Cannabidiol Mitigates Deoxynivalenol-Induced Intestinal Toxicity by Regulating Inflammation, Oxidative Stress, and Barrier Integrity
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...
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2025-05-01
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| author | Lingchen Yang Tristan Decas Yuhang Zhang Imourana Alassane-Kpembi |
| author_facet | Lingchen Yang Tristan Decas Yuhang Zhang Imourana Alassane-Kpembi |
| author_sort | Lingchen Yang |
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| description | 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 (<i>Bax</i>/<i>Bcl-2</i> ratio), inflammatory mediators (<i>NFκB</i>, <i>IL-6</i>, <i>COX-2</i>), oxidative stress indicators (<i>TXNIP</i>, <i>SOD1</i>, <i>CAT</i>), tight junction gene expression (<i>Claudin-1</i>, <i>Occludin</i>), and barrier permeability. DON exhibited dose- and time-dependent cytotoxicity (IC<sub>50</sub> = 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 <i>Bax</i>/<i>Bcl-2</i> ratio), oxidative stress (downregulated <i>TXNIP</i>; restored <i>CAT</i> expression), and inflammation (decreased <i>IL-6</i> and <i>COX-2</i>) 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 <i>Bax</i>/<i>Bcl-2</i> ratio) and inflammatory responses (upregulated <i>IL-6</i> and <i>COX-2</i>) 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. |
| format | Article |
| id | doaj-art-48e06d66a00f4b61827d20b8a98d4114 |
| institution | Kabale University |
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| spelling | doaj-art-48e06d66a00f4b61827d20b8a98d41142025-08-20T03:47:58ZengMDPI AGToxins2072-66512025-05-0117524110.3390/toxins17050241Cannabidiol Mitigates Deoxynivalenol-Induced Intestinal Toxicity by Regulating Inflammation, Oxidative Stress, and Barrier IntegrityLingchen Yang0Tristan Decas1Yuhang Zhang2Imourana Alassane-Kpembi3Centre de Recherche en Infectiologie Porcine et Avicole (CRIPA), Faculté de Médecine Vétérinaire, Université de Montréal, Saint-Hyacinthe, QC J2S 2M2, CanadaCentre de Recherche en Infectiologie Porcine et Avicole (CRIPA), Faculté de Médecine Vétérinaire, Université de Montréal, Saint-Hyacinthe, QC J2S 2M2, CanadaCentre de Recherche en Infectiologie Porcine et Avicole (CRIPA), Faculté de Médecine Vétérinaire, Université de Montréal, Saint-Hyacinthe, QC J2S 2M2, CanadaCentre de Recherche en Infectiologie Porcine et Avicole (CRIPA), Faculté de Médecine Vétérinaire, Université de Montréal, Saint-Hyacinthe, QC J2S 2M2, CanadaThe 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 (<i>Bax</i>/<i>Bcl-2</i> ratio), inflammatory mediators (<i>NFκB</i>, <i>IL-6</i>, <i>COX-2</i>), oxidative stress indicators (<i>TXNIP</i>, <i>SOD1</i>, <i>CAT</i>), tight junction gene expression (<i>Claudin-1</i>, <i>Occludin</i>), and barrier permeability. DON exhibited dose- and time-dependent cytotoxicity (IC<sub>50</sub> = 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 <i>Bax</i>/<i>Bcl-2</i> ratio), oxidative stress (downregulated <i>TXNIP</i>; restored <i>CAT</i> expression), and inflammation (decreased <i>IL-6</i> and <i>COX-2</i>) 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 <i>Bax</i>/<i>Bcl-2</i> ratio) and inflammatory responses (upregulated <i>IL-6</i> and <i>COX-2</i>) 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.https://www.mdpi.com/2072-6651/17/5/241deoxynivalenolcannabidiolintestinal epithelial cellsoxidative stressdose-dependent effects |
| spellingShingle | Lingchen Yang Tristan Decas Yuhang Zhang Imourana Alassane-Kpembi Cannabidiol Mitigates Deoxynivalenol-Induced Intestinal Toxicity by Regulating Inflammation, Oxidative Stress, and Barrier Integrity Toxins deoxynivalenol cannabidiol intestinal epithelial cells oxidative stress dose-dependent effects |
| title | Cannabidiol Mitigates Deoxynivalenol-Induced Intestinal Toxicity by Regulating Inflammation, Oxidative Stress, and Barrier Integrity |
| title_full | Cannabidiol Mitigates Deoxynivalenol-Induced Intestinal Toxicity by Regulating Inflammation, Oxidative Stress, and Barrier Integrity |
| title_fullStr | Cannabidiol Mitigates Deoxynivalenol-Induced Intestinal Toxicity by Regulating Inflammation, Oxidative Stress, and Barrier Integrity |
| title_full_unstemmed | Cannabidiol Mitigates Deoxynivalenol-Induced Intestinal Toxicity by Regulating Inflammation, Oxidative Stress, and Barrier Integrity |
| title_short | Cannabidiol Mitigates Deoxynivalenol-Induced Intestinal Toxicity by Regulating Inflammation, Oxidative Stress, and Barrier Integrity |
| title_sort | cannabidiol mitigates deoxynivalenol induced intestinal toxicity by regulating inflammation oxidative stress and barrier integrity |
| topic | deoxynivalenol cannabidiol intestinal epithelial cells oxidative stress dose-dependent effects |
| url | https://www.mdpi.com/2072-6651/17/5/241 |
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