ABSTRACT
Nuclear factor erythroid-related factor 2 (Nrf2) has been implicated in several detoxifying and antioxidant defense processes. Nrf2-mediated heme oxygenase-1 (HO-1) expression was demonstrated to play a key role against oxidative stress. Gastrodin (GSTD) is a well-known active compound isolated from the roots of Rhizoma gastrodiae, a plant used in ancient Chinese traditional medicine. The aim of this work was to investigate whether GSTD could alleviate H2O2-induced oxidative stress in mouse liver sinusoidal endothelial cells (LSECs). In LSECs exposed to 1 mM H2O2, treatment with GSTD (1, 10, or 50 µM) resulted in higher cell viability than the untreated control. Treated cells maintained a higher Bcl2/Bax ratio and suppressed caspase-9 expression compared with untreated cells, reducing cell apoptosis. GSTD was protective for H2O2-induced oxidative injury by reducing the generation of intracellular reactive oxygen species and malondialdehyde. HO-1 and Nrf2 expressions were synergistically upregulated by GSTD. Inhibition of HO-1 by 10 µM zinc protoporphyrin resulted in less protective effects on cell viability and malondialdehyde reduction by GSTD treatment in H2O2-exposed LSECs. Additionally, phosphorylated p38 in LSECs exposed to H2O2 was elevated by GSTD. Inhibition of p38 phosphorylation by SB203580 did not induce Nrf2 and HO-1 expression after 1 or 10 µM GSTD treatment and the protective effect on cell viability and malondialdehyde reduction in H2O2-exposed LSECs was reduced. The data conclusively demonstrated that GSTD-induced HO-1 and Nrf2 expression is involved in protection of LSECs from H2O2-induced oxidative injury, which may be regulated by p38 phosphorylation.
Subject(s)
Benzyl Alcohols/pharmacology , Endothelial Cells/drug effects , Glucosides/pharmacology , Heme Oxygenase-1/metabolism , Hydrogen Peroxide/pharmacology , NF-E2-Related Factor 2/metabolism , Oxidative Stress/drug effects , p38 Mitogen-Activated Protein Kinases/metabolism , Animals , Apoptosis/drug effects , Cell Survival/drug effects , Liver/cytology , Liver/drug effects , Malondialdehyde/metabolism , Mice , Models, Theoretical , Oxidative Stress/physiology , Phosphorylation/drug effects , Reactive Oxygen Species/metabolism , Up-Regulation/drug effects , p38 Mitogen-Activated Protein Kinases/bloodABSTRACT
Personalised health surveillance is infrequent or absent in occupational and environmental medicine. The shortage of functional tests in relevant cells and tissues greatly limits our understanding of environmental exposures and associated disease risk. We evaluated single cell signalling in peripheral blood mononuclear cells from 301 individuals in a cross sectional health survey 18 months after a chemical explosion of sulphorous coker gasoline. The accident created a malodourous environment leading to long-term health complaints. Multiple regression analysis revealed T-cell specific elevated phosphorylation of the stress kinase p-p38 (T180/Y182) among tobacco smokers and monocyte-specific elevated phosphorylation in employees at the explosion site. Other studies of the accident reported reduced tear film stability, and more airway obstruction and subjective health complaints among the employees at the accident site. Elevated monocyte p-p38 in the employee group was independent of such health effects, and could therefore be dependent on the sulphuric malodorous environment. The present study proposes signalling status in leukocytes as a scalable biomarker providing information about environmental exposures.
Subject(s)
Environmental Exposure/analysis , Gasoline/toxicity , Occupational Exposure/analysis , p38 Mitogen-Activated Protein Kinases/blood , Adolescent , Adult , Aged , Environmental Biomarkers/genetics , Female , Humans , Leukocytes, Mononuclear/drug effects , Male , Middle Aged , Norway , Phosphorylation/genetics , Single-Cell Analysis , T-Lymphocytes/drug effects , Young Adult , p38 Mitogen-Activated Protein Kinases/geneticsABSTRACT
OBJECTIVE: To investigate the effect of Antrodia cinnamomea on gene expression related to aortal endothelial injury of rats with hyperlipidemia. METHOD: Fifty SD rats were randomly divided into five groups: the normal control group (NG), the model group (MG), the antrodia cinnamomea groups of low, middle and high doses (AC-LG, AC-MG, AC-HG, 250, 500, 1 000 mg x kg(-1)). The rats were fed with high-fat diets to establish the hyperlipidemia model. After the drug administration for 10 weeks, their serum lipid, SOD, MDA and ox-LDL, LOX-1, P38 MAPK and NF-kappaB mRNA and protein expression were respectively determined, and the aortal endothelial injury was observed under electron microscope. RESULT: In the model group, the contents of TC, TG and LDL-C significant increased (P < 0.01), whereas the content of HDL-C significant decreased (P < 0.01). Compared with the model group, both the AC-M group and the AC-H group showed reduction in endothelial injury and significant decrease in the content of TC, TG and LDL-C (P < 0.05 or P < 0.01). The content of HDL-C increased, but with no significant difference. SOD activity in serum remarkably increased (P < 0.05 or P < 0.01), MDA and ox-LDL levels dramatically decreased (P < 0.05 or P < 0.01). CONCLUSION: A. cinnamomea can alleviate endothelial lipid injury by inhibiting the expressions of LOX-1, P38MAPK and NF-kappaB in aorta and better protect aortal endothelial cells from oxidative lipid injury.