Abstract
Extensive research has revealed the association of continued oxidative stress with chronic inflammation, which could subsequently affect many different chronic diseases. The mycotoxin deoxynivalenol (DON) frequently contaminates cereals crops worldwide, and are a public health concern since DON ingestion may result in persistent intestinal inflammation. There has also been considerable attention over the potential of DON to provoke oxidative stress. In this study, the cytoprotective effect of Schisandrin A (Sch A), one of the most abundant active dibenzocyclooctadiene lignans in the fruit of Schisandra chinensis (Turcz.) Baill (also known as Chinese magnolia-vine), was investigated in HT-29 cells against DON-induced cytotoxicity, oxidative stress and inflammation. Sch A appeared to protect against DON-induced cytotoxicity in HT-29 cells, and significantly lessened the DON-stimulated intracellular reactive oxygen species and nitrogen oxidative species production. Furthermore, Sch A lowered DON-induced catalase, superoxide dismutase and glutathione peroxidase antioxidant enzyme activities but maintains glutathione S transferase activity and glutathione levels. Mechanistic studies suggest that Sch A reduced DON-induced oxidative stress by down-regulating heme oxygenase-1 expression via nuclear factor (erythroid-derived 2)-like 2 signalling pathway. In addition, Sch A decreased the DON-induced cyclooxygenase-2 expression and prostaglandin E2 production and pro-inflammatory cytokine interleukin 8 expression and secretion. This may be mediated by preventing DON-induced translocation of nuclear factor-κB, as well as activation of mitogen-activated protein kinases pathways. In the light of these findings, we concluded that Sch A exerted a cytoprotective role in DON-induced toxicity in vitro, and it would be valuable to examine in vivo effects.
Highlights
Extensive research has revealed the association of continued oxidative stress with chronic inflammation, which could subsequently affect many different chronic diseases
It was reported that DON led to inflammation and exacerbate inflammatory response in non-cancerous intestinal epithelial cells (IEC-6) following exposure to lipopolysaccharide (LPS) and interferon (IFN)γ, by increasing production of tumor necrosis factor (TNF)α, formation of nitrotyrosine, release of reactive oxygen species (ROS), up-regulating inducible nitric oxide synthase and cyclooxygenase-2 (COX-2) expression, as well as activating nuclear factor κB (NF-κB), nuclear factor-like 2 (Nrf2) and inflammasome[21]
Since Schisandrin A (Sch A) caused a better cytoprotective effect at 1 μM DON concentration, further experiments were carried out with different concentrations of Sch A (2.5–10 μM) pre-treatment followed by DON exposure at 1 μM
Summary
Extensive research has revealed the association of continued oxidative stress with chronic inflammation, which could subsequently affect many different chronic diseases. It was reported that DON led to inflammation and exacerbate inflammatory response in non-cancerous intestinal epithelial cells (IEC-6) following exposure to lipopolysaccharide (LPS) and interferon (IFN)γ, by increasing production of tumor necrosis factor (TNF)α, formation of nitrotyrosine, release of ROS, up-regulating inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression, as well as activating NF-κB, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and inflammasome[21]. Our previous laboratory data has revealed that physiologically relevant concentrations of DON can increase several pro-inflammatory cytokine mRNA levels in a porcine jejunal epithelial cell line[22] Taken together, this suggests that DON could cause persistent intestinal inflammation and this may predispose to various intestinal inflammatory diseases including IBD
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
