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

Reactive oxygen species (ROS) mediated accumulation of DNA oxidative damage is closely correlated with liver diseases. 8-oxoguanine (8-oxoG), a rich DNA oxidation product, playing an important role in liver disease progression. Base excision repair (BER) pathway is responsible for the clearance and mismatch repair of 8-oxoG, including more than 30 proteins such as 8-oxoguanine DNA glycosylase1 (OGG1), MutY homolog (MUTYH), MutT homolog protein 1 (MTH1). The abnormal high level of 8-oxoG and dysregulated expression and function of 8-oxoG repair enzymes facilitate the occurrence and development of liver diseases. Therefore, targeting the 8-oxoG production and repair system with agonists or inhibitors may be a promising avenue for the treatment of liver diseases. This review summarized the impact of 8-oxoG accumulation and dysregulated repair enzymes on 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. We also reviewed the natural constituents as potential therapeutic agents regulating 8-oxoG production, repair enzymes and repair system-related signal pathways in oxidative damage-induced liver diseases.