Toxicity of DON on GPx1-Overexpressed or Knockdown Porcine Splenic Lymphocytes In Vitro and Protective Effects of Sodium Selenite

Abstract

Deoxynivalenol (DON) is a common contaminant of grain worldwide and is often detected in the human diet and animal feed. Selenium is an essential trace element in animals. It has many biological functions. The role of selenium in the body is mainly orchestrated by selenoprotein. Glutathione peroxidase (GPx) also exists widely in the body and has attracted much attention due to its high antioxidant capacity. In order to explore the effect of the GPx1 gene on toxicity of DON, in this study, we overexpressed or knockdown GPx1 in porcine splenic lymphocytes, then added different concentrations of DON (0.1025, 0.205, 0.41, and 0.82 μg/mL) and sodium selenite (2 μmol/L) to the culture system. Using various techniques, we detected antioxidant function, free radical content, cell apoptosis, and methylation-related gene expression to explore the effect of GPx1 expression on DON-induced cell damage. We also explored whether selenium can antagonize the toxicity of DON in these two cell models and revealed the protective effect of sodium selenite on DON-induced cell damage in GPx1-overexpressing or knockdown splenic lymphocytes. Finally, our findings revealed the following: (1) GPx1 can regulate the antioxidant capacity, apoptosis rate, and expression of DNA methylation-related genes in pig splenic lymphocytes. (2) Na2SeO3 (2 μmol/L) can regulate the antioxidant capacity, apoptosis rate, and expression of DNA methylation-related genes in pig splenic lymphocytes, and this effect is more significant in GPx1-overexpressing cells than in GPx1-knockdown cells. (3) DON can cause oxidative damage, apoptosis, and methylation injury in GPx1-overexpressing or knockdown pig splenic lymphocytes in a concentration-dependent manner. (4) Na2SeO3 (2 μmol/L) can antagonize the toxic effect of DON on GPx1-overexpressing or knockdown pig splenic lymphocytes. Our findings may have important implications for food/feed safety, human health, and environmental protection.

Disturbances in Thyroid Hormone Metabolism in Rats Exposed to γ- Radiation and Carbon Tetrachloride: The Role of N- acetyl cysteine and Sodium Selenite

“…Since, Se is considered an essential part of different antioxidant enzymes, such as GPx and thioredoxin , it plays an important role in the antioxidant defense mechanisms in the body. An in vitro study showed that sodium selenite could regulate the antioxidant capacity, apoptosis rate, and expression of DNA methylation-related genes in pig splenic lymphocytes (Ren et al, 2019).…”

Effects of Antioxidant Gene Overexpression on Stress Resistance and Malignization In Vitro and In Vivo: A Review

“…The main aim of this review was to systemize and sum up the available studies covering the effects of antioxidant defense gene overexpression on cell resistance to oxidative stress. We analyzed 166 such works [ 20 , 51 , 56 , 58 , 62 , 65 , 66 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 ,…”

“…Increased resistance: UVB [96], deoxynivalenol [97], cisplatin [99,103,105], X-ray [100], doxorubicin [106], H 2 O 2 , GSH high concentration [107] Decreased resistance: cisplatin [103], gemcitabine [104] in vivo Increased resistance: ischemia-reperfusion injury [98], cocaine [101], microcystin-leucine-arginine [102] GPX2 in vitro Increased resistance: cisplatin [108] GPX3 in vitro Increased resistance: ascorbate [109], cisplatin [110], NAPQI [111] GPX4 in vitro…”

Dietary exposure of deoxynivalenol affected cytochrome P450 and growth related-gene expression via DNA methylation in piglet liver

“…It was found that 10 mM DON increased the percentage of 5-methylcytosine in DNA from 4.5-9% in Caco-2 cells [59]. However, another study reported that DON at 3 mg/kg decreased the expression of methyltransferases and upregulated methyl-CpGbinding domain 2 (MBD2) expression in porcine splenic lymphocytes [60]. Abnormal changes in DNA methylation are common in tumorigenesis [61].…”