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Updated: Jan 20, 2026

An Effective Mouse Model of Unilateral Renal Ischemia-Reperfusion Injury
Published on: July 15, 2021
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.
Abstract:
Kidney ischemia reperfusion (IR) injury is an important health problem resulting in acute renal failure. After IR, the inflammatory and apoptotic process is triggered. The relation of Cannabinoid type 2 (CB2) receptor with inflammatory and apoptotic process has been determined. The CB2 receptor has been shown to be localized in glomeruli and tubules in human and rat kidney. Activation of CB2 receptor with JWH-133 has been shown to reduce apoptosis and inflammation. In this study, it was investigated whether CB2 activation with selective CB2 receptor agonist JWH-133 was protective against renal IR injury. Male Sprague-Dawley rats were divided into 5 groups (n = 45). Bilateral ischemia was treated to the IR group rat's kidneys for 45 min and then reperfusion was performed for 24 h. Three different doses of JWH-133 (0.2, 1 and 5 mg/kg) were administered to the treatment groups at the onset of ischemia. The JWH-133 application at three different doses decreased the glomerular and tubular damage. Additionally, in the renal tissue, nuclear factor-κB, tumour necrosis factor alpha, interleukin-1beta, and caspase-3 levels decreased immunohistochemically. Similarly, JWH-133 application decreased the serum tumour necrosis factor alpha, blood urea nitrogen, creatinine, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, Cystatin C, interleukin-18, interleukin-1beta, interleukin-6, and interleukin-10 levels. We found that JWH-133 and CB2 receptor activation had a curative effect against kidney IR damage. JWH-133 may be a new therapeutic agent in preventing kidney IR damage.
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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