Pendimethalin exposure induces bovine mammary epithelial cell death through excessive ROS production and alterations in the PI3K and MAPK signaling pathways

Herbicides are chemicals that have been established to have adverse impacts. However, they are still widely used in agriculture. Pendimethalin (PDM) is an herbicide that is widely used in many countries to control annual grasses. The possibility of livestock being exposed to PDM is relatively high, considering the half-life of PDM and its residues in water, soil and crops. However, the toxicity of PDM in cattle, especially in the mammary glands, has not been reported. Therefore, we investigated whether PDM has toxic effects in the mammary epithelial cells (MAC-T) of cattle. MAC-T cells were treated with various doses (0, 2.5, 5 and 10 μM) of PDM. We found that PDM affected cell viability and cell proliferation and causes cell cycle arrest. Furthermore, PDM triggered cell apoptosis, induced excessive ROS production and mitochondrial membrane potential (MMP) loss, and disrupted calcium homeostasis. In addition, PDM altered the activation of proteins associated with the endoplasmic reticulum (ER) stress response and modified PI3K and MAPK signaling cascades. In conclusion, our current study unveiled the mechanism of PDM in MAC-T cells and we suggest that PDM might be harmful to the mammary gland system of cattle, possibly affecting milk production.