EOHSI

Exit Pathway in the Kidneys
Protects Against Herbicide Toxicity

Weed control is a challenge that farmers confront on a daily basis. Paraquat is an effective weed killer (herbicide), but at high concentrations it can be toxic to the lungs and kidneys. Our study aimed to identify how the body gets rid of paraquat by attaching it to a “transporter protein” through the kidney into urine (the exit pathway). Knowledge of which proteins remove paraquat from the body can aid scientists and clinicians in predicting how individual differences in this pathway may make some people more or less susceptible to the toxic effects of paraquat and other chemicals.

Lead author, Dr. Xia Wen, prepares human kidney cells for paraquat treatment.

Using genetically-engineered mice and human kidney cells, we demonstrated a critical role for the MDR1 transporter protein in removing paraquat from the kidney into urine. We demonstrated that concentrations of paraquat in the kidney, as well as toxicity to cells, were greater when MDR1protein was not working properly.

We used the chemical PSC833 to prevent the MDR1 transporter from working in human kidney cells. When MDR1 was blocked, the concentration of paraquat inside the cells increased.

Next Steps: We are testing whether a person’s genetic code can alter how MDR1 works to protect the kidney against paraquat toxicity.

Dr. Aleksunes is an Associate Professor in the Rutgers University, Ernest Mario School of Pharmacy, Department of Pharmacology and Toxicology, and the Joint Graduate Program in Toxicology. Dr. Aleksunes was recently awarded Mentor of the Year from the American Foundation for Pharmaceutical Education. Dr. Aleksunes is also a member of the Center for Environmental Exposure and Disease (CEED).

Read the published research:
Wen X, Gibson C, Yang I, Buckley B, Goedken M, Richardson J, Aleksunes L (2014) MDR1 Transporter Protects Against Paraquat-Induced Toxicity in Human and Mouse Proximal Tubule Cells. Toxicological Sciences 141(2):475-83. http://www.ncbi.nlm.nih.gov/pubmed/?term=25015657

Funding:
This research was funded in part by the National Institute of Environmental Health Sciences (NIEHS) through the Center for Environmental Exposures and Disease at EOHSI (NIH-NIEHS P30 ES005022) and The National Institutes of Health Institute of Diabetes and Digestive and Kidney Diseases [DK080774, DK093903]; the National Institutes of Environmental Health Sciences [ES020522, ES021800, and ES007148]. Dr. Christopher Gibson was supported by a Pre- doctoral Fellowship from the American Foundation for Pharmaceutical Education.

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