The role of 8-OxoG and its repair systems in liver diseases progression: responsible mechanisms and promising natural products

Chin J Nat Med. 2025 Jul;23(7):815-823. doi: 10.1016/S1875-5364(25)60848-X.

Abstract

The accumulation of deoxyribonucleic acid (DNA) oxidative damage mediated by reactive oxygen species (ROS) is closely associated with liver diseases. 8-Oxoguanine (8-OxoG), a prevalent DNA oxidation product, plays a significant role in liver disease progression. The base excision repair (BER) pathway, comprising over 30 proteins including 8-OxoG DNA glycosylase1 (OGG1), MutY homolog (MUTYH), and MutT homolog protein 1 (MTH1), is responsible for the clearance and mismatch repair of 8-OxoG. Abnormally high levels of 8-OxoG and dysregulated expression and function of 8-OxoG repair enzymes contribute to the onset and development of liver diseases. Consequently, targeting the 8-OxoG production and repair system with agonists or inhibitors may offer a promising approach to liver disease treatment. This review summarizes the impact of 8-OxoG accumulation and dysregulated repair enzymes on various liver diseases, including viral liver disease, alcoholic liver disease (ALD), metabolic dysfunction-associated steatotic liver disease (MASLD), cholestatic liver disease (CLD), liver fibrosis, cirrhosis, and liver cancer. Additionally, we review natural constituents as potential therapeutic agents that regulate 8-OxoG production, repair enzymes, and repair system-related signal pathways in oxidative damage-induced liver diseases.

Keywords: 8-OxoG; Liver disease; Natural medicine; Oxidative stress; Repair mechanism.

Publication types

  • Review

MeSH terms

  • Animals
  • Biological Products* / pharmacology
  • DNA Damage
  • DNA Repair* / drug effects
  • Disease Progression
  • Guanine* / analogs & derivatives
  • Guanine* / metabolism
  • Humans
  • Liver Diseases* / drug therapy
  • Liver Diseases* / genetics
  • Liver Diseases* / metabolism
  • Oxidative Stress

Substances

  • Biological Products
  • Guanine
  • 8-hydroxyguanine