Toxic effect and mechanism of ß-cypermethrin and its chiral isomers on HTR-8/SVneo cells.

Beta-cypermethrin (ß-CYP) consists of four chiral isomers, acting as an environmental estrogen and causing reproductive toxicity, neurotoxicity, and dysfunctions in multiple organ systems. This study investigated the toxic effects of ß-CYP, its isomers, metabolite 3-phenoxybenzoic acid (3-PBA), and 17ß-estradiol (E2) on HTR-8/SVneo cells. We focused on the toxic mechanisms of ß-CYP and its specific isomers. Our results showed that ß-CYP and its isomers inhibit HTR-8/SVneo cell proliferation similarly to E2, with 100 µM 1S-trans-αR displaying significant toxicity after 48 h. Notably, 1S-trans-αR, 1R-trans-αS, and ß-CYP were more potent in inducing apoptosis and cell cycle arrest than 1R-cis-αS and 1S-cis-αR at 48 h. AO/EB staining and flow cytometry indicated dose-dependent apoptosis in HTR-8/SVneo cells, particularly at 100 µM 1R-trans-αS. Scratch assays revealed that ß-CYP and its isomers variably reduced cell migration. Receptor inhibition assays demonstrated that post-ICI 182780 treatment, which inhibits estrogen receptor α (ERα) or estrogen receptor ß (ERß), ß-CYP, its isomers, and E2 reduced HTR-8/SVneo cell viability, whereas milrinone, a phosphodiesterase 3 A (PDE3A) inhibitor, increased viability. Molecular docking studies indicated a higher affinity of ß-CYP, its isomers, and E2 for PDE3A than for ERα or ERß. Consequently, ß-CYP, its isomers, and E2 consistently led to decreased cell viability. Transcriptomics and RT-qPCR analyses showed differential expression in treated cells: up-regulation of Il24 and Ptgs2, and down-regulation of Myo7a and Pdgfrb, suggesting the PI3K-AKT signaling pathway as a potential route for toxicity. This study aims to provide a comprehensive evaluation of the cytotoxicity of chiral pesticides and their mechanisms.

Cytotoxic Effect of the Essential oils from Erigeron Canadensis L. on Human Cervical Cancer HeLa Cells in Vitro.

Erigeron Canadensis L. (E. canadensis) is a widely distributed invasive weed species in China. Potentially anti-cancer qualities may exist in its essential oils (EOs). The purpose of this study was to analyze the components of the EOs of E. canadensis and their effects on the normal liver cell lines L02 and the human cervical cancer cell lines HeLa. The EOs from the upper region of E. canadensis were prepared, its components were identified by GC/MS. Cell viability, cell morphology observation, AO/EB dual fluorescence staining assay, flow cytometry, mitochondrial membrane potential, western blot, caspase inhibitor test, and oxidative stress tests were used to investigate the impact of the EOs on HeLa cells. Network pharmacological analysis was employed to study the potential mechanism of the EOs in the treatment of cervical cancer. According to the findings, the EOs had 21 chemical components, of which limonene made up 65.68 %. After being exposed to the EOs, the cell viability of HeLa and L02 dramatically declined. The inhibition of EOs was more effective than that of limonene when used in an amount equivalent to that in the EOs. L02 cells were less susceptible to the cytotoxicity of EOs than HeLa cells were. Furthermore, EOs altered the cell cycle in HeLa cells and caused oxidative stress and apoptosis. Compared with the control group, the reactive oxygen species (ROS) levels increased in HeLa cells at first and then decreased, total superoxide dismutase (SOD) and catalase (CAT) activities in HeLa cells significantly decreased. G1 phase cells decreased whereas G2/M phase cells increased. The rate of apoptosis rose. Reduced mitochondrial membrane potential and Caspase-3, -9, and -12 protein expression were both observed. Nerolidol, dextroparaffinone, and α-pinene were shown to be the primary components for the suppression of HeLa cells, according to the results of the prediction of pharmacologic targets. In conclusion, findings of this study indicated the EOs may have the potential to curb the growth of cervical cancer cells. Further research is needed to explore the in vivo effect of EOs.

Oral administration of Bacillus cereus GW-01 alleviates the accumulation and detrimental effects of ß-cypermethrin in mice.

Pyrethroid insecticides negatively affect feed conversion, reproductive fitness, and food safety in exposed animals. Although probiotics have previously been widely studied for their effect on gut health, comparatively little is known regarding the efficacy of probiotic administration in specifically reducing pesticide toxicity in mice. We demonstrated that oral administration of a ß-cypermethrin (ß-CY)-degrading bacterial strain (Bacillus cereus GW-01) to ß-CY-exposed mice reduced ß-CY levels in the liver, kidney, brain, blood, lipid, and feces (18%-53%). Additionally, co-administration of strain GW-01 to ß-CY-exposed mice reduced weight loss (22%-31%) and improved liver function (15%-19%) in mice. Additionally, mice receiving GW-01 had near-control levels of numerous ß-CY-affected gut microbial taxa, including Muribaculaceae, Alloprevotella, Bacteroides, Dubosiella, and Alistipes. The survival and ß-CY biosorption of GW-01 in simulated gastrointestinal fluid conditions were significantly higher than E. coli. These results suggested that GW-01 can reduce ß-CY accumulation and alleviate the damage in mice. This study is the first to demonstrate that a probiotic strain can reduce the toxicity of ß-CY in mice.