Introduction <p>Ischemia/reperfusion injury (I/R) is common in various clinical situations. A growing body of clinical evidence suggests that renal I/R can trigger dysfunction in distant organs, underscoring the need for interventions that address both local and systemic effects. This study aimed to investigate the effect of allopurinol on distant organ damages induced by renal I/R.</p> Methods <p>Twelve Sprague-Dawley rats were randomly divided into groups: (I) Sham, (II) I/R, and (III) I/R + Allopurinol. Renal I/R was induced by bilateral clamping of the renal pedicles for 60&#xa0;min, followed by 24&#xa0;h of reperfusion. A single dose of allopurinol (100&#xa0;mg/kg, gavage) was administered 1&#xa0;h before I/R. At the end of 24&#xa0;h, electrocardiograms and mean blood pressure were recorded. Functional biomarkers, pathological findings, and oxidative stress levels were assessed in the tissue samples of the experimental groups.</p> Result <p>Renal I/R injury significantly increased the functional biomarkers of the kidneys (Cr and BUN), heart (LDH and cardiac troponin I), and liver enzymes (ALT, AST, and, APT). Pathological changes were significant in both the site of ischemia and the distant organs. Total oxidative status increased, while total antioxidant capacity decreased in the lung, liver, and heart tissues of the I/R group. Allopurinol pretreatment significantly restored the plasma levels of functional biomarkers and oxidative stress in the lung, heart, and liver tissues. Allopurinol pretreatment improved the pathological damage in the kidneys and distant organs.</p> Conclusion <p>Allopurinol, a xanthine oxidase inhibitor, was able to reverse the structural damage and functional disorders of the kidney and remote organs caused by renal ischemia by modulating the oxidative stress pathway.</p> Clinical trial number <p>Not applicable.</p>

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Allopurinol mitigates distant organ damage following bilateral renal ischemia-reperfusion injury in male rats

  • Pooran Ghahramani,
  • Vahideh Yavari,
  • Zeinab Karimi

摘要

Introduction

Ischemia/reperfusion injury (I/R) is common in various clinical situations. A growing body of clinical evidence suggests that renal I/R can trigger dysfunction in distant organs, underscoring the need for interventions that address both local and systemic effects. This study aimed to investigate the effect of allopurinol on distant organ damages induced by renal I/R.

Methods

Twelve Sprague-Dawley rats were randomly divided into groups: (I) Sham, (II) I/R, and (III) I/R + Allopurinol. Renal I/R was induced by bilateral clamping of the renal pedicles for 60 min, followed by 24 h of reperfusion. A single dose of allopurinol (100 mg/kg, gavage) was administered 1 h before I/R. At the end of 24 h, electrocardiograms and mean blood pressure were recorded. Functional biomarkers, pathological findings, and oxidative stress levels were assessed in the tissue samples of the experimental groups.

Result

Renal I/R injury significantly increased the functional biomarkers of the kidneys (Cr and BUN), heart (LDH and cardiac troponin I), and liver enzymes (ALT, AST, and, APT). Pathological changes were significant in both the site of ischemia and the distant organs. Total oxidative status increased, while total antioxidant capacity decreased in the lung, liver, and heart tissues of the I/R group. Allopurinol pretreatment significantly restored the plasma levels of functional biomarkers and oxidative stress in the lung, heart, and liver tissues. Allopurinol pretreatment improved the pathological damage in the kidneys and distant organs.

Conclusion

Allopurinol, a xanthine oxidase inhibitor, was able to reverse the structural damage and functional disorders of the kidney and remote organs caused by renal ischemia by modulating the oxidative stress pathway.

Clinical trial number

Not applicable.