Yang Lingchen, Decas Tristan, Zhang Yuhang, Alassane-Kpembi Imourana
Centre de Recherche en Infectiologie Porcine et Avicole (CRIPA), Faculté de Médecine Vétérinaire, Université de Montréal, Saint-Hyacinthe, QC J2S 2M2, Canada.
College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China.
Toxins (Basel). 2025 May 12;17(5):241. doi: 10.3390/toxins17050241.
The deoxynivalenol (DON) mycotoxin poses serious health risks, especially to swine, which are highly susceptible to intestinal damage. Existing strategies to counteract DON toxicity remain insufficient. This study aimed to evaluate the protective effects of cannabidiol (CBD), a phytocannabinoid with anti-inflammatory properties, against DON-induced intestinal toxicity in porcine intestinal epithelial cells. Using differentiated and proliferating porcine intestinal epithelial cells (IPEC-J2), we evaluated CBD (2.5-5 μM) against DON (0.5-50 μM) through viability assays, apoptosis markers (/ ratio), inflammatory mediators (, , ), oxidative stress indicators (, , ), tight junction gene expression (, ), and barrier permeability. DON exhibited dose- and time-dependent cytotoxicity (IC = 2.60 μM at 24 h; 1.07 μM at 48 h). Pre-treatment with 5 μM CBD restored cell viability at low DON concentrations (0.5-2 μM) but failed at ≥8 μM. In differentiated cells, CBD suppressed apoptosis (reduced / ratio), oxidative stress (downregulated ; restored expression), and inflammation (decreased and ) under high-dose DON (50 μM), while enhancing tight junction protein expression and barrier integrity at 5 μM DON. Conversely, in proliferating cells, CBD exacerbated apoptosis (elevated / ratio) and inflammatory responses (upregulated and ) at subtoxic levels of DON (2 μM). CBD alone induced cytotoxicity at ≥10 μM. Our findings demonstrate that CBD exhibits context-dependent efficacy, providing protection in differentiated epithelia under moderate DON exposure (≤5 μM) but exhibiting detrimental effects in proliferating cells. Its narrow therapeutic window and paradoxical actions necessitate cautious application. These findings position CBD as a potential adjunctive therapy for DON detoxification but highlight critical limitations for standalone use.
脱氧雪腐镰刀菌烯醇（DON）霉菌毒素会带来严重的健康风险，尤其是对猪而言，猪对肠道损伤高度敏感。现有的对抗DON毒性的策略仍然不足。本研究旨在评估具有抗炎特性的植物大麻素大麻二酚（CBD）对DON诱导的猪肠道上皮细胞肠道毒性的保护作用。我们使用分化和增殖的猪肠道上皮细胞（IPEC-J2），通过活力测定、凋亡标志物（/比值）、炎症介质（、、）、氧化应激指标（、、）、紧密连接基因表达（、）和屏障通透性，评估了CBD（2.5 - 5 μM）对DON（0.5 - 50 μM）的作用。DON表现出剂量和时间依赖性细胞毒性（24小时时IC = 2.60 μM；48小时时为1.07 μM）。用5 μM CBD预处理可在低DON浓度（0.5 - 2 μM）时恢复细胞活力，但在≥8 μM时则无效。在分化细胞中，在高剂量DON（50 μM）作用下，CBD可抑制凋亡（降低/比值）、氧化应激（下调；恢复表达）和炎症（降低和），而在5 μM DON时可增强紧密连接蛋白表达和屏障完整性。相反，在增殖细胞中，在DON的亚毒性水平（2 μM）下，CBD会加剧凋亡（升高/比值）和炎症反应（上调和）。单独使用CBD在≥10 μM时会诱导细胞毒性。我们的研究结果表明，CBD表现出依赖于环境的功效，在中等DON暴露（≤5 μM）下对分化上皮细胞具有保护作用，但在增殖细胞中表现出有害作用。其狭窄的治疗窗口和矛盾的作用需要谨慎应用。这些发现使CBD成为DON解毒的潜在辅助治疗方法，但也突出了其单独使用的关键局限性。
