<p>Aflatoxin B<sub>1</sub> (AFB<sub>1</sub>) exposure is one of the important factors causing cirrhosis and hepatocellular carcinoma. Selenoproteins, key selenium (Se)-containing biomolecules, may mitigate early AFB<sub>1</sub> hepatotoxicity. To identify hepatic selenoproteins as sensitive biomarkers or functional players in AFB<sub>1</sub> exposure, we allotted 44 11-week-old male C57BL/6J mice into six groups (<i>n</i> = 6–8). Following a five-week pre-feeding period on a 0.03&#xa0;mg Se/kg diet, mice were fed one of three dietary Se levels (0.03, 0.2, or 2.0&#xa0;mg/kg) for six weeks, with daily gavage of 0 or 0.25&#xa0;mg AFB<sub>1</sub>/kg body weight administered during the final week. Analysis of the sampled tissues showed that hepatic mRNA abundances of four selenoproteins (<i>Selenoh</i>, <i>Selenok</i>, <i>Selenos</i>, and <i>Sephs2</i>) and 8-oxoguanine DNA glycosylase (<i>Ogg1</i>) were increased across all three dietary Se levels (<i>P</i> &lt; 0.05). In contrast, mRNA abundances of <i>Gpx1</i>, <i>Selenof</i>, <i>Selenoo</i>, <i>Selenot</i>, <i>Selenow</i>, and <i>Txnrd3</i> were significantly increased at only one or two Se levels (<i>P</i> &lt; 0.05). Notably, <i>Selenoh</i> mRNA abundance positively correlated with dietary Se levels without AFB<sub>1</sub> exposure (<i>R</i><sup><i>2</i></sup> = 0.22, <i>P</i> = 0.04), while <i>Ogg1</i> mRNA abundance negatively correlated with serum 8-hydroxydeoxyguanosine concentrations in the AFB<sub>1</sub>-treated groups (<i>R</i><sup><i>2</i></sup> = 0.19, <i>P</i> = 0.04). Selenoh and Sephs2 protein levels were increased by Se intake (<i>P</i> &lt; 0.05), but not by AFB<sub>1</sub> exposure. Conclusively, hepatic <i>Selenoh</i> mRNA was more sensitive to short-term, low AFB<sub>1</sub> exposure than its protein and showed a positive response to dietary Se intake in mice, emphasizing its potential as a valuable biomarker in assessing the Se-AFB<sub>1</sub> interaction.</p>

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mRNA Rather than Protein Expression of Hepatic Selenoprotein H is More Sensitive to Short-term Low Aflatoxin B1 Exposure in Mice with Varying Selenium Intake

  • Ruirui Yu,
  • Mengru Hao,
  • Aiping Liu,
  • Chenggang Yang,
  • Ping Xu,
  • Yong Zhou,
  • Alexey A. Tinkov,
  • Aolin Yang,
  • Qingqing Lv,
  • Ziyu Han,
  • Chao Wang,
  • Zhou Wang,
  • Jie Jiang,
  • Xiaoling Che,
  • Litao Sun,
  • Ji-Chang Zhou

摘要

Aflatoxin B1 (AFB1) exposure is one of the important factors causing cirrhosis and hepatocellular carcinoma. Selenoproteins, key selenium (Se)-containing biomolecules, may mitigate early AFB1 hepatotoxicity. To identify hepatic selenoproteins as sensitive biomarkers or functional players in AFB1 exposure, we allotted 44 11-week-old male C57BL/6J mice into six groups (n = 6–8). Following a five-week pre-feeding period on a 0.03 mg Se/kg diet, mice were fed one of three dietary Se levels (0.03, 0.2, or 2.0 mg/kg) for six weeks, with daily gavage of 0 or 0.25 mg AFB1/kg body weight administered during the final week. Analysis of the sampled tissues showed that hepatic mRNA abundances of four selenoproteins (Selenoh, Selenok, Selenos, and Sephs2) and 8-oxoguanine DNA glycosylase (Ogg1) were increased across all three dietary Se levels (P < 0.05). In contrast, mRNA abundances of Gpx1, Selenof, Selenoo, Selenot, Selenow, and Txnrd3 were significantly increased at only one or two Se levels (P < 0.05). Notably, Selenoh mRNA abundance positively correlated with dietary Se levels without AFB1 exposure (R2 = 0.22, P = 0.04), while Ogg1 mRNA abundance negatively correlated with serum 8-hydroxydeoxyguanosine concentrations in the AFB1-treated groups (R2 = 0.19, P = 0.04). Selenoh and Sephs2 protein levels were increased by Se intake (P < 0.05), but not by AFB1 exposure. Conclusively, hepatic Selenoh mRNA was more sensitive to short-term, low AFB1 exposure than its protein and showed a positive response to dietary Se intake in mice, emphasizing its potential as a valuable biomarker in assessing the Se-AFB1 interaction.