The protective effect of cannabinoid type 2 receptor activation on renal ischemia-reperfusion injury

Murat Çakır1, Suat Tekin2, Züleyha Doğanyiğit3

  • 1Faculty of Medicine, Department of Physiology, University of Yozgat Bozok, Yozgat, 66200, Turkey. murat.cakir@bozok.edu.tr.

Insights

Activation of the Cannabinoid type 2 (CB2) receptor with JWH-133 demonstrated a protective effect against kidney ischemia reperfusion (IR) injury. This therapeutic approach reduced inflammation and apoptosis, suggesting potential for treating acute renal failure.

Area of Science:

  • Nephrology
  • Immunology
  • Pharmacology

Background:

  • Kidney ischemia reperfusion (IR) injury is a significant cause of acute renal failure, characterized by inflammatory and apoptotic processes.
  • The Cannabinoid type 2 (CB2) receptor is implicated in modulating inflammatory and apoptotic pathways and is present in renal glomeruli and tubules.

Purpose of the Study:

  • To investigate the protective effects of selective CB2 receptor activation using JWH-133 against renal IR injury in a rat model.
  • To evaluate the impact of JWH-133 on histological damage, inflammatory markers, and apoptotic indicators in the kidneys.

Main Methods:

  • Male Sprague-Dawley rats underwent 45 minutes of bilateral ischemia followed by 24 hours of reperfusion.
  • Three different doses of JWH-133 (0.2, 1, and 5 mg/kg) were administered at the onset of ischemia.
  • Histological examination and immunohistochemical analysis were performed on renal tissue, alongside serum biochemical marker analysis.

Main Results:

  • JWH-133 administration at all tested doses significantly reduced glomerular and tubular damage.
  • Immunohistochemical analysis revealed decreased levels of nuclear factor-κB, tumor necrosis factor-alpha, interleukin-1beta, and caspase-3 in renal tissue.
  • Serum levels of various biomarkers, including tumor necrosis factor-alpha, blood urea nitrogen, creatinine, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, Cystatin C, and interleukins, were reduced by JWH-133 treatment.

Conclusions:

  • CB2 receptor activation with JWH-133 exhibits a curative effect against kidney IR injury.
  • JWH-133 demonstrates potential as a novel therapeutic agent for preventing and treating kidney IR damage.

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