Comprehensive Stereoselectivity Assessment of Toxicokinetics, Tissue Distribution, Cytotoxicity, and Environmental Fate of Chiral Pesticide Propiconazole.

Propiconazole (PRO) has been widely used in the treatment of fungal infection in fruits, vegetables, cereals, and seeds. In this study, a newly established chiral liquid chromatography tandem mass spectrometry method was applied to the systemic stereoselectivity evaluation of PRO enantiomers, including toxicokinetics, tissue distributions, cytotoxicity, accumulation, and degradation. Our results showed that both trans (+)-2S,4S-PRO and cis (-)-2S,4R-PRO had lower Cmax and AUC0-∞ and higher CLz/F values in plasma and lower accumulation concentrations in the liver, heart, and brain. In cytotoxic assays, cis (-)-2S,4R-PRO exhibited the lowest cytotoxicity in PC12 neuronal, N9 microglia, SH-SY5Y neuroblastoma, and MRC5 lung fibroblast cell lines. Moreover, the Eisenia fetida incubation experiment revealed that the accumulations of both trans (+)-2S,4S-PRO and cis (-)-2S,4R-PRO were higher than those of their antipodes in E. fetida. In summary, our findings first suggested that the application of cis (-)-2S,4R-PRO for agriculture would hugely reduce the environmental risk.

Cerebral iron deficiency may induce depression through downregulation of the hippocampal glucocorticoid-glucocorticoid receptor signaling pathway.

BACKGROUND: Iron is a trace essential element to sustain the normal neurological function of human. Many researches had reported the involvement of iron deficiency (ID) in neural development and cognitive functions. However, the role of ID in pathogenesis of depression and its underlying mechanism are still unclear. METHODS: In this study, we first used chronic unpredicted mild stress (CUMS) and iron deprivation mouse models to clarify the pathogenesis role of cerebral ID in depression. Then the role of hippocampal glucocorticoid (GC)-glucocorticoid receptor (GR) pathway in cerebral ID induced depression were elucidated in iron deprivation mice and iron deficiency anemia patients. RESULTS: Our results revealed that both CUMS and iron deprivation could induce cerebral ID in mice, and combination of iron deprivation and CUMS could accelerate the onset and aggravate the symptoms of depression in mice. In hippocampus, ID led to neuronal injury and neurogenesis decrease, which might be related to downregulation of GC-GR signaling pathway caused GR dysfunction, thereby inhibiting the negative feedback regulation function of hippocampus on hypothalamic-pituitary-adrenal (HPA) axis. Moreover, the overactivity of HPA axis in iron deprivation mice and iron deficiency anemia patients also confirmed GR dysfunction. LIMITATIONS: Iron deprivation led to food and water intake decrease of mice, which may affect the behavioral test. In addition, we mainly evaluated the role of hippocampal ID in depression, and the number of iron deficiency anemia patients was limited. CONCLUSIONS: Our results identified that cerebral iron homeostasis was a key factor for maintaining mental stability.

Systemic Stereoselectivity Study of Fenobucarb: Environmental Behaviors in Greenhouse Vegetables, Fruits, Earthworms, and Soils and Its Cytotoxicity.

Fenobucarb (2-sec-butylphenyl methylcarbamate, BPMC) is a potent carbamate pesticide with high insecticidal activity. In this study, the enantioselective accumulation of BPMC in earthworms (Eisenia foetida) and dissipation in cabbage, Chinese cabbage, strawberry, and soils were investigated. The samples were prepared using the QuEChERS method and analyzed using fast and sensitive chiral high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) analysis. The stereoselective accumulation of BPMC enantiomers revealed that S-(+)-BPMC was preferentially accumulated in earthworms rather than its antipode. However, the dissipation studies showed that S-(+)-BPMC degraded faster than the R-(-)-isomer in cabbage, Chinese cabbage, strawberry, and soils. Furthermore, the cytotoxic effect of BPMC enantiomers toward PC12 and N9 neuronal, A549 lung cancer, and MRC5 lung fibroblast cell lines was evaluated using an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Compared with R-(-)- and rac-isomers, S-(+)-BPMC exhibited lower cytotoxicity in neuronal cells and a weaker proliferating effect on lung cancer and lung fibroblast cells. Altogether, the findings suggest the use of the pure S-(+)-enantiomer in agricultural management rather than the use of the racemate or the R-(-)-isomer, which might reduce the environmental risk.