Role of endocannabinoid CB1 receptors in Streptozotocin-induced uninephrectomised Wistar rats in diabetic nephropathy

Abstract Background 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...

Full description

Bibliographic Details
Main Authors: Jayarami Reddy Medapati, Deepthi Rapaka, Veera Raghavulu Bitra, Santhosh Kumar Ranajit, Girija Sankar Guntuku, Annapurna Akula
Format: Article
Language:English
Published: SpringerOpen 2021-05-01
Series:Beni-Suef University Journal of Basic and Applied Sciences
Subjects:
Online Access:https://doi.org/10.1186/s43088-021-00121-y
_version_ 1818641486889091072
author Jayarami Reddy Medapati
Deepthi Rapaka
Veera Raghavulu Bitra
Santhosh Kumar Ranajit
Girija Sankar Guntuku
Annapurna Akula
author_facet Jayarami Reddy Medapati
Deepthi Rapaka
Veera Raghavulu Bitra
Santhosh Kumar Ranajit
Girija Sankar Guntuku
Annapurna Akula
author_sort Jayarami Reddy Medapati
collection DOAJ
description Abstract Background 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. 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. Results The 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). Conclusions From 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
first_indexed 2024-12-16T23:27:56Z
format Article
id doaj.art-66f7f9ad6c834785b6bd97ddb1e3ed55
institution Directory Open Access Journal
issn 2314-8543
language English
last_indexed 2024-12-16T23:27:56Z
publishDate 2021-05-01
publisher SpringerOpen
record_format Article
series Beni-Suef University Journal of Basic and Applied Sciences
spelling doaj.art-66f7f9ad6c834785b6bd97ddb1e3ed552022-12-21T22:11:56ZengSpringerOpenBeni-Suef University Journal of Basic and Applied Sciences2314-85432021-05-0110111210.1186/s43088-021-00121-yRole of endocannabinoid CB1 receptors in Streptozotocin-induced uninephrectomised Wistar rats in diabetic nephropathyJayarami Reddy Medapati0Deepthi Rapaka1Veera Raghavulu Bitra2Santhosh Kumar Ranajit3Girija Sankar Guntuku4Annapurna Akula5A U College of Pharmaceutical Sciences, Andhra UniversityA U College of Pharmaceutical Sciences, Andhra UniversityA U College of Pharmaceutical Sciences, Andhra UniversityPharmacology Division, Vignan Institute of Pharmacuetical TechnologyA U College of Pharmaceutical Sciences, Andhra UniversityA U College of Pharmaceutical Sciences, Andhra UniversityAbstract Background 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. 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. Results The 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). Conclusions From 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 abstracthttps://doi.org/10.1186/s43088-021-00121-yDiabetic nephropathyAlbuminuriaUninephrectomyOleamide
spellingShingle Jayarami Reddy Medapati
Deepthi Rapaka
Veera Raghavulu Bitra
Santhosh Kumar Ranajit
Girija Sankar Guntuku
Annapurna Akula
Role of endocannabinoid CB1 receptors in Streptozotocin-induced uninephrectomised Wistar rats in diabetic nephropathy
Beni-Suef University Journal of Basic and Applied Sciences
Diabetic nephropathy
Albuminuria
Uninephrectomy
Oleamide
title Role of endocannabinoid CB1 receptors in Streptozotocin-induced uninephrectomised Wistar rats in diabetic nephropathy
title_full Role of endocannabinoid CB1 receptors in Streptozotocin-induced uninephrectomised Wistar rats in diabetic nephropathy
title_fullStr Role of endocannabinoid CB1 receptors in Streptozotocin-induced uninephrectomised Wistar rats in diabetic nephropathy
title_full_unstemmed Role of endocannabinoid CB1 receptors in Streptozotocin-induced uninephrectomised Wistar rats in diabetic nephropathy
title_short Role of endocannabinoid CB1 receptors in Streptozotocin-induced uninephrectomised Wistar rats in diabetic nephropathy
title_sort role of endocannabinoid cb1 receptors in streptozotocin induced uninephrectomised wistar rats in diabetic nephropathy
topic Diabetic nephropathy
Albuminuria
Uninephrectomy
Oleamide
url https://doi.org/10.1186/s43088-021-00121-y
work_keys_str_mv AT jayaramireddymedapati roleofendocannabinoidcb1receptorsinstreptozotocininduceduninephrectomisedwistarratsindiabeticnephropathy
AT deepthirapaka roleofendocannabinoidcb1receptorsinstreptozotocininduceduninephrectomisedwistarratsindiabeticnephropathy
AT veeraraghavulubitra roleofendocannabinoidcb1receptorsinstreptozotocininduceduninephrectomisedwistarratsindiabeticnephropathy
AT santhoshkumarranajit roleofendocannabinoidcb1receptorsinstreptozotocininduceduninephrectomisedwistarratsindiabeticnephropathy
AT girijasankarguntuku roleofendocannabinoidcb1receptorsinstreptozotocininduceduninephrectomisedwistarratsindiabeticnephropathy
AT annapurnaakula roleofendocannabinoidcb1receptorsinstreptozotocininduceduninephrectomisedwistarratsindiabeticnephropathy