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



Aryannejad A1, 2 ; Eslami F1, 2 ; Shayan M1, 2 ; Noroozi N1, 2 ; Hedayatyanfard K3, 4 ; Tavangar SM5 ; Jafari RM1 ; Dehpour AR1, 2
Authors
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Authors Affiliations
  1. 1. Department of Pharmacology, Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Physiology and Pharmacology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran
  4. 4. Department of Cardiology, Cardiovascular Research Center, Alborz University of Medical Sciences, Karaj, Iran
  5. 5. Department of Pathology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran

Source: Journal of Reconstructive Microsurgery Published:2023


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. © 2023 Thieme Medical Publishers, Inc.. All rights reserved.
3. The Current State of Knowledge on How to Improve Skin Flap Survival: A Review, Journal of Plastic# Reconstructive and Aesthetic Surgery (2023)
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