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Prior ischemic treatment renders kidney resistant to subsequent ischemia
1Department of Veterinary Physiology, College of Veterinary Medicine, Biotechnology Research Institute, Chonnam National University, Kwangju 500-757, Korea.
Abstract:
Prior ischemia leads to resistance against subsequent ischemic insults. The mechanisms that underlie this adaptive response remain unidentified. Thus, we studied whether the reduced susceptibility of mice previously subjected to the ischemia to ischemia/ reperfusion injury is related with altered inflammatory responses. Thirty minutes of bilateral kidney ischemia results in significantly increased plasma creatinine and blood urea nitrogen levels in BALB/c male mice. There is severe disruption of actin cytoskeleton of proximal tubular cells in the outer stripe of the outer medulla 24 hours post-ischemia. When mice are subjected to 30 minutes of bilateral ischemia 8 days later, there is no increase in plasma creatinine and blood urea nitrogen levels and the post-ischemic disruption of actin cytoskeleton of proximal tubular cells is much less. Inflammatory responses have highly implicated with ischemia/reperfusion injury. Ischemia results in the increased tissue myeloperoxidase (MPO) activity that is a marker of leukocyte infiltration. There is, however, no the post-ischemic increase of MPO activity in kidneys previously subjected to ischemia. Post-ischemic expression of tissue intercellular adhesion molecule-1 (ICAM-1) is greater in the kidney previously sham-operated than in the kidneys previously subjected to ischemia. In conclusion, prior ischemia protects kidney function and morphology against subsequent ischemia 8 days later. The resistance is associated with the reduced post-ischemic leukocyte infiltration due to the reduced post-ischemic ICAM-1 expression.
Insights
Prior ischemia protects kidneys from subsequent injury by reducing inflammatory responses. This adaptive mechanism involves decreased leukocyte infiltration and intercellular adhesion molecule-1 expression, preserving kidney function and structure.
Area of Science:
- Nephrology
- Immunology
- Physiology
Background:
- Prior ischemic events can induce resistance to subsequent ischemic insults.
- The underlying mechanisms of this adaptive response are not fully understood.
- Inflammation plays a significant role in ischemia/reperfusion injury.
Purpose of the Study:
- To investigate if prior ischemia alters inflammatory responses, conferring protection against subsequent ischemia/reperfusion injury.
- To determine the role of leukocyte infiltration and adhesion molecule expression in this protective effect.
Main Methods:
- Mice were subjected to bilateral kidney ischemia, followed by a second ischemic insult 8 days later.
- Kidney function was assessed by measuring plasma creatinine and blood urea nitrogen levels.
- Histological analysis examined actin cytoskeleton disruption in proximal tubular cells.
- Inflammatory markers, including myeloperoxidase (MPO) activity and intercellular adhesion molecule-1 (ICAM-1) expression, were measured.
Main Results:
- The second ischemic insult caused no significant increase in plasma creatinine or blood urea nitrogen levels in previously ischemic kidneys.
- Post-ischemic disruption of the actin cytoskeleton was significantly reduced in kidneys with prior ischemia.
- Kidneys with prior ischemia showed no increase in post-ischemic MPO activity.
- Reduced ICAM-1 expression was observed in kidneys subjected to prior ischemia compared to sham-operated controls.
Conclusions:
- Prior ischemia confers significant protection to kidney function and morphology against subsequent ischemia/reperfusion injury.
- This protective effect is associated with reduced post-ischemic leukocyte infiltration.
- The diminished inflammatory response, specifically lower ICAM-1 expression, underlies the observed resistance to injury.