Abstract
BackgroundThe endocannabinoid CB1 receptor is known to have protective effects in kidney disease. The aim of the present study is to evaluate the potential agonistic and antagonistic actions and to determine the renoprotective potential of CB1 receptors in diabetic nephropathy. The present work investigates the possible role of CB1 receptors in the pathogenesis of diabetes-induced nephropathy. Streptozotocin (STZ) (55 mg/kg, i.p., once) is administered to uninephrectomised rats for induction of experimental diabetes mellitus. The CB1 agonist (oleamide) and CB1 antagonist (AM6545) treatment were initiated in diabetic rats after 1 week of STZ administration and were given for 24 weeks.ResultsThe progress in diabetic nephropathy is estimated biochemically by measuring serum creatinine (1.28±0.03) (p < 0.005), blood urea nitrogen (67.6± 2.10) (p < 0.001), urinary microprotein (74.62± 3.47) (p < 0.005) and urinary albuminuria (28.31±1.17) (p < 0.0001). Renal inflammation was assessed by estimating serum levels of tumor necrosis factor alpha (75.69±1.51) (p < 0.001) and transforming growth factor beta (8.73±0.31) (p < 0.001). Renal morphological changes were assessed by estimating renal hypertrophy (7.38± 0.26) (p < 0.005) and renal collagen content (10.42± 0.48) (p < 0.001).ConclusionsFrom the above findings, it can be said that diabetes-induced nephropathy may be associated with overexpression of CB1 receptors and blockade of CB1 receptors might be beneficial in ameliorating the diabetes-induced nephropathy.Graphical abstract
Highlights
The endocannabinoid CB1 receptor is known to have protective effects in kidney disease
Uninephrectomized diabetic rats treated with oleamide 1 mg/kg and 2.5 mg/kg had no effect on serum creatinine
The uninephrectomized diabetic rats treated with AM6545 (16 mg/kg, i.p.) showed a significant decrease in serum creatinine levels compared to low dose (4 mg/ kg and 8 mg/kg) of AM-6545 as shown in Fig. 1 (p< 0.005, p
Summary
The endocannabinoid CB1 receptor is known to have protective effects in kidney disease. The aim of the present study is to evaluate the potential agonistic and antagonistic actions and to determine the renoprotective potential of CB1 receptors in diabetic nephropathy. The present work investigates the possible role of CB1 receptors in the pathogenesis of diabetes-induced nephropathy. The CB1 agonist (oleamide) and CB1 antagonist (AM6545) treatment were initiated in diabetic rats after 1 week of STZ administration and were given for 24 weeks. Due to the complexity of primary signalling culprits involved in the DN disease pathogenesis, very few therapeutic choices are presently available. ECS is a lipid signalling arrangement comprises of cannabinoid receptors along with lipid ligands and machinery of enzymes [6]. Endocannabinoids are the products of arachidonic acid, resembling supplementary fat transmitters (eicosanoids like prostaglandins or leukotrienes) [7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
