Ferroptosis inhibition mitigates glyphosate-induced inflammation and blood-milk barrier disruption in bovine mammary epithelial cells.

Glyphosate (GLY), the primary active component in many herbicides, is widely used in agriculture, and it is associated with impaired mammary gland development. However, the molecular mechanisms underlying its toxicity to mammary epithelial cells remain poorly understood. Ferroptosis, a regulated form of cell death characterized by iron overload and excessive lipid peroxidation, has emerged as a crucial driver of inflammation and barrier dysfunction. In the present study, bovine mammary epithelial cells (MAC-T) were used as an in vitro model to investigate the involvement of ferroptosis in GLY-induced cellular injury. GLY exposure increased intracellular ferrous iron (Fe2+) accumulation, enhanced lipid peroxidation, and elevated reactive oxygen species levels, all of which are hallmarks of ferroptosis. Furthermore, GLY induced inflammatory responses and downregulated tight junction proteins, including ZO-1, Occludin, and Claudin-3, ultimately compromising the integrity of the blood-milk barrier. Notably, treatment with the ferroptosis inhibitor Ferrostatin-1 (Fer-1) attenuated GLY-induced inflammation and barrier disruption significantly. The findings demonstrate that ferroptosis is a key mediator of GLY-induced inflammatory injury and blood-milk barrier dysfunction in mammary epithelial cells, suggesting that ferroptosis is a potential therapeutic target for preventing GLY-associated mammary toxicity.