Detrimental Effect of Cannabidiol on the Early Onset of Diabetic Nephropathy in Male Mice

Anti-inflammatory and antidiabetogenic properties have been ascribed to cannabidiol (CBD). CBD-based medicinal drugs have been approved for over a lustrum, and a boom in the commercialization of CBD products started in parallel. Herein, we explored the efficacy of CBD in streptozotocin (STZ)-induced...

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Main Authors: Beatriz Carmona-Hidalgo, Adela García-Martín, Eduardo Muñoz, Isabel González-Mariscal
Format: Article
Language:English
Published: MDPI AG 2021-08-01
Series:Pharmaceuticals
Subjects:
Online Access:https://www.mdpi.com/1424-8247/14/9/863
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author Beatriz Carmona-Hidalgo
Adela García-Martín
Eduardo Muñoz
Isabel González-Mariscal
author_facet Beatriz Carmona-Hidalgo
Adela García-Martín
Eduardo Muñoz
Isabel González-Mariscal
author_sort Beatriz Carmona-Hidalgo
collection DOAJ
description Anti-inflammatory and antidiabetogenic properties have been ascribed to cannabidiol (CBD). CBD-based medicinal drugs have been approved for over a lustrum, and a boom in the commercialization of CBD products started in parallel. Herein, we explored the efficacy of CBD in streptozotocin (STZ)-induced diabetic mice to prevent diabetic nephropathy at onset. Eight-to-ten-week-old C57BL6J male mice were treated daily intraperitoneally with 10 mg/kg of CBD or vehicle for 14 days. After 8 days of treatment, mice were challenged with STZ or vehicle (healthy-control). At the end of the study, non-fasting blood glucose (FBG) level was 276 ± 42 mg/dL in vehicle-STZ-treated compared to 147 ± 9 mg/dL (<i>p</i> ≤ 0.01) in healthy-control mice. FBG was 114 ± 8 mg/dL in vehicle-STZ-treated compared to 89 ± 4 mg/dL in healthy-control mice (<i>p</i> ≤ 0.05). CBD treatment did not prevent STZ-induced hyperglycemia, and non-FBG and FBG levels were 341 ± 40 and 133 ± 26 mg/dL, respectively. Additionally, treatment with CBD did not avert STZ-induced glucose intolerance or pancreatic beta cell mass loss compared to vehicle-STZ-treated mice. Anatomopathological examination showed that kidneys from vehicle-STZ-treated mice had a 35% increase of glomerular size compared to healthy-control mice (<i>p</i> ≤ 0.001) and presented lesions with a 43% increase in fibrosis and T cell infiltration (<i>p</i> ≤ 0.001). Although treatment with CBD prevented glomerular hypertrophy and reduced T cell infiltration, it significantly worsened overall renal damage (<i>p</i> ≤ 0.05 compared to vehicle-STZ mice), leading to a more severe renal dysfunction than STZ alone. In conclusion, we showed that CBD could be detrimental for patients with type 1 diabetes, particularly those undergoing complications such as diabetic nephropathy.
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spelling doaj.art-367930f58d464d869c1c8152672177852023-11-22T14:44:32ZengMDPI AGPharmaceuticals1424-82472021-08-0114986310.3390/ph14090863Detrimental Effect of Cannabidiol on the Early Onset of Diabetic Nephropathy in Male MiceBeatriz Carmona-Hidalgo0Adela García-Martín1Eduardo Muñoz2Isabel González-Mariscal3Emerald Health Biotechnology, 14014 Córdoba, SpainEmerald Health Biotechnology, 14014 Córdoba, SpainInstituto Maimónides de Investigación Biomédica de Córdoba, Departamento de Biología Celular, Fisiología e Inmunología, Universidad de Córdoba, Hospital Universitario Reina Sofía, 14004 Córdoba, SpainInstituto de Investigación Biomédica de Málaga-IBIMA, UGC Endocrinología y Nutrición, Hospital Regional Universitario de Málaga, 29009 Málaga, SpainAnti-inflammatory and antidiabetogenic properties have been ascribed to cannabidiol (CBD). CBD-based medicinal drugs have been approved for over a lustrum, and a boom in the commercialization of CBD products started in parallel. Herein, we explored the efficacy of CBD in streptozotocin (STZ)-induced diabetic mice to prevent diabetic nephropathy at onset. Eight-to-ten-week-old C57BL6J male mice were treated daily intraperitoneally with 10 mg/kg of CBD or vehicle for 14 days. After 8 days of treatment, mice were challenged with STZ or vehicle (healthy-control). At the end of the study, non-fasting blood glucose (FBG) level was 276 ± 42 mg/dL in vehicle-STZ-treated compared to 147 ± 9 mg/dL (<i>p</i> ≤ 0.01) in healthy-control mice. FBG was 114 ± 8 mg/dL in vehicle-STZ-treated compared to 89 ± 4 mg/dL in healthy-control mice (<i>p</i> ≤ 0.05). CBD treatment did not prevent STZ-induced hyperglycemia, and non-FBG and FBG levels were 341 ± 40 and 133 ± 26 mg/dL, respectively. Additionally, treatment with CBD did not avert STZ-induced glucose intolerance or pancreatic beta cell mass loss compared to vehicle-STZ-treated mice. Anatomopathological examination showed that kidneys from vehicle-STZ-treated mice had a 35% increase of glomerular size compared to healthy-control mice (<i>p</i> ≤ 0.001) and presented lesions with a 43% increase in fibrosis and T cell infiltration (<i>p</i> ≤ 0.001). Although treatment with CBD prevented glomerular hypertrophy and reduced T cell infiltration, it significantly worsened overall renal damage (<i>p</i> ≤ 0.05 compared to vehicle-STZ mice), leading to a more severe renal dysfunction than STZ alone. In conclusion, we showed that CBD could be detrimental for patients with type 1 diabetes, particularly those undergoing complications such as diabetic nephropathy.https://www.mdpi.com/1424-8247/14/9/863cannabinoidstreptozotocinphytocannabinoidtype 1 diabetesendocannabinoid systemchronic kidney disease
spellingShingle Beatriz Carmona-Hidalgo
Adela García-Martín
Eduardo Muñoz
Isabel González-Mariscal
Detrimental Effect of Cannabidiol on the Early Onset of Diabetic Nephropathy in Male Mice
Pharmaceuticals
cannabinoid
streptozotocin
phytocannabinoid
type 1 diabetes
endocannabinoid system
chronic kidney disease
title Detrimental Effect of Cannabidiol on the Early Onset of Diabetic Nephropathy in Male Mice
title_full Detrimental Effect of Cannabidiol on the Early Onset of Diabetic Nephropathy in Male Mice
title_fullStr Detrimental Effect of Cannabidiol on the Early Onset of Diabetic Nephropathy in Male Mice
title_full_unstemmed Detrimental Effect of Cannabidiol on the Early Onset of Diabetic Nephropathy in Male Mice
title_short Detrimental Effect of Cannabidiol on the Early Onset of Diabetic Nephropathy in Male Mice
title_sort detrimental effect of cannabidiol on the early onset of diabetic nephropathy in male mice
topic cannabinoid
streptozotocin
phytocannabinoid
type 1 diabetes
endocannabinoid system
chronic kidney disease
url https://www.mdpi.com/1424-8247/14/9/863
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