Metabolism of N-nitrosodimethylamine, methylation of macromolecules, and development of hepatic fibrosis in rodent models

J Mol Med (Berl). 2020 Sep;98(9):1203-1213. doi: 10.1007/s00109-020-01950-7. Epub 2020 Jul 14.

Abstract

Hepatic fibrosis and cirrhosis are chronic diseases affecting liver and a major health problem throughout the world. The hallmark of fibrosis and cirrhosis is inordinate synthesis and deposition of fibril forming collagens in the extracellular matrix of the liver leading to nodule formation and loss of normal architecture. Hepatic stellate cells play a crucial role in the pathogenesis and progression of liver fibrosis through secretion of several potent fibrogenic factors that trigger hepatocytes, portal fibrocytes, and bone marrow-derived fibroblasts to synthesize and deposit several connective tissue proteins, especially collagens between hepatocytes and space of Disse. Regulation of various events involved in the activation and transformation of hepatic stellate cells seems to be an appropriate strategy for the arrest of hepatic fibrosis and liver cirrhosis. In order to unravel the molecular mechanisms involved in the pathogenesis and progression of hepatic fibrosis, to determine proper and potent targets to arrest fibrosis, and to discover powerful therapeutic agents, a quick and reproducible animal model of hepatic fibrosis and liver cirrhosis that display all decompensating features of human condition is required. This review thoroughly evaluates the biochemical, histological, and pathological features of N-nitrosodimethylamine-induced model of liver injury, hepatic fibrosis, and early cirrhosis in rodents.

Keywords: Dimethylnitrosamine; Hepatic fibrosis; Liver cirrhosis; N-Nitrosodimethylamine; NDMA; Rodent model.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Dimethylnitrosamine / adverse effects*
  • Disease Models, Animal
  • Disease Susceptibility
  • Fibroblasts
  • Fibrosis
  • Hepatic Stellate Cells / metabolism
  • Hepatocytes / metabolism
  • Hepatocytes / pathology
  • Humans
  • Liver Cirrhosis / etiology*
  • Liver Cirrhosis / metabolism*
  • Liver Cirrhosis / pathology
  • Macromolecular Substances / metabolism*
  • Methylation
  • Rodentia

Substances

  • Macromolecular Substances
  • Dimethylnitrosamine