Effect of ticagrelor on acute kidney injury in septic rats and its underlying mechanism

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Standardized Colon Ascendens Stent Peritonitis in Rats - a Simple, Feasible Animal Model to Induce Septic Acute Kidney Injury
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Standardized Colon Ascendens Stent Peritonitis in Rats - a Simple, Feasible Animal Model to Induce Septic Acute Kidney Injury

Published on: February 15, 2022

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Cheng Yu1, Cui-Min Gao1, Na Xie1

  • 1Department of Anesthesiology, First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China.

Experimental and Therapeutic Medicine
|March 26, 2021
PubMed

Insights

Ticagrelor treatment effectively reduced kidney damage and inflammation in a rat model of sepsis-induced acute kidney injury (AKI). These protective effects are linked to the downregulation of the CD62P pathway, suggesting a novel therapeutic mechanism.

Area of Science:

  • Nephrology
  • Pharmacology
  • Immunology

Background:

  • Sepsis-induced acute kidney injury (AKI) is a critical complication with high mortality.
  • The CD62P pathway plays a significant role in inflammatory responses and tissue damage during sepsis.
  • Ticagrelor, an antiplatelet drug, has shown potential in various inflammatory conditions.

Purpose of the Study:

  • To investigate the therapeutic effects of ticagrelor on sepsis-induced AKI in a rat model.
  • To elucidate the underlying mechanisms, specifically the involvement of the CD62P pathway.

Main Methods:

  • A rat model of sepsis-induced AKI was established using cecal ligation and puncture (CLP).
  • Rats were treated with different doses of ticagrelor (clinical and loading doses) or distilled water.
  • Key markers including serum creatinine, CD62P, interleukin-1β, myeloperoxidase activity, and renal cell apoptosis were assessed.

Main Results:

  • CLP significantly increased serum creatinine, CD62P, IL-1β, myeloperoxidase activity, and renal cell apoptosis compared to normal and sham groups.
  • Ticagrelor treatment significantly reduced these elevated markers in a dose-dependent manner.
  • CD62P expression was found to be closely associated with the development of sepsis-induced AKI.

Conclusions:

  • Ticagrelor demonstrates significant renoprotective effects in a rat model of sepsis-induced AKI.
  • The mechanism of action involves the reduction of inflammation, neutrophil infiltration, and renal cell apoptosis.
  • Downregulation of the CD62P pathway is a key mechanism underlying ticagrelor's therapeutic benefits in sepsis-induced AKI.
Keywords:
CD62Pacute kidney injuryapoptosisinflammationsepsisticagrelor

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