Pyrroloquinoline quinone attenuates cypermethrin-induced liver fibrosis and modulates GLS1-associated metabolic regulation in mice.

Abstract

The use of cypermethrin, a widely used pyrethroid insecticide, has raised concerns about residues and toxicity, including hepatotoxicity, in non-target mammals. PQQ is a redox-active compound with reported antioxidant and cytoprotective properties in multiple experimental systems. Liver fibrosis, a response to liver injury, involves hepatic stellate cell activation and ECM secretion. This study investigated the effects of PQQ on cypermethrin-induced hepatic fibrosis in mice and the associated signaling and metabolic changes. Western blot analysis showed that CYP exposure was accompanied by increased TGF-β1 expression and p38 MAPK phosphorylation, whereas PQQ treatment was associated with reductions in these changes. Notably, PQQ reduced GLS1 expression, accompanied by decreased expression of the HSC activation markers α-SMA and COL1A1. Pharmacological inhibition of GLS1 and changes in intracellular α-KG further supported the involvement of GLS1-associated metabolic regulation in CYP-induced HSC activation. These findings support the involvement of GLS1-associated metabolic regulation in CYP-induced HSC activation and the effects of PQQ, while the causal relationships among the signaling and metabolic changes remain to be established.