Alteration of Trace Elements during Pathogenesis of N-Nitrosodimethylamine Induced Hepatic Fibrosis

Sci Rep. 2019 Jan 24;9(1):708. doi: 10.1038/s41598-018-37516-4.


The biochemical abnormalities and oxidative stress during pathogenesis of hepatic fibrosis could lead to alteration of trace elements. We studied the alteration of major trace elements during the pathogenesis of N-nitrosodimethylamine (NDMA)-induced hepatic fibrosis in rats. The biochemical and pathological indices of liver functions and hepatic fibrosis were evaluated. Serum and liver levels of copper, iron and zinc were determined using atomic absorption spectrophotometry. Cobalt, manganese, and molybdenum in the serum and liver were estimated by inductively coupled plasma mass spectrometry. Serial administrations of NDMA resulted in decreased serum albumin, biochemical abnormalities, increase of total liver collagen, and well-developed fibrosis and early cirrhosis. Serum and liver zinc content significantly decreased on all the days following NDMA administration. When copper and molybdenum markedly increased in the serum, liver molybdenum decreased dramatically. Both iron and manganese content significantly increased in the liver following NDMA-induced fibrosis. The results of the present study indicate that alteration of trace elements during pathogenesis of hepatic fibrosis is due to metabolic imbalance, biochemical abnormalities, decreased serum albumin, and ascites following NDMA-induced liver injury. The modulation of trace elements during hepatic fibrosis could play a prominent role in progression of the disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / analysis*
  • Biomarkers / metabolism
  • Dimethylnitrosamine / toxicity*
  • Liver Cirrhosis / chemically induced
  • Liver Cirrhosis / metabolism*
  • Liver Cirrhosis / pathology*
  • Liver Function Tests
  • Male
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Wistar
  • Trace Elements / analysis*
  • Trace Elements / metabolism*


  • Biomarkers
  • Trace Elements
  • Dimethylnitrosamine