Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Navigation/Suche
- Forscher*innen
- Institutionen
- Projekte
- Publikationen
- Partner
- Geldgeber
- Ausstattung
- Knowhow
- Forschungsfelder
"Köpfe" der aktuellen Meldungen:
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Hasegawa, T; Malle, E; Farhood, A; Jaeschke, H.
Generation of hypochlorite-modified proteins by neutrophils during ischemia-reperfusion injury in rat liver: attenuation by ischemic preconditioning.
AMER J PHYSIOL-GASTROINTEST L. 2005; 289(4): G760-G767.
Doi: 10.1152/ajpgi.00141.2005
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
Google Scholar
- Co-Autor*innen der Med Uni Graz
- Malle Ernst
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- Although it is well documented that neutrophils are critical for the delayed phase of hepatic ischemia-reperfusion injury, there is no direct evidence for a specific neutrophil-derived oxidant stress in vivo. Therefore, we used a model of 60 min of partial hepatic ischemia and 0-24 h of reperfusion to investigate neutrophil accumulation and to analyze biomarkers for a general oxidant stress [glutathione disulfide (GSSG) and malondialdehyde (MDA)] and for a neutrophil-specific oxidant stress [hypochlorite (HOCl)-modified epitopes] in rats. Plasma alanine transaminase activities and histology showed progressively increasing liver injury during reperfusion, when hepatic GSSG and soluble MDA levels were elevated. At that time, few neutrophils were present in sinusoids. However, the number of hepatocytes positively stained for HOCl-modified epitopes increased from 6 to 24 h of reperfusion, which correlated with the bulk of hepatic neutrophil accumulation and extravasation into the parenchyma. Consistent with a higher oxidant stress at later times, hepatic GSSG and protein-bound MDA levels further increased. Treatment with the NADPH oxidase inhibitor diphenyleneiodonium chloride attenuated postischemic oxidant stress (GSSG, protein-bound MDA, and hepatocytes positively stained for HOCl-modified epitopes) and liver injury at 24 h of reperfusion. Ischemic preconditioning suppressed all oxidant stress biomarkers, liver injury, and extravasation of neutrophils. In conclusion, extravasated neutrophils generate HOCl, which diffuses into hepatocytes and causes oxidative modifications of intracellular proteins during the neutrophil-mediated reperfusion injury phase. Ischemic preconditioning is an effective intervention for reduction of the overall inflammatory response and, in particular, for limitation of the cytotoxic activity of neutrophils during the later reperfusion period.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Aspartate Aminotransferases - metabolism
- Epitopes - metabolism
- Glutathione - metabolism
- Hypochlorous Acid - chemistry
- Immunohistochemistry - chemistry
- Ischemic Preconditioning - chemistry
- Leukocyte Count - chemistry
- Liver - metabolism
- Male - metabolism
- Malondialdehyde - metabolism
- NADPH Oxidase - antagonists and inhibitors
- Necrosis - antagonists and inhibitors
- Neutrophils - drug effects
- Oxidants - chemistry
- Oxidative Stress - physiology
- Proteins - metabolism
- Rats - metabolism
- Rats, Sprague-Dawley - metabolism
- Reperfusion Injury - metabolism
- Find related publications in this database (Keywords)
- hepatic oxidant stress biomarkersreactive oxygen specieshypochlorous acidmyeloperoxidase-hydrogen peroxide-chloride systemmalondialdehydelipid peroxidation