Cannabidiol Improves Random-Pattern Skin Flap Survival in Rats: Involvement of Cannabinoid Type-2 Receptors

Abstract

Background One of the major complications associated with random-pattern skin flaps is distal necrosis. Cannabidiol (CBD) has recently gained much attention as a therapeutic anti-inflammatory agent. We aimed to evaluate the efficacy of CBD on the random-pattern skin flap survival (SFS) in rats and to explore the possible involvement of cannabinoid type-2 (CB2) receptors.

Methods In this controlled experimental study, we randomly divided male Wistar rats into seven study groups (six rats each). We performed a random-pattern skin flap model in each rat following pretreatment with vehicle (control) or multiple doses of CBD (0.3, 1, 5, or 10 mg/kg). In a separate group, we injected SR144528 (2 mg/kg), a high affinity and selective CB2 inverse agonist, before the most effective dose of CBD (1 mg/kg). A sham nontreated and nonoperated group was also included. Seven days after surgeries, the percentage of necrotic area (PNA) was calculated. Histopathological microscopy, CB2 expression level, and interleukin (IL)-1β and tumor necrosis factor (TNF)-α concentrations were also investigated in the flap tissue samples.

Results A PNA of 72.7 ± 7.5 (95% confidence interval [CI]: 64.8–80.6) was captured in the control group. Following treatment with CBD 0.3, 1, 5, and 10 mg/kg, a dose-dependent effect was observed with PNAs of 51.0 ± 10.0 (95% CI: 40.5–61.5; p <0.05), 15.4 ± 5.8 (95% CI: 9.3–21.5; p <0.001), 37.1 ± 10.2 (95% CI: 26.3–47.8; p <0.001), and 46.4 ± 14.0 (95% CI: 31.7–61.1; p <0.001), respectively. Histopathologically, tissues enhanced significantly. Besides, CB2 expression surged remarkably, IL-1β and TNF-α concentrations decreased considerably after treatment with CBD of 1 mg/kg compared with the control (p <0.05 and <0.001, respectively). Administering SR144528 reversed the favorable effects of CBD of 1 mg/kg, both macroscopically and microscopically.

Conclusion Pretreatment with CBD of 1 mg/kg improved SFS considerably in rats and exerted desirable anti-inflammatory effects which were possibly mediated by CB2 receptors.

Keywords

cannabidiol - cannabinoid receptors - skin flap - rat - inflammation

Authorship Confirmation

All the authors have read and approved the final draft.

Ethical Approval

The study protocol was approved by the Ethics in Medical Research Committee of Tehran University of Medical Sciences, Tehran, Iran (ethics approval code: IR.TUMS.MEDICINE.REC.1399.1142).

Data Availability

The datasets generated and analyzed during the current study would be available from the corresponding author on reasonable request.

^† Armin Aryannejad and Faezeh Eslami contributed equally to this work as co–first authors.

Publication History

Received: 29 November 2021

Accepted: 22 March 2022

Article published online:
11 July 2022

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