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

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.

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Funding

We were supported by Bozok University, Department of Scientific Research Projects, (Project No: 6602b-TF/18-193).

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MÇ projected and conducted the study, analyzed the data, and wrote the study. MÇ and ST operated rats. ZD and EK performed histopathological and immunohistochemical analyzes. PÇ made ELISA analysis.

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Correspondence to Murat Çakır.

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Çakır, M., Tekin, S., Doğanyiğit, Z. et al. The protective effect of cannabinoid type 2 receptor activation on renal ischemia–reperfusion injury. Mol Cell Biochem 462, 123–132 (2019). https://doi.org/10.1007/s11010-019-03616-6

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  • DOI: https://doi.org/10.1007/s11010-019-03616-6

Keywords

  • Kidney
  • Cannabinoid type 2 receptor
  • Ischemia–reperfusion injury
  • JWH-133