Long-Term Selenium-Deficient Diet Induces Liver Damage by Altering Hepatocyte Ultrastructure and MMP1/3 and TIMP1/3 Expression in Growing Rats

Biol Trace Elem Res. 2017 Feb;175(2):396-404. doi: 10.1007/s12011-016-0781-5. Epub 2016 Jun 24.


The effects of selenium (Se)-deficient diet on the liver were evaluated by using growing rats which were fed with normal and Se-deficient diets, respectively, for 109 days. The results showed that rats fed with Se-deficient diet led to a decrease in Se concentration in the liver, particularly among male rats from the low-Se group. This causes alterations to the ultrastructure of hepatocytes with condensed chromatin and swelling mitochondria observed after low Se intake. Meanwhile, pathological changes and increased fibrosis in hepatic periportal were detected by hematoxylin and eosin and Masson's trichrome staining in low-Se group. Furthermore, through immunohistochemistry (IHC) staining, higher expressions of metalloproteinases (MMP1/3) and their tissue inhibitors of metalloproteinases (TIMP1/3) were observed in the hepatic periportal of rats from the low-Se group. However, higher expressions of MMP1/3 and lower expressions of TIMP1/3 were detected in hepatic central vein and hepatic sinusoid. In addition, upregulated expressions of MMP1/3 and downregulated expressions of TIMP1/3 at the messenger RNA (mRNA) and protein levels also appeared to be relevant to low Se intake. In conclusion, Se-deficient diet could cause low Se concentration in the liver, alterations of hepatocyte ultrastructure, differential expressions of MMP1/3 and TIMP1/3 as well as fibrosis in the liver hepatic periportal.

Keywords: Liver; Low selenium; MMP; Pathological changes; TIMP.

MeSH terms

  • Animals
  • Gene Expression Regulation*
  • Hepatocytes* / metabolism
  • Hepatocytes* / ultrastructure
  • Liver Diseases* / etiology
  • Liver Diseases* / metabolism
  • Liver Diseases* / pathology
  • Liver* / metabolism
  • Liver* / ultrastructure
  • Male
  • Matrix Metalloproteinase 1 / biosynthesis*
  • Matrix Metalloproteinase 3 / biosynthesis*
  • Rats
  • Rats, Sprague-Dawley
  • Selenium / deficiency*
  • Tissue Inhibitor of Metalloproteinase-1 / biosynthesis*
  • Tissue Inhibitor of Metalloproteinase-3 / biosynthesis*


  • TIMP1 protein, rat
  • Tissue Inhibitor of Metalloproteinase-1
  • Tissue Inhibitor of Metalloproteinase-3
  • Matrix Metalloproteinase 3
  • MMP1 protein, rat
  • Matrix Metalloproteinase 1
  • Selenium