Research of fenvalerate induced neurodevelopmental toxicity by interfering with the action of estrogen / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the estrogen interference property of fenvalerate in neurodevelopmental toxicity.</p><p><b>METHODS</b>Thirty 4-week-old healthy female ICR mice were randomly divided into 6 groups: sham operation group, ovariectomized control group, ovariectomized with estrogen (10 µg/g) group, ovariectomized with fenvalerate (5 µg/g) group, sham operation with fenvalerate group, and ovariectomized with estrogen and fenvalerate group, with 5 mice in each group. Fenvalerate was injected intraperitoneally once a day for 7 consecutive days. Mice were sacrificed at 24 h after the last exposure to separate the hippocampus. Immunofluorescence was used to detect neuron marker (NeuN) and astrocyte marker (GFAP) in hippocampal CA1, CA3, and DG regions.</p><p><b>RESULTS</b>Compared with the sham operation group (numbers of NeuN-positive cells: CA1 (54.00±1.73), CA3 (59.00 ± 1.73), DG (100.00 ± 4.58)), the sham operation with fenvalerate group (CA1 (37.67 ± 2.08), CA3 (41.33 ± 1.15), DG (80.67±0.58)) and ovariectomized control group (CA1 (44.00 ± 3.00), CA3 (51.00 ± 3.00), DG (83.00 ± 1.72)) showed significant decreases in number of neurons (NeuN-positive cells) in the hippocampus (P < 0.05). Compared with the ovariectomized control group, the ovariectomized with fenvalerate group (CA1 (47.67 ± 3.21), CA3 (49.00 ± 1.73), DG (87.33 ± 4.04)) showed no significant change in number of hippocampal NeuN-positive cells. Compared with the ovariectomized with fenvalerate group (CA1 (47.67 ± 3.21), DG (87.33 ± 4.04)), the sham operation with fenvalerate group and ovariectomized with estrogen and fenvalerate group (CA1 (40.00 ± 1.00), DG (78.67 ± 2.31)) experienced significant decreases in NeuN-positive cells (P < 0.05). Compared with the sham operation group (CA3 (11.00 ± 1.12), DG (10.67 ± 1.15)), the sham operation with fenvalerate group (CA3 (18.67 ± 2.07), DG (16.33 ± 1.53)) showed significant increase in number of astrocytes (GFAP-positive) cells (P < 0.05). Compared with the sham operation with fenvalerate group, the ovariectomized with fenvalerate group (CA3 (12.00 ± 1.00), DG (11.68 ± 1.16)) showed significant decrease in GFAP-positive cells (P < 0.05). Compared with the ovariectomized with fenvalerate group, the sham operation with fenvalerate group and ovariectomized with estrogen and fenvalerate group (CA3 (16.67 ± 2.13), DG (15.38 ± 1.42)) showed significant increases in GFAP-positive cells (P < 0.05).</p><p><b>CONCLUSION</b>The interference with circulating estrogen is an important mechanism underlying the neurodevelopmental toxicity of fenvalerate.</p>

Identification of the metabolites of Sinisan extract in rat plasma, urine, feces and bile after intragastric administration / 药学学报

Sinisan is a widely used traditional Chinese medicine (TCM) in treating various diseases; however, the in vivo metabolic profile of its multiple components remains unknown. In this paper, ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was applied to identify the metabolites of Sinisan extract in rat plasma, urine, feces and bile after intragastric administration. Using MS(E) and mass defect filter techniques, 41 metabolites of 10 parent compounds (naringin, naringenin, hesperidin, neohesperidin, liquiritin, liquiritigenin, glycyrrhizic acid, glycyrrhetinic acid, saikosaponin a and saikosaponin d) were detected and tentatively identified. It was shown by our results that these compounds was metabolized to the forms of hydroxylation, glucuronidation, sulfation, glucuronidation with sulfation and glucuronidation with hydroxylation in vivo.