Apigenin ameliorates di(2-ethylhexyl) phthalate-induced ferroptosis: The activation of glutathione peroxidase 4 and suppression of iron intake.

Di(2-ethylhexyl) phthalate (DEHP) is a widely artificial persistent organic pollutant, the contamination of which infiltrates daily human life from many aspects, imperceptibly causing damage to multiple organs in the body, including the liver. Apigenin (APG) is widely distributed in vegetables and fruits and can relieve or prevent the injuries caused by exogenous chemicals through various pharmacological effects, such as antioxidant effects. To investigate the mechanism of DEHP-induced liver injury and the antagonistic effects of APG, we treated AML12 cells with 1 mM DEHP and/or APG. Ultrastructural morphology analysis indicated that DEHP induced typical ferroptosis-like damage. In addition, we found that DEHP exposure induced ferroptosis by enhancing reactive oxygen species (ROS) levels, disrupting iron homeostasis and lipid peroxidation, and regulating the expression of ferroptosis-related genes. Notably, supplementation with APG significantly inhibited these abnormal changes, and molecular docking further showed evidence of the activating effects of APG ligand on glutathione peroxidase 4 (GPX4). These results demonstrated that the protective effects of APG on DEHP-induced ferroptosis were achieved by activating GPX4 and suppressing intracellular iron accumulation. This information not only adds to DEHP toxicological data but also provides a basis for the practical application of APG.

The antagonistic effect of selenium on lead-induced apoptosis and necroptosis via P38/JNK/ERK pathway in chicken kidney.

Lead (Pb), as a toxic heavy metal pollutant, has been paid much attention. Pb is often discharged into the environment through the soot, wastewater and waste residue in industrial production, which poses a great threat to animal health. Selenium (Se) is a trace element known to antagonize the toxicity caused by heavy metals. However, the interaction between Se and Pb in chicken kidney and its specific biological mechanism are still unclear. So, we constructed chicken models of Pb exposure and Pb, Se co-exposure. Therefore, we used western blot and qRT-PCR to detect the expression of related genes. The results showed that Pb activated the MAPK signaling pathway by up-regulating the expression of MARK pathway genes to induce the expression of pro-apoptotic genes and necroptosis-related genes. Se can regulate the MARK signaling pathway and attenuated the expression of MAPK pathway genes altered by Pb to reduce apoptosis and necroptosis of chicken kidney cells. Our study gives new ideas for the specific mechanism of Pb nephrotoxicity and provides a reference for comparative medicine and clinical medication.

Th1/Th2 imbalance and heat shock protein mediated inflammatory damage triggered by manganese via activating NF-κB pathway in chicken nervous system in vivo and in vitro.

Manganese (Mn) is a ubiquitous heavy metal pollutant in environment, and excess Mn can damage nervous system of humans and animals. However, molecular mechanism of Mn-induced poultry neurotoxicity on inflammatory injury is still not fully clear. Thus, the purpose of the conducted research was to explore molecular mechanism of inflammatory injury caused by Mn in chicken nervous system. Two Mn poisoning models were established in vivo and in vitro. One hundred and eighty chickens were randomly separated into four groups. One control group was raised drinking water and standard diet. Three Mn groups were raised drinking water, and the standard diet supplemented with three different concentrations of MnCl2 ∙ 4H2O. There were 45 birds and 3 replicates in each group. Neurocytes from chicken embryos were cultured in mediums without and with six different concentrations of MnCl2 ∙ 4H2O in vitro. Our experiments showed that excess Mn caused cerebral histomorphological structure alternations and damage, and increased the expressions (P < 0.05) of inflammation-related factor NF-κB, TNF-α, iNOS, COX-2, and PTGEs in vivo and in vitro, meaning that excess Mn caused inflammatory damage and inflammatory response in chicken nervous system. Moreover, there were an upregulated IFN-γ mRNA expression and a downregulated IL-4 mRNA expression (P < 0.05) in bird cerebra and embryonic neurocytes after exposure to Mn, indicating that Mn exposure caused Th1/Th2 imbalance and immunosuppression. Additionally, in our research, the elevation (P < 0.05) of five HSPs (HSP27, HSP40, HSP60, HSP70, and HSP90) was found, suggesting that HSPs participated molecular mechanism of Mn stress. In addition, the inflammatory toxicity of Mn to chicken nervous system was time- and dose-dependent. Taken all together, our findings indicated that Th1/Th2 imbalance and HSPs mediated Mn-caused inflammatory injury via NF-κB pathway in chicken nervous system in vivo and in vitro.