[Research progress on the mechanism by which benzene metabolites activate the NLRP3 inflammasome via the AhR-ROS pathway to induce hematotoxicity].

Benzene is a widely used organic solvent, and its toxicity to the hematopoietic system has received extensive attention. Long-term benzene exposure primarily leads to hematological diseases such as aplastic anemia, pancytopenia, and leukemia. Benzene is not a direct ligand for the aryl hydrocarbon receptor (AhR), But its metabolites such as hydroquinone (HQ) and 1, 4-benzoquinone (1, 4-BQ) could activate AhR through ligand-independent mechanisms, thereby initiating downstream intracellular signaling pathways and exerting hematopoietic toxicity. The NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome, as an important intracellular signaling platform, may play a significant role in benzene-induced hematotoxicity. However, whether AhR activation can directly regulate NLRP3 inflammasome activation in the chronic benzene poisoning-induced hematopoietic injury model remains to be experimentally verified. Benzene and its metabolites activate AhR, subsequently inducing reactive oxygen species (ROS) -mediated oxidative stress which activates the NLRP3 inflammasome through multiple signaling pathways, ultimately leading to hematopoietic system damage. This article reviews the progress on the regulatory mechanisms of NLRP3 inflammasome activation via the AhR-ROS pathway in benzene metabolite-induced hematopoietic toxicity, providing a theoretical basis for targeted pharmacotherapy of benzene poisoning-related hematological diseases.