New insights into Lambda-cyhalothrin-induced lipid metabolism disorder in liver: Crosstalk between oxidative stress and PPARα signaling pathway

Pesticide pollution has become a pressing global environmental concern, primarily driven by the excessive use of pesticides in agricultural practices, resulting in ecosystem degradation and significant risks to human and animal health. Lambda-cyhalothrin (LCT), a widely utilized pyrethroid pesticide, is known to induce multi-organ toxicity, with pronounced effects on the liver. However, the molecular mechanisms underlying LCT-induced hepatotoxicity and effective mitigation strategies remain poorly understood. In this study, we developed in vivo and in vitro LCT exposure models and employed transcriptomics, histopathology, and Molecular Biology techniques to investigate alterations in hepatic lipid metabolism, oxidative stress, Peroxisome Proliferator-activated Receptor alpha (PPARα) signaling, the Cytochrome P450 (CYP450) enzyme system, and the Phosphoinositide 3-kinase (PI3K)/Protein kinase B (Akt) signaling pathway. Furthermore, experiments using oxidative stress inhibitors and PPARα agonists in a hepatocyte cell line (LMH) model demonstrated that LCT modulates CYP450 enzyme system gene expression and suppresses PI3K/Akt pathway activity. Through crosstalk between oxidative stress and PPARα signaling, LCT ultimately disrupts lipid metabolism and induces liver injury. This study provides the first evidence that LCT triggers hepatotoxicity via crosstalk between oxidative stress and PPARα pathways, offering novel insights into optimizing LCT safety guidelines and developing targeted interventions for managing the toxicity of environmental pollutants.

Hepatotoxicity; Lambda-cyhalothrin; Lipid metabolism; Oxidative stress; PPARα signaling pathway.