Abstract

Methoxychlor (MXC), which is an organochlorine pesticide classified as a “Proposed Persistent Organic Pollutant” in the Stockholm Convention. There is ever increasing evidence that organochlorine pesticide exposure can cause damage to the dopamine system and is associated with increased risk of brain disease. However, the specific relationship between MXC and metabolites in the brain is still elusive. Here, we performed mass spectrometry-based metabolomics studies in C57BL/6 mice induced by MXC exposure to further explore its potential pathology mechanism in the brain.

 Female C57BL/6 mice (4 weeks old) were randomly divided into three groups: control, low and high, with at least 6 mice in each group. MXC was administered to the above mice by gavage according to the dosage except the control group. These mice were sacrificed after 4 weeks of treatment, with midbrain and striatum being collected for subsequent metabolomics research. A Q-Exactive mass spectrometer (Thermo Scientific, headquarters), coupled with An Ultimate 3000 UHPLC system was employed for non-targeted metabolomics analysis.
    In our study, metabolites changes in the midbrain and striatum were investigated.  Our results were discussed through pathway analysis included purine pathway, arginine and proline metabolism, glutathione metabolism, phenylalanine, tyrosine and tryptophan biosynthesis etc., which helped to further reveal the possible link between MXC-induced changes in metabolites and brain-related disease.