HEPATOTOXICITY OF ATRAZINE AND ITS DEGRADATION PRODUCTS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Hepatotoxicity of Atrazine and Its Degradation Products Atrazine is one of the herbicides most heavily used in the world. Our research has been focused on studies of hepatotoxicity of atrazine and its degradation products in aquatic environments. Our hypothesis was that atrazine and its degradation products exert hepatotoxicity via a mechanism of enhancing lipid peroxidation. In the funding period from 6/07 to 5/08, we studied atrazine and its five degradation products (i.e. deethylatrazine, deisopropylatrazine, hydroxyatrazine, deisopropylhydroxyatrazine, and didealkylatrazine) to examine their effects on NADPH induced lipid peroxidation in rat liver microsome. Methods: In vitro incubation tests were performed. After incubation, TBAS assay for aldehydic compounds and HPLC-MS/MS assay for 4-hydroxynonenal were carried out to assess the oxidative stress status. Results: The study revealed that hydroxyatrazine enhanced significantly the lipid peroxidation while the other five compounds tested did not exhibit observable effects. Significant damage was caused by hydroxyatrazine as evaluated against atrazine. Computational modeling study was performed to identify potential structure-activity relationships. It seemed that the particular charge distribution in hydroxyatrazine played an important role in enhancing lipid peroxidation. In addition, we developed an effective nanoparticle-based solid phase extraction procedure to extract/enrich these agrichemicals from water samples for subsequent quantitative assay by liquid chromatography coupled to tandem mass spectrometry. This protocol was the first of its kind to the best of our knowledge. It is believed that the protocol will find wide applications in research areas such as environmental health, remediation, and toxicology.