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ARS Home » Plains Area » Manhattan, Kansas » Center for Grain and Animal Health Research » Grain Quality and Structure Research » Research » Publications at this Location » Publication #392031

Research Project: Grain Composition Traits Related to End-Use Quality and Value of Sorghum

Location: Grain Quality and Structure Research

Title: Pendimethalin induces apoptotic cell death through activating ER stress-mediated mitochondrial dysfunction in human umbilical vein endothelial cells

Author
item LEE, HEE-SEOP - University Of Maryland
item PARK, YEONHWA - University Of Massachusetts
item Smolensky, Dmitriy
item LEE, HO-LEE - University Of Maryland

Submitted to: Food and Chemical Toxicology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/10/2022
Publication Date: 8/17/2022
Citation: Lee, H., Park, Y., Smolensky, D., Lee, H. 2022. Pendimethalin induces apoptotic cell death through activating ER stress-mediated mitochondrial dysfunction in human umbilical vein endothelial cells. Food and Chemical Toxicology. 168:113370. https://doi.org/10.1016/j.fct.2022.113370.
DOI: https://doi.org/10.1016/j.fct.2022.113370

Interpretive Summary: Pendimethalin is an herbicide that is widely used around the world on several crops, including sorghum. This study analyzed the effects of Pendimethalin on blood vessels in a cell culture study. The results indicated that Pendimethalin exhibits toxicity to blood vessel cell and inhibited blood vessel shape formation. Unlike previous reports, this toxicity was not attributed to reactive oxygen species. Further research would be beneficial on the use of this herbicide on crops, including sorghum.

Technical Abstract: Pendimethalin is globally registered for control of a wide range of weeds in agriculture and home landscaping. Human exposure to pendimethalin can occur by the oral route through food and other sources and may contribute to a variety of health problems. Endothelial function is vital to numerous biological processes, and endothelial dysfunction and poor vascular health is associated with increased atherosclerotic events; however, no study has yet investigated the potential adverse effect of pendimethalin on endothelial function and vasculature formation. The objective of the current study is to investigate if pendimethalin may affect the viability and function of vascular endothelial cells. We observed that pendimethalin significantly repressed viability of human endothelial cells, inducing G1 cell cycle arrest and apoptotic/necrotic cell death. Pendimethalin treatment also activated ER stress and autophagy, leading to loss of mitochondrial membrane potential. In addition, pendimethalin impaired the tube forming and migratory abilities of endothelial cells. This study provides new insight regarding the potent adverse effects of pendimethalin in vascular endothelial cells, mediated by ER stress-induced mitochondrial dysfunction.