Expression profiling of viologen hebicides in a mouse hepatocyte model

Paraquat and diquat are viologen herbicides used in commercial agriculture and for residential outdoor weed control. They are related structurally, each containing multiple aromatic rings and two quaternary ammonium cations. Paraquat is one of the most widely used herbicides in the world; however, due to recent toxicity studies and its association with Parkinson’s disease, it is now available only to commercially licensed users in the United States. In contrast, diquat has not been associated with Parkinson’s disease and is available for both commercial and residential applications in the United States. In general, the proposed mechanism by which toxicity occurs following exposure to either herbicide is similar. Both are readily converted to free radicals via the superoxide anion radical and react with molecular oxygen to generate additional redox products that promote oxidative stress and potentially cell death. Diquat is generally considered a safer alternative to paraquat based on its lower incidence of poisoning reports; however, recent work in our lab suggests diquat is significantly more hepatotoxic than paraquat. Studies reporting direct comparisons of paraquat and diquat, especially regarding their potential impact on liver injury, are definitely lacking. The goal of this project is to address this knowledge gap by exposing an in vitro hepatocellular model (TGF-alpha transgenic mouse hepatocytes; TAMH) with each viologen herbicide to further elucidate toxicologic mechanisms and outcomes. The microarray data identified MAPK as an important contributor to diquat-induced toxicity and offers a new generalized approach for broader gene expression-level investigations.

9