The Protective Effect of Heme Oxygenase-1 on Liver Injury Caused by DON-Induced Oxidative Stress and Cytotoxicity

Abstract

Deoxynivalenol (DON) is a kind of Fusarium toxin that can cause a variety of toxic effects. Oxidative stress and DNA damage play a critical role in the toxicity of DON. However, previous studies focused more on acute toxicity in vivo/vitro models and lacked subchronic toxicity study in vivo. The potentially harmful effect of DON given at doses comparable to the daily human consumption in target organs, especially the liver, which is the main detoxification organ of DON, is also still not fully understood. Otherwise, Heme Oxygenase-1 (HO-1) has also reduced cell damage under the DON condition according to our previous study. Therefore, we used a rodent model that mimicked daily human exposure to DON and further explored its mechanism of toxic effects on liver tissue and Hepa 1–6 cell line. We also used adeno-associated virus (AAV)-modified HO-1 expressing by tail vein injection and constructed lentivirus-Hepa 1–6 cell line for mimicking HO-1 protective ability under the DON condition. The main results showed that both 30 d and 90 d exposures of DON could cause low-grade inflammatory infiltration around hepatic centrilobular veins. The reactive oxygen species (ROS) and 8-hydroxy-2 deoxyguanosine (8-OHdG) increased during DON exposure, indicating oxidation stress and DNA damage. Significantly, AAV-mediated liver-specific overexpression of HO-1 reduced DON-induced liver damage and indirectly protected the abilities of antioxidant enzyme/DNA damage repair system, while AAV-mediated silence of HO-1 produced the opposite effect. In addition, we found that overexpression of HO-1 could enhance autophagy and combined it with an antioxidant enzyme/DNA damage repair system to inhibit DON-induced hepatocyte damage. Altogether, these data suggest that HO-1 reduces the oxidative stress and DNA damage caused by DON sub-chronic exposure through maintaining DNA repair, antioxidant activity, as well as autophagy.

Analysis of the Roles of the ISLR2 Gene in Regulating the Toxicity of Zearalenone Exposure in Porcine Intestinal Epithelial Cells

“…Previous studies have reported that SelS overexpression mitigates OTA-induced cytotoxicity and apoptosis [21]. In addition, overexpression of HO-1 reduces the DON-induced ROS and DNA damage by maintaining DNA repair, antioxidant activity, and autophagy [22]. In this study, we observed that ISLR2 overexpression significantly increased the cell viability and reduced the ROS levels of cells exposed to ZEN, indicating the potential of ISLR2 as a molecular target for controlling ZEN-induced toxicity.…”

Loss of CFTR function in macrophages alters the cell transcriptional program and delays lung resolution of inflammation

“…Mac-CF MDM exhibited down-regulation of Prdx1 , 5 , and 6 that encode peroxiredoxins for the metabolism of hydrogen peroxide, and down-regulation of the Heme oxygenase-1 gene Hmox1 ( Figures 6H, I ). HMOX expression has been previously found to be important in response to ROS and ROS-induced DNA damage ( 75 , 76 ). Peroxiredoxins are known to be important for the metabolism of hydrogen peroxide ( 77 , 78 ).…”

Lactoferrin Relieves Deoxynivalenol-Induced Oxidative Stress and Inflammatory Response by Modulating the Nrf2/MAPK Pathways in the Liver

“…It is a secondary metabolite toxin mainly produced by Fusarium graminearum and Fusarium flavus . DON contamination affects multiple organs of mammalians, including disruption of intestinal barrier integrity, destruction of antioxidant/oxidative balance, and alternation of the immune response. , As the metabolic hub of the body, the liver plays a critical role in protein synthesis, lipid metabolism, bile synthesis, and detoxification of harmful substances produced by internal metabolism or external factors. , Recent studies have underscored the liver as one of most targeted organs for DON. , Therefore, more attention should be devoted to the hepatotoxicity caused by DON.…”