Carmona-Hidalgo, BeatrizGarcía-Martín, AdelaMuñoz, EduardoGonzález-Mariscal, Isabel2022-10-192022-10-192021-08-28Carmona-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):863http://hdl.handle.net/10668/4264Anti-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.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/CannabinoidStreptozotocinPhytocannabinoidType 1 diabetesEndocannabinoid systemChronic kidney diseaseCannabinoidesDiabetes Mellitus experimentalDiabetes Mellitus tipo 1EndocannabinoidesInsuficiencia renal crónicaMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::MiceMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Nitroso Compounds::Nitrosourea Compounds::StreptozocinMedical Subject Headings::Diseases::Endocrine System Diseases::Diabetes Mellitus::Diabetes Complications::Diabetic NephropathiesMedical Subject Headings::Diseases::Endocrine System Diseases::Diabetes Mellitus::Diabetes Mellitus, ExperimentalMedical Subject Headings::Chemicals and Drugs::Carbohydrates::Monosaccharides::Hexoses::Glucose::Blood GlucoseMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Terpenes::Cannabinoids::CannabidiolMedical Subject Headings::Diseases::Endocrine System Diseases::Diabetes Mellitus::Diabetes Mellitus, Type 1Medical Subject Headings::Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Hyperglycemia::Glucose IntoleranceMedical Subject Headings::Anatomy::Digestive System::Pancreas::Islets of Langerhans::Insulin-Secreting CellsMedical Subject Headings::Anatomy::Urogenital System::Urinary Tract::KidneyMedical Subject Headings::Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Hyperglycemiaresearch article34577563open access10.3390/ph140908631999-4923PMC8466593