacteria like E. coli, and currently lacks effective treatments.
- Researchers developed E. coli wall-derived carbon dots (E-CDs) that can reduce inflammation and improve survival rates in septic mice by binding to immune receptors and preventing excessive immune responses.
- E-CDs also show promise in other models, reducing inflammation and oxidative stress, suggesting they could be a new therapeutic approach for treating sepsis by utilizing pathogen-derived materials.
Immunotherapeutic potentials of carnosol against lipopolysaccharides-induced acute inflammatory reactions in White Swiss albino mice.
Immunopharmacol Immunotoxicol
February 2025
Nutrition Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Septic shock involves severe systemic inflammatory reaction toward various invading species, such as microorganisms and microbial toxins. Such a response is complicated and characterized as being a dynamic and time-dependent phenomenon. During this response, a significant amount of pro-inflammatory cytokines may be produced, causing a rapid death rate in septic victims and occasionally leading to apoptosis of immune cells within the first hours of septic reaction.
View Article and Find Full Text PDFFocal Septic Arthritis Elicits Age and TLR2-Dependent Periarticular Bone Loss.
J Inflamm Res
December 2024
Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Introduction: Septic arthritis, primarily caused by (), is a severe joint infection that leads to joint and bone damage. lipoproteins (LPPs) bind to Toll-like Receptor 2 (TLR2), inducing arthritis and localized bone loss. Aging affects TLR2 immune response to pathogens.
View Article and Find Full Text PDFFunctional connectivity within sensorimotor cortical and striatal regions is regulated by sepsis in a sex-dependent manner.
Neuroimage
January 2025
Department of Psychiatry, University of Florida, Gainesville, FL 32610, USA; McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA. Electronic address:
Article Synopsis
- Sepsis leads to systemic immune issues and organ failure, often resulting in severe brain disability, with young females showing better recovery than males.
- Using a mouse model, researchers found that after experiencing sepsis, both male and female mice showed weight regain and reduced gut microbiome diversity, but males displayed more significant immune changes and brain inflammation.
- fMRI analysis highlighted that while both sexes experienced similar changes in certain brain areas, male mice had altered connectivity patterns suggesting a delayed recovery process compared to females, indicating a complex, sex-dependent response to sepsis.
The tryptophan metabolite kynurenic acid ameliorates septic colonic injury through activation of the PPARγ signaling pathway.
Int Immunopharmacol
December 2024
Department of Trauma-Emergency & Critical Care Medicine, Shanghai Fifth People's Hospital, Fudan University, 128 Ruili Road, Shanghai 200240, China. Electronic address:
Sepsis is the leading cause of death among critically ill patients in clinical practice, making it urgent to reduce its incidence and mortality rates. In sepsis, macrophage dysfunction often worsens and complicates the condition. M1 and M2 macrophages, two distinct types, contribute to pro-inflammatory and anti-inflammatory effects, respectively.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!