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

doi:10.1016/j.etp.2008.04.006

Experimental and Toxicologic Pathology

Volume 60, Issues 4–5, 5 August 2008, Pages 405-410

https://doi.org/10.1016/j.etp.2008.04.006 Get rights and content

Abstract

Artery occlusion of an organ results in ischemia. When the occlusion is opened and blood flow reinstated there will be tissue injuries identified as reperfusion-induced ischemia (RII). It has been suggested that cannabinoids (CBs) may be involved in the RII. In this study, we assessed the effect of different doses of anandamide analogs and CB receptor agonists: arachidonylcyclopropylamide (ACPA, a CB1 agonist) and JWH133 (a CB2 agonist) in the RII of the mouse kidney. Three doses (0.2, 1 and 5 mg/kg, i.p.) of ACPA or JWH133 were used 30 min prior initiation of RII. Kidneys were removed 2 and 24 h following RII and checked histologically for the grading of ischemic injury. Appropriate control groups were used as well. RII produced lesion comparable with that of ischemia. Different doses of ACPA or JWH133 prevented RII-induced lesions. It is suggestive of the CB system involvement in the kidney RII in mice.

Introduction

Prior exposure to brief periods of tissue ischemia leads to a state of increased tolerance to the effects of subsequent reperfusion-induced ischemia (RII). This phenomenon was referred to as ischemic preconditioning (IP). Murry et al. (1986) documented and defined the protective effect of “IP” in cardiac muscle. The concept of IP has been extended to several organs including the brain (Heurteaux et al., 1995), liver (Peralta et al., 1999) and skeletal muscle (Schroeder et al., 1996). However, evidence supporting a role for IP in protecting against ischemic–reperfusion injury in kidney was scant and controversial (Islam et al., 1997, Turman and Bates, 1997) until Lee and Emala (2000) in an in-vivo experiment demonstrated the protective effect of IP in the kidney of rats. The precise mechanisms, by which IP reduces the RII, remain obscure. Several factors have been reported to contribute to IP-mediated tissue protection. In cardiac IP, the translocation and activation of myocardial protein kinase C (PKC), which is caused by increased production of adenosine and A1 receptor activation, plays an important role in myocardial protection (Downey et al., 1993). Activated PKC is also known to lead to the activation of ATP-sensitive potassium (K_ATP) channels, which appears to be closely related to IP-induced tissue protection (Auchampach and Gross, 1993). Recent studies indicated the important role of mitochondrial K_ATP channels in the cardioprotective effect of IP (Gross and Fryer, 1999, Miura et al., 2000). There is accumulating evidence that nitric oxide (NO) production (Bolli et al., 1997; Takano et al., 1998), antioxidant enzyme activation (Currie et al., 1988) and cardiac heat stress protein synthesis (Hutter et al., 1994; Marber et al., 1994) are also involved in IP-mediated cardioprotection.

Several reports have confirmed the beneficial effects of cannabinoids (CBs) on IP in the rat coronary artery occlusion-induced ischemia (Bouchard et al., 2003; Joyeux et al., 2002; Ribuot et al., 2005) which is suggested to be partly through NO contribution (Joyeux et al., 2002; Ribuot et al., 2005).

Therefore, the aim of the present study was to examine the possible preventive action of CB (CB1 and CB2) receptor agonists on RII of mouse kidney.

Section snippets

Animals

We used female albino NMRI mice weighing 20.3–29.7 g. The animals were housed in groups of eight in Plexiglas cages with a 12 h light/12 h dark cycle and controlled temperature (22±2 °C). They were given food and water ad libitum. Each animal was used only once per experiment and all procedures were carried out in accordance with institutional guidelines for animal care and use.

Surgical procedures

Mice were anesthetized with ketamine+zylasine (100/20 mg/kg, i.p., Alfasan, Holland). The abdomen was opened and after

Effect of cannabinoid receptor agonist on RII after 2 h reperfusion

The results are summarized in Table 1. Intraperitoneal injection of emulsion vehicle, ACPA or JWH133 followed by anesthesia in control groups produced no kidney lesion (H (3)=0, P=1) (Fig. 1). Occlusion of the left kidney artery for 30 min followed by 2 h of reperfusion (group II) produced moderate kidney lesion in animals (Fig. 2, Fig. 3, Fig. 4). The scores of the lesion in this group were the highest seen (four mice with grade 4 and two mice with grades 3 and 2). ACPA at the dose of 0.2, 1 and

Discussion

In the present study, we have demonstrated that CB agonists prevent reperfusion-induced ischemia in the mouse kidney.

RII is regarded as one of the important complications of organ transplantation. Animal studies demonstrated that reperfusion of ischemic area, in particular readmission of oxygen, contributes to future tissue damage. Although investigations to study the effects of varying durations of renal ischemia date back to the early 1960s, they failed to generate research interests until

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

Abstract

Introduction

Section snippets

Animals

Surgical procedures

Effect of cannabinoid receptor agonist on RII after 2 h reperfusion

Discussion

FEBS Lett

Life Sci

Bioorg Med Chem

J Pharmacol Sci

Int J Cardiol

J Am Coll Cardiol

Ann Cardiol Angeiol (Paris)

J Am Coll Cardiol

Nitric oxide-angiotensin II axis in renal and cardiovascular injury

J Nephrol

Adenosine A1 receptor, KATP channels, and ischemic preconditioning in dogs

Am J Physiol

Evidence that late preconditioning against myocardial stunning in conscious rabbits is triggered by the generation of nitric oxide

Circ Res

Heat-shock response is associated with enhanced post ischemic ventricular recovery

Circ Res

Adenosine and the anti-infarct effects of preconditioning

Cardiovasc Res

Cannabinoid receptors and their endogenous agonists

Annu Rev Pharmacol Toxicol

Sarcolemma versus mitochondrial ATP-sensitive K_channels and myocardial preconditioning

Circ Res

Essential role of adenosine, adenosine A1 receptors and ATP-sensitive K_channels in cerebral ischemic preconditioning

Proc Natl Acad Sci USA