The preventive effect of cannabinoids on reperfusion-induced ischemia of mouse kidney

Feizi, Abdolamir; Jafari, Mohammad-Reza; Hamedivafa, Farzaneh; Tabrizian, Pouria; Djahanguiri, B

doi:10.1016/j.etp.2008.04.006

Cited by 32 publications

(22 citation statements)

References 27 publications

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“…In this study, the specific receptor activation was not evaluated, but the protection of the kidney was associated with reduced expression of proinflammatory factors (Fouad et al, 2012). In another study using a rodent model of renal IRI, tubular epithelial cell damage was prevented after dosedependent administration of either CB1 or CB2 receptor agonists (Feizi et al, 2008).…”

Section: Discussionmentioning

confidence: 90%

Selective Cannabinoid 2 Receptor Stimulation Reduces Tubular Epithelial Cell Damage after Renal Ischemia-Reperfusion Injury

Pressly

Mustafa

Adibi

et al. 2017

J Pharmacol Exp Ther

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Ischemia-reperfusion injury (IRI) is a common cause of acute kidney injury (AKI), which is an increasing problem in the clinic and has been associated with elevated rates of mortality. Therapies to treat AKI are currently not available, so identification of new targets that can be modulated to ameliorate renal damage upon diagnosis of AKI is essential. In this study, a novel cannabinoid receptor 2 (CB2) agonist, SMM-295 [3'-methyl-4-(2-(thiophen-2-yl)propan-2-yl)biphenyl-2,6-diol], was designed, synthesized, and tested in vitro and in silico. Molecular docking of SMM-295 into a CB2 active-state homology model showed that SMM-295 interacts well with key amino acids to stabilize the active state. In human embryonic kidney 293 cells, SMM-295 was capable of reducing cAMP production with 66-fold selectivity for CB2 versus cannabinoid receptor 1 and dose-dependently increased mitogen-activated protein kinase and Akt phosphorylation. In vivo testing of the CB2 agonist was performed using a mouse model of bilateral IRI, which is a common model to mimic human AKI, where SMM-295 was immediately administered upon reperfusion of the kidneys after the ischemia episode. Histologic damage assessment 48 hours after reperfusion demonstrated reduced tubular damage in the presence of SMM-295. This was consistent with reduced plasma markers of renal dysfunction (i.e., creatinine and neutrophil gelatinase-associated lipocalin) in SMM-295-treated mice. Mechanistically, kidneys treated with SMM-295 were shown to have elevated activation of Akt with reduced terminal deoxynucleotidyl transferase-mediated digoxigenin-deoxyuridine nick-end labeling (TUNEL)-positive cells compared with vehicle-treated kidneys after IRI. These data suggest that selective CB2 receptor activation could be a potential therapeutic target in the treatment of AKI.

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Section: Discussionmentioning

confidence: 90%

Selective Cannabinoid 2 Receptor Stimulation Reduces Tubular Epithelial Cell Damage after Renal Ischemia-Reperfusion Injury

Pressly

Mustafa

Adibi

et al. 2017

J Pharmacol Exp Ther

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“…First, while the role of the EC system in AKI has been examined through modulation of CB receptors in animal models of nephrotoxic tubular injury, this is the first investigation examining EC levels and the role of the EC system in ischemic AKI and renal IRI. 18 , 19 , 24 Therefore, the current findings shed light on how the EC system as a whole may be involved in the changes observed in renal IRI. Furthermore, our study demonstrates that renal IRI is associated with increased kidney 2-AG content.…”

Section: Discussionmentioning

confidence: 70%

“… 20–23 Despite the preponderance of evidence implicating the EC system and ECs in nonrenal IRI, data on the role of ECs in renal IRI remain sparse. 24 , 25 In addition, most of the studies examining the role of the EC system in renal injury focus on the effects of the activation or inhibition of the CB receptors and do not provide data on the tissue level of the endogenous ligands for these receptors, 2-AG and AEA. In this study, we show for the first time that renal IRI leads to a significant increase in renal level of 2-AG, one of the major activators of the EC system.…”

Section: Introductionmentioning

confidence: 99%

Increased Renal 2-Arachidonoylglycerol Level Is Associated with Improved Renal Function in a Mouse Model of Acute Kidney Injury

Moradi

Oveisi

Khanifar

et al. 2016

Cannabis and Cannabinoid Research

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Background: Acute kidney injury (AKI) is associated with a significantly increased risk of morbidity and mortality. Ischemia–reperfusion injury (IRI) is a major cause of AKI. In this study, we investigated the role of the endocannabinoid (EC) system in renal IRI using a well-established mouse model.Materials and Methods: Renal ischemia was induced in male C57BL/6 mice by clamping both kidney pedicles for 30 min followed by 24 h of reperfusion. To increase renal 2-arachidonoylglycerol (2-AG) levels, mice were pretreated with JZL184 (16 mg/kg), 30 min before IRI. Serum creatinine and blood urea nitrogen (BUN), renal tubular damage, renal content of ECs and renal expression of markers of inflammation and oxidative stress were measured.Results: Renal IRI was associated with significantly increased serum BUN and creatinine, increased tubular damage score, increased expression of renal markers of inflammation and oxidative stress and elevated renal 2-AG content. Pretreatment with JZL184 was associated with a significant increase in renal 2-AG content and there was also improved serum BUN, creatinine and tubular damage score. However, renal expression of inflammation and oxidative stress markers remained unchanged.Conclusions: This is the first report documenting that renal IRI is associated with an increase in kidney 2-AG content. Further enhancement of 2-AG levels using JZL184 improved indices of renal function and histology, but did not lower renal expression of markers of inflammation and oxidative stress. Further studies are needed to determine the mechanisms responsible for the effects observed and the potential value of 2-AG as a therapeutic target in renal IRI.

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“…Feizi et al . () showed that endocannabinoid analogues could prevent the appearance of characteristic lesions present in kidneys due to ischaemia and reperfusion injury. In addition, Mukhopadhyay et al .…”

Section: Discussionmentioning

confidence: 99%

The endocannabinoid system in renal cells: regulation of Na⁺ transport by CB₁ receptors through distinct cell signalling pathways

Sampaio

Silva

Lima

et al. 2015

British J Pharmacology

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Background and Purpose The function of the endocannabinoid system (ECS) in renal tissue is not completely understood. Kidney function is closely related to ion reabsorption in the proximal tubule, the nephron segment responsible for the re‐absorption of 70–80% of the filtrate. We studied the effect of compounds modulating the activity of cannabinoid (CB) receptors on the active re‐absorption of Na+ in LLC‐PK1 cells. Experimental Approach Changes in Na+/K+‐ATPase activity were assessed after treatment with WIN55,212‐2 (WIN), a non‐selective lipid agonist, and haemopressin (HP), an inverse peptide agonist at CB1 receptors. Pharmacological tools were used to investigate the signalling pathways involved in the modulation of Na+ transport. Key Results In addition to CB1 and CB2 receptors and TRPV1 channels, the mRNAs encoding for enzymes of the ECS were also expressed in LLC‐PK1. WIN (10−7 M) and HP (10−6 M) altered Na+ re‐absorption in LLC‐PK1 in a dual manner. They both acutely (after 1 min) increased Na+/K+‐ATPase activity in a TRPV1 antagonist‐sensitive way. WIN's stimulating effect persisted for 30 min, and this effect was partially blocked by a CB1 antagonist or a PKC inhibitor. In contrast, HP inhibited Na+/K+‐ATPase after 30 min incubation, and this effect was attenuated by a CB1 antagonist or a PKA inhibitor. Conclusion and Implications The ECS is expressed in LLC‐PK1 cells. Both CB1 receptors and TRPV1 channels regulate Na+/K+‐ATPase activity in these cells, and are modulated by lipid and peptide CB1 receptor ligands, which act via different signalling pathways.

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The preventive effect of cannabinoids on reperfusion-induced ischemia of mouse kidney

Cited by 32 publications

References 27 publications

Selective Cannabinoid 2 Receptor Stimulation Reduces Tubular Epithelial Cell Damage after Renal Ischemia-Reperfusion Injury

Selective Cannabinoid 2 Receptor Stimulation Reduces Tubular Epithelial Cell Damage after Renal Ischemia-Reperfusion Injury

Increased Renal 2-Arachidonoylglycerol Level Is Associated with Improved Renal Function in a Mouse Model of Acute Kidney Injury

The endocannabinoid system in renal cells: regulation of Na⁺ transport by CB₁ receptors through distinct cell signalling pathways

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The preventive effect of cannabinoids on reperfusion-induced ischemia of mouse kidney

Cited by 32 publications

References 27 publications

Selective Cannabinoid 2 Receptor Stimulation Reduces Tubular Epithelial Cell Damage after Renal Ischemia-Reperfusion Injury

Selective Cannabinoid 2 Receptor Stimulation Reduces Tubular Epithelial Cell Damage after Renal Ischemia-Reperfusion Injury

Increased Renal 2-Arachidonoylglycerol Level Is Associated with Improved Renal Function in a Mouse Model of Acute Kidney Injury

The endocannabinoid system in renal cells: regulation of Na+ transport by CB1 receptors through distinct cell signalling pathways

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The endocannabinoid system in renal cells: regulation of Na⁺ transport by CB₁ receptors through distinct cell signalling pathways