Hepatocyte intracellular signaling pathways regulating oxidative stress and inflammation

Hepatocyte intracellular signaling pathways regulating oxidative stress and inflammation represent a complex network of molecular interactions that maintain liver homeostasis. Central to this network are the Nrf2/KEAP1 pathway, which coordinates the antioxidant response, and the NF-κB and MAPK pathways, which drive inflammatory gene expression in response to cellular stress or injury (Source: PMID: 30634444). In chronic liver diseases like non-alcoholic steatohepatitis (NASH), persistent oxidative stress leads to the activation of these pathways, resulting in hepatocyte apoptosis, recruitment of immune cells, and activation of hepatic stellate cells, which promotes fibrosis (Source: PMID: 28407752). Pharmacological intervention typically targets specific nodes within these pathways, such as activating Nrf2 to enhance detoxification or inhibiting pro-inflammatory kinases to prevent tissue damage (Source: PMID: 31509459). For example, N-acetylcysteine is used to replenish glutathione levels during oxidative insult, while various small molecules are being developed to modulate redox-sensitive transcription factors. However, because these pathways are fundamental to many physiological processes, achieving liver-specific modulation without systemic toxicity remains a significant therapeutic challenge (Source: PMID: 26439520).

Other names

Hepatic redox signalingHepatocyte inflammatory cascadesLiver antioxidant signaling pathwaysHepatic stress response pathways

Modulation of redox-sensitive transcription factors (e.g., Nrf2 activation, NF-κB inhibition) and scavenging of reactive oxygen species to reduce cellular damage and pro-inflammatory cytokine production.