ABSTRACT
Accumulation of the heavy metals molybdenum (Mo) and cadmium (Cd) in the liver can induce organelle damage and inflammation, resulting in hepatotoxicity. The effect of Mo and/or Cd on sheep hepatocytes was investigated by determining the relationship between the mitochondria-associated endoplasmic reticulum membrane (MAM) and NLRP3 inflammasome. Sheep hepatocytes were divided into four groups: the control group, Mo group (600 µM Mo), Cd group (4 µM Cd) and Mo + Cd group (600 µM Mo+4 µM Cd). The results showed that Mo and/or Cd exposure increased the levels of lactate dehydrogenase (LDH) and nitric oxide (NO) in the cell culture supernatant, elevated the levels of intracellular Ca2+ and mitochondrial Ca2+, downregulated the expression of MAM-related factors (IP3R, GRP75, VDAC1, PERK, ERO1-α, Mfn1, Mfn2, ERP44), shortened the length of the MAM and reduced the formation of the MAM structure, eventually causing MAM dysfunction. Moreover, the expression levels of NLRP3 inflammasome-related factors (NLRP3, Caspase1, IL-1ß, IL-6, TNF-α) were also dramatically increased after Mo and Cd exposure, triggering NLRP3 inflammasome production. However, an IP3R inhibitor, 2-APB treatment significantly alleviated these changes. Overall, the data indicate that Mo and Cd coexposure leads to structural disruption and dysfunction of MAM, disrupts cellular Ca2+ homeostasis, and increases NLRP3 inflammasome production in sheep hepatocytes. However, the inhibition of IP3R alleviates NLRP3 inflammasome production induced by Mo and Cd.
Subject(s)
Inflammasomes , NLR Family, Pyrin Domain-Containing 3 Protein , Animals , Sheep , Inflammasomes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Cadmium/toxicity , Molybdenum/toxicity , Hepatocytes , Endoplasmic Reticulum/metabolism , MitochondriaABSTRACT
Excessive molybdenum (Mo) and Cadmium (Cd) can adversely affect health status. However, the correlation between mitophagy and mitochondrial dysfunction caused by Mo and Cd and the underlying mechanisms are still unknown. The aim of this study was to investigate the relationship between mitophagy and mitochondrial dysfunction via the ROS-mediated PINK1/Parkin pathway caused by Mo and Cd. Here, Hepa1-6 cells were incubated with (NH4)6Mo7O24.4 H2O (600.0 µM Mo), CdCl2 (10.0 µM Cd), and the combination of reactive oxygen species (ROS) scavenger (N-acetyl-L-cysteine, NAC, 100.0 µM), or mitophagy inhibitor (Cyclosporin A, CsA, 1.0 µM) for 24 h. Results revealed that Mo or/and Cd elevated the level of intracellular ROS and malondialdehyde (MDA) content, reduced superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities. Additionally, Mo or/and Cd could observably increase the percentage of cells with low membrane potential and decrease the content of ATP, elevate the number of autophagosomes and LC3 puncta, upregulate the mRNA and protein levels of LC3II/LC3I, Parkin, Pink1, VDAC1, downregulate mRNA and protein levels of P62. Moreover, treatments with NAC could significantly alleviate the changes of the above factors co-induced by Mo and Cd, and CsA intensify the changes of the above factors. In summary, our results reveal that Mo and Cd co-exposure can cause oxidative stress and mitophagy via the ROS-mediated PINK1/Parkin pathway in Hepa1-6 cells, and inhibition of mitophagy aggravates Mo and Cd co-induced mitochondrial dysfunction.
ABSTRACT
Objective To compare the effect of the domestic infantile type video intubationscope (VIS) and stethoscope in positioning of double-lumen endobronchial tube (DLT). Methods 100 cases of patients underwent elective thoracic surgery requiring single lung ventilation were randomly divided into two groups: domestic infantile type video intubationscope group (group V) and stethoscope group (group S), with 50 cases in each. After intubating with a DLT, the positions of DLT were judged and adjusted by VIS (group V) and stethoscope (group S) respectively, and then reviewed by fiberoptic bronchoscopy (FOB), the positioning time and accuracy were recorded. Results Comparing with the group S, the positioning time of DLT was significantly shorter and the total positioning accuracy of DLT was significantly higher in group V (P < 0.05). Conclusion It is easy and quickly, high accuracy with domestic infantile type video intubationscope in positioning of DLT, which is worthy of clinical popularization and application.
ABSTRACT
Objective To compare the effect of the domestic infantile type video intubationscope (VIS) and stethoscope in positioning of double-lumen endobronchial tube (DLT). Methods 100 cases of patients underwent elective thoracic surgery requiring single lung ventilation were randomly divided into two groups: domestic infantile type video intubationscope group (group V) and stethoscope group (group S), with 50 cases in each. After intubating with a DLT, the positions of DLT were judged and adjusted by VIS (group V) and stethoscope (group S) respectively, and then reviewed by fiberoptic bronchoscopy (FOB), the positioning time and accuracy were recorded. Results Comparing with the group S, the positioning time of DLT was significantly shorter and the total positioning accuracy of DLT was significantly higher in group V (P < 0.05). Conclusion It is easy and quickly, high accuracy with domestic infantile type video intubationscope in positioning of DLT, which is worthy of clinical popularization and application.
