Evaluation of the role of the cannabidiol system in an animal model of ischemia/reperfusion kidney injury

Kidney injury was induced by 45 minutes of renal ischemia followed by reperfusion. Cannabidiol (5mg/kg) was administered immediately after reperfusion.

Results:

Ischemia/reperfusion increased the IL-1 and TNF levels, and these levels were attenuated by cannabidiol treatment. Additionally, cannabidiol was able to decrease lipid and protein oxidative damage, but not the nitrite/nitrate levels. Kidney injury after ischemia/reperfusion seemed to be independent of the cannabidiol receptor 1 and cannabidiol receptor 2 (CB1 and CB2) expression levels, as there was no significant increase in these receptors after reperfusion.

Conclusion:

The cannabidiol treatment had a protective effect against inflammation and oxidative damage in the kidney ischemia/reperfusion model. These effects seemed to be independent of CB1/CB2 receptor activation.

Keywords:
Cannabidiol/therapeutic use; Receptors, cannabinoid; Ischemia/metabolism; Reperfusion injury/metabolism; Kidney/injuries; Inflammation

Authorship

Rodrigo Zon Soares

Laboratory of Experimental Physiopathology, Graduate Program in Health Sciences, Health Sciences Unit, Universidade do Extremo Sul Catarinense - Criciúma (SC), Brazil.Universidade do Extremo Sul CatarinenseBrazilCriciúma, SC, BrazilLaboratory of Experimental Physiopathology, Graduate Program in Health Sciences, Health Sciences Unit, Universidade do Extremo Sul Catarinense - Criciúma (SC), Brazil.

Francieli Vuolo

Dhébora Mozena Dall'Igna

Monique Michels

José Alexandre de Souza Crippa

Department of Neuroscience and Behavior, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo - São Paulo (SP), Brazil.Universidade de São PauloBrazilSão Paulo, SP, BrazilDepartment of Neuroscience and Behavior, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo - São Paulo (SP), Brazil.

Jaime Eduardo Cecílio Hallak

Antonio Waldo Zuardi

Felipe Dal-Pizzol Corresponding author: Felipe Dal-Pizzol, Laboratory of Experimental Physiopathology, Universidade do Extremo Sul Catarinense, Zip code: 88806-000 - Criciúma (SC), Brazil, E-mail: piz@unesc.net

Corresponding author: Felipe Dal-Pizzol, Laboratory of Experimental Physiopathology, Universidade do Extremo Sul Catarinense, Zip code: 88806-000 - Criciúma (SC), Brazil, E-mail: piz@unesc.net

Conflicts of interest: None.

SCIMAGO INSTITUTIONS RANKINGS

Figures

Figures (5)

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Figure 1
The effect of cannabidiol treatment on myeloperoxidase activity after renal ischemia reperfusion injury. Animals were sham operated or had their renal pedicle clamped bilaterally for 45 minutes. Immediately before unclamping, a single dose of cannabidiol (5mg/kg) or saline was administered. Twenty-four hours later, the myeloperoxidase activity was measured in the kidneys.

MPO - myeloperoxidase; CBD - cannabidiol. Data are expressed as mU/mg protein. ^# Different from ischemia/saline. p < 0.05.

Thumbnail

Figure 2
The effect of cannabidiol treatment on cytokine levels after renal ischemia reperfusion injury. Animals were sham operated or had their renal pedicle clamped bilaterally for 45 minutes. Immediately before unclamping, a single dose of cannabidiol (5mg/kg) or saline was administered. Twenty-four hours later, the IL-1 (A) and TNF-α (B) levels were measured in the kidneys.

CBD - cannabidiol. Data are expressed as pg/mg protein. * Different from control; ^# different from ischemia/saline. p < 0.05.

Thumbnail

Figure 3
The effect of cannabidiol treatment on oxidative damage parameter levels after renal ischemia reperfusion injury. Animals were sham operated or had their renal pedicle clamped bilaterally for 45 minutes. Immediately before unclamping, a single dose of cannabidiol (5mg/kg) or saline was administered. Twenty-four hours later, the thiobarbituric acid reactive species (A) and protein carbonyls (B) levels were measured in the kidneys.

MDA - malondialdehyde; CBD - cannabidiol. Data are expressed as nmol/mg protein. * Different from control; ^# different from ischemia/saline. p < 0.05.

Thumbnail

Figure 4
The effect of cannabidiol treatment on nitrite/nitrate levels after renal ischemia reperfusion injury. Animals were sham operated or had their renal pedicle clamped bilaterally for 45 minutes. Immediately before unclamping, a single dose of cannabidiol (5mg/kg) or saline was administered. Twenty-four hours later, the nitrite/nitrate levels were measured in the kidneys.

CBD - cannabidiol. Data are expressed as pg/mg protein. * Different from control. p < 0.05.

Thumbnail

Figure 5
The effect of cannabidiol treatment on the CB1 and CB2 levels after renal ischemia reperfusion injury. Animals were sham operated or had their renal pedicle clamped bilaterally for 45 minutes. Immediately before unclamping, a single dose of cannabidiol (5mg/kg) or saline was administered. Twenty-four hours later, the CB1 (A) and CB2 (B) levels were measured in the kidneys.

CBD - cannabidiol. The results were expressed as the relative ratio between the blot and the β-actin immunocontent. Order of bands: two bands Control; three bands Ischemia + saline; three bands Ischemia + CBD.

Figure 1 The effect of cannabidiol treatment on myeloperoxidase activity after renal ischemia reperfusion injury. Animals were sham operated or had their renal pedicle clamped bilaterally for 45 minutes. Immediately before unclamping, a single dose of cannabidiol (5mg/kg) or saline was administered. Twenty-four hours later, the myeloperoxidase activity was measured in the kidneys.
MPO - myeloperoxidase; CBD - cannabidiol. Data are expressed as mU/mg protein. ^# Different from ischemia/saline. p < 0.05.

Figure 2 The effect of cannabidiol treatment on cytokine levels after renal ischemia reperfusion injury. Animals were sham operated or had their renal pedicle clamped bilaterally for 45 minutes. Immediately before unclamping, a single dose of cannabidiol (5mg/kg) or saline was administered. Twenty-four hours later, the IL-1 (A) and TNF-α (B) levels were measured in the kidneys.
CBD - cannabidiol. Data are expressed as pg/mg protein. * Different from control; ^# different from ischemia/saline. p < 0.05.

Figure 3 The effect of cannabidiol treatment on oxidative damage parameter levels after renal ischemia reperfusion injury. Animals were sham operated or had their renal pedicle clamped bilaterally for 45 minutes. Immediately before unclamping, a single dose of cannabidiol (5mg/kg) or saline was administered. Twenty-four hours later, the thiobarbituric acid reactive species (A) and protein carbonyls (B) levels were measured in the kidneys.
MDA - malondialdehyde; CBD - cannabidiol. Data are expressed as nmol/mg protein. * Different from control; ^# different from ischemia/saline. p < 0.05.

Figure 4 The effect of cannabidiol treatment on nitrite/nitrate levels after renal ischemia reperfusion injury. Animals were sham operated or had their renal pedicle clamped bilaterally for 45 minutes. Immediately before unclamping, a single dose of cannabidiol (5mg/kg) or saline was administered. Twenty-four hours later, the nitrite/nitrate levels were measured in the kidneys.
CBD - cannabidiol. Data are expressed as pg/mg protein. * Different from control. p < 0.05.

Figure 5 The effect of cannabidiol treatment on the CB1 and CB2 levels after renal ischemia reperfusion injury. Animals were sham operated or had their renal pedicle clamped bilaterally for 45 minutes. Immediately before unclamping, a single dose of cannabidiol (5mg/kg) or saline was administered. Twenty-four hours later, the CB1 (A) and CB2 (B) levels were measured in the kidneys.
CBD - cannabidiol. The results were expressed as the relative ratio between the blot and the β-actin immunocontent. Order of bands: two bands Control; three bands Ischemia + saline; three bands Ischemia + CBD.

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Evaluation of the role of the cannabidiol system in an animal model of ischemia/reperfusion kidney injury

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[1] Corresponding author: Felipe Dal-Pizzol, Laboratory of Experimental Physiopathology, Universidade do Extremo Sul Catarinense, Zip code: 88806-000 - Criciúma (SC), Brazil, E-mail: piz@unesc.net