Effect of Pendimethalin on Viability and Function of Endothelial Cells

OBJECTIVES: Environmental contamination by herbicides has become a global concern in agriculture and food production. Pendimethalin, one such herbicide, may cause toxicological and endocrine side effects in animals and humans. The objective of this study was to investigate adverse effects of pendimethalin exposure on the viability and function of human umbilical vein endothelial cells (HUVECs). METHODS: HUVECs were cultured in basal media supplemented with an endothelial cell growth kit. Cell viability was measured by MTT assay. Apoptosis were measured by flow cytometry. Mitochondrial membrane potential was measured by JC-1 staining. Tube formation was examined using an in vitro angiogenesis assay kit. Migration of endothelial cells was measured by wound healing assays. Changes in protein expression were observed using Western blots. RESULTS: Cell viability was decreased in HUVECs treated with either 50 or 100 µM of pendimethalin. The proportion of apoptotic and necrotic cells was increased by pendimethalin. Pendimethalin treatment increased the protein expression of BiP, p-elF2α, and ATF4 (endoplasmic reticulum stress markers) and conversion of LC3 I to LC3 II (an autophagy marker). Additionally, pendimethalin induced loss of mitochondrial membrane potential and repressed tube formation and migratory ability. CONCLUSIONS: This study provides new insight into the adverse effects of pendimethalin in human vascular endothelial cells. FUNDING SOURCES: Partially supported by a Cooperative Agreement from USDA-ARS to the University of Maryland (S-HL).