Selected phytocannabinoids inhibit SN-38- and cytokine-evoked increases in epithelial permeability and improve intestinal barrier function in vitro

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“Irinotecan use is linked to the development of gastrointestinal toxicity and inflammation, or gastrointestinal mucositis. Selected phytocannabinoids have been ascribed anti-inflammatory effects in models of gastrointestinal inflammation, associated with maintaining epithelial barrier function.

We characterised the mucoprotective capacity of the phytocannabinoids: cannabidiol, cannabigerol, cannabichromene and cannabidivarin in a cell-based model of intestinal epithelial stress occurring in mucositis.

Transepithelial electrical resistance (TEER) was measured to determine changes in epithelial permeability in the presence of SN-38 (5 μM) or the pro-inflammatory cytokines TNFα and IL-1β (each at 100 ng/mL), alone or with concomitant treatment with each of the phytocannabinoids (1 μM). The DCFDA assay was used to determine the ROS-scavenging ability of each phytocannabinoid following treatment with the lipid peroxidant tbhp (200 μM).

Each phytocannabinoid provided significant protection against cytokine-evoked increases in epithelial permeability. Cannabidiol, cannabidivarin and cannabigerol were also able to significantly inhibit SN-38-evoked increases in permeability. None of the tested phytocannabinoids inhibited tbhp-induced ROS generation.

These results highlight a novel role for cannabidiol, cannabidivarin and cannabigerol as inhibitors of SN-38-evoked increases in epithelial permeability and support the rationale for the further development of novel phytocannabinoids as supportive therapeutics in the management of irinotecan-associated mucositis.”

  • “•Phytocannabinoids may have efficacy in alleviating intestinal mucositis
  • •Cannabidiol, cannabidivarin, cannabichromene and cannabigerol (CBG) were tested for effects on intestinal epithelial permeability
  • •Intestinal epithelial Caco-2 cells were exposed to irinotecan metabolite SN-38 or cytokines with or without selected phytocannabinoids
  • •Phytocannabinoids variably protected against cytokine and SN-38-evoked increases in epithelial permeability without antioxidant effects
  • •Minor phytocannabinoids may contribute to mucoprotection and improve epithelial barrier function”

“Irinotecan, sold under the brand name Camptosar among others, is an anti-cancer medication used to treat colon cancer and small cell lung cancer. For colon cancer it is used either alone or with fluorouracil. For small cell lung cancer it is used with cisplatin. It is given intravenously.”,It%20is%20given%20intravenously.

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