Selected phytocannabinoids inhibit SN-38- and cytokine-evoked increases in epithelial permeability and improve intestinal barrier function in vitro.
Toxicol In Vitro
; 99: 105888, 2024 Aug.
Article
em En
| MEDLINE
| ID: mdl-38950639
ABSTRACT
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-1ß (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.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Permeabilidade
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Canabidiol
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Canabinoides
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Espécies Reativas de Oxigênio
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Irinotecano
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Mucosa Intestinal
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article