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

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2021-08-28

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Carmona-Hidalgo, Beatriz
García-Martín, Adela
Muñoz, Eduardo
González-Mariscal, Isabel

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MDPI
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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 (p ≤ 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 (p ≤ 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 (p ≤ 0.001) and presented lesions with a 43% increase in fibrosis and T cell infiltration (p ≤ 0.001). Although treatment with CBD prevented glomerular hypertrophy and reduced T cell infiltration, it significantly worsened overall renal damage (p ≤ 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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Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice
Medical Subject Headings::Organisms::Eukaryota::Animals
Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Nitroso Compounds::Nitrosourea Compounds::Streptozocin
Medical Subject Headings::Diseases::Endocrine System Diseases::Diabetes Mellitus::Diabetes Complications::Diabetic Nephropathies
Medical Subject Headings::Diseases::Endocrine System Diseases::Diabetes Mellitus::Diabetes Mellitus, Experimental
Medical Subject Headings::Chemicals and Drugs::Carbohydrates::Monosaccharides::Hexoses::Glucose::Blood Glucose
Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Terpenes::Cannabinoids::Cannabidiol
Medical Subject Headings::Diseases::Endocrine System Diseases::Diabetes Mellitus::Diabetes Mellitus, Type 1
Medical Subject Headings::Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Hyperglycemia::Glucose Intolerance
Medical Subject Headings::Anatomy::Digestive System::Pancreas::Islets of Langerhans::Insulin-Secreting Cells
Medical Subject Headings::Anatomy::Urogenital System::Urinary Tract::Kidney
Medical Subject Headings::Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Hyperglycemia

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Keywords

Cannabinoid, Streptozotocin, Phytocannabinoid, Type 1 diabetes, Endocannabinoid system, Chronic kidney disease, Cannabinoides, Diabetes Mellitus experimental, Diabetes Mellitus tipo 1, Endocannabinoides, Insuficiencia renal crónica

Citation

Carmona-Hidalgo B, García-Martín A, Muñoz E, González-Mariscal I. Detrimental Effect of Cannabidiol on the Early Onset of Diabetic Nephropathy in Male Mice. Pharmaceuticals. 2021 Aug 28;14(9):863