Protective effect of dieckol against chemical hypoxia-induced cytotoxicity in primary cultured mouse hepatocytes
| Autor: | Yu Jin Jeon, Ho Jae Han, Soo Hyun Park, Min Young Lee, Woochul Chang, Kyung-Sik Song, Hyoung Seok Kim |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Time Factors Cell Survival Pyridines Health Toxicology and Mutagenesis p38 mitogen-activated protein kinases Pharmacology Biology Toxicology p38 Mitogen-Activated Protein Kinases Mice chemistry.chemical_compound medicine Animals Viability assay Cytotoxicity Cells Cultured Nitrobenzenes Benzofurans chemistry.chemical_classification Mice Inbred ICR Sulfonamides Reactive oxygen species Chemical Health and Safety Dose-Response Relationship Drug Imidazoles Public Health Environmental and Occupational Health Cobalt General Medicine Hypoxia (medical) Cell Hypoxia Dieckol Transplantation Biochemistry chemistry Cyclooxygenase 2 Hepatocytes medicine.symptom Reactive Oxygen Species Intracellular |
| Zdroj: | Drug and Chemical Toxicology. 38:180-187 |
| ISSN: | 1525-6014 0148-0545 |
| DOI: | 10.3109/01480545.2014.928719 |
| Popis: | Hepatic ischemic injury is a major complication arising from liver surgery, transplantation, or other ischemic diseases, and both reactive oxygen species (ROS) and pro-inflammatory mediators play the role of key mediators in hepatic ischemic injury. In this study, we examined the effect of dieckol in chemical hypoxia-induced injury in mouse hepatocytes. Cell viability was significantly decreased after treatment with cobalt chloride (CoCl2), a well-known hypoxia mimetic agent in a time- and dose-dependent manner. Pretreatment with dieckol before exposure to CoCl2 significantly attenuated the CoCl2-induced decrease of cell viability. Additionally, pretreatment with dieckol potentiated the CoCl2-induced decrease of Bcl-2 expression and attenuated the CoCl2-induced increase in the expression of Bax and caspase-3. Treatment with CoCl2 resulted in an increased intracellular ROS generation, which is inhibited by dieckol or N-acetyl cysteine (NAC, a ROS scavenger), and p38 MAPK phosphorylation, which is also blocked by dieckol or NAC. In addition, dieckol and SB203580 (p38 MAPK inhibitor) increased the CoCl2-induced decrease of Bcl-2 expression and decreased the CoCl2-induced increase of Bax and caspase-3 expressions. CoCl2-induced decrease of cell viability was attenuated by pretreatment with dieckol, NAC, and SB203580. Furthermore, dieckol attenuated CoCl2-induced COX-2 expression. Similar to the effect of dieckol, NAC also blocked CoCl2-induced COX-2 expression. Additionally, CoCl2-induced decrease of cell viability was attenuated not only by dieckol and NAC but also by NS-398 (a selective COX-2 inhibitor). In conclusion, dieckol protects primary cultured mouse hepatocytes against CoCl2-induced cell injury through inhibition of ROS-activated p38 MAPK and COX-2 pathway. |
| Databáze: | OpenAIRE |
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