Ren_2025_Ecotoxicol.Environ.Saf_302_118635

Renal excretion is a primary pathway for heavy metal metabolism. In this study, we established an animal model of molybdenum toxicity and found that Mo exposure led to structural and functional damage to the kidneys. Further multi-omics analyses identified a regulatory network involving "Arachidonic acid metabolism," "Steroid hormone biosynthesis," "Folate biosynthesis," and "Retrograde endocannabinoid signaling," which played a crucial role in the mechanism underlying renal heavy metal excretion injury induced by molybdenum exposure. Notably, the prominent upregulation of Epoxide hydrolase 2 was identified as a potential key biomarker. Additionally, Lecithin, Prostaglandin D2 synthase, NADH dehydrogenase [ubiquinone] flavoprotein 3, Testololactone, and Tetrahydrobiopterin were found to play significant roles in the excretion injury mechanism. This study provides new insights into the mechanism of heavy metal excretion loss and offers valuable directions for the prevention and treatment of kidney damage caused by environmental heavy metal exposure. SIGNIFICANCE: We found that the regulatory network composed of "Arachidonic acid metabolism," "Steroid hormone biosynthesis," "Folate biosynthesis," and "Retrograde endocannabinoid signaling" plays a crucial role in the mechanism of renal heavy metal excretion damage caused by molybdenum exposure. This study provides new insights into the mechanism of heavy metal excretion loss and offers valuable directions for the prevention and treatment of kidney damage caused by environmental heavy metal exposure.