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.

Cadmium induces endoplasmic reticulum stress-mediated apoptosis in pig pancreas via the increase of Th1 cells.

Cadmium (Cd), an environmental pollutant, causes several adverse reactions in animals. High dose of Cd has serious cytotoxicities, including the induction of programmed cell necrosis, autophagy and apoptosis, which has aroused wide public concern. The balance of cytokine network is affected by Th1/Th2 balance which is closely related to immune response and the occurrence, development, treatment and outcome of various diseases. Cd can induce severe apoptosis, but the relationship between Cd induced apoptosis and Th1/Th2 balance has not been clarified. In this study, we established a pig Cd poisoning model, exposing to CdCl2 for 40 days (20 mg Cd/kg diet). Firstly, deviation of Th1/Th2 balance was observed by fluorescence staining, and apoptosis was observed by TUNEL staining. Then, real-time fluorescence quantitative analysis and Western blot were used to detect the expression of related proteins. The results show that Cd can interfere with the balance of Th1/Th2 and shift the balance towards Th1. In addition, through the experiments, we found that Cd exposure can increase the expression of glucose-regulated protein 94 (GRP94) and glucose-regulated protein 78 (GRP78), marker proteins of unfolded protein response (UPR). Cd exposure can increase the expression of pancreatic endoplasmic reticulum kinase (PERK), CCAAT-enhancer-binding protein homologous protein (CHOP), inositol-requiring enzyme 1 (IRE-1), activating transcription factor 6 (ATF-6), cysteinyl aspartate specific proteinase (Caspase12), indicating the three branches (ATF6, PERK and IRE-1) of endoplasmic reticulum stress (ER-stress) were activated. Moreover, we found that the expression of pro-apoptosis genes in the downstream pathway of ER-stress increased. In summary, our results indicated that Cd exposure upregulated the expression of pro-apoptosis related genes and caused apoptosis via the activation of the ER-stress signaling pathways in pancreas cells. And these negative effects were correlated with the equilibrium drift of Th1/Th2, increase in the expression and secretion of Th1 cytokines.