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

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

doi:10.3390/ph14090863

Beatriz Carmona-Hidalgo, Adela García-Martín + Show 2 more

Open Access

https://doi.org/10.3390/ph14090863

Copy DOI

Abstract

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.

Highlights

Cannabis sativa is one of the most cultivated plants over the years due to its high economical and medical value [1]
Non-fasting blood glucose was elevated after 3 days of STZ treatment in both vehicleSTZ and CBD-STZ-treated mice compared to healthy controls (Figure 1a)
On day 14, non-fasting blood glucose was 1.8-fold and 2.3-fold higher in vehicle-STZ and CBD-STZtreated mice, respectively, compared to control (Figure 1b), and fasting blood glucose was 114 ± 8 mg/dL and 133 ± 26 mg/dL compared to 89 ± 4 mg/dL in healthy control mice (Figure 1c)

Summary

Introduction

Cannabis sativa is one of the most cultivated plants over the years due to its high economical and medical value [1]. C. sativa has a variety of properties, including analgesic [2], antibacterial [3], and antiinflammatory [4] effects among others. The most abundant non-psychotropic cannabinoid from Cannabis sativa is cannabidiol (CBD), which has increased interest for medicinal applications because of its broad biological activity spectrum. The first study about the effectiveness of CBD as an anticonvulsant was carried out by Consroe and Wolking in. 1977 [5], a starting point for further research that demonstrated preclinical-evidences of CDB such as anticonvulsant, antinausea, and analgesic effects [6]. CBD, alone (Epidiolex) or in combination with THC (Sativex), is approved in some countries for the treatment of refractory epilepsy in children and spasticity in multiple sclerosis, 4.0/).

Methods

Results

Conclusion