Synthetic Triterpenoid RTA dh404 (CDDO-dhTFEA) Ameliorates Acute Pancreatitis
| Autor: | M. Takasu, Michael J. Stamos, Shiri Li, Kelly Vo, Lourdes Robles, Yuichi Masuda, Nosratola D. Vaziri, Hirohito Ichii, Seyed H. Farzaneh, Chie Takasu |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Lipopolysaccharides Necrosis Endocrinology Diabetes and Metabolism pancreatitis medicine.disease_cause Oral and gastrointestinal Rats Sprague-Dawley chemistry.chemical_compound 0302 clinical medicine Endocrinology Malondialdehyde oxidative stress Ceruletide reactive oxygen species Blotting Catalase Active Transport Up-Regulation medicine.anatomical_structure 030220 oncology & carcinogenesis Acute Disease Amylases Acute pancreatitis Cytokines Drug medicine.symptom Inflammation Mediators Pancreas Western medicine.medical_specialty human acinar cell NF-E2-Related Factor 2 Clinical Sciences Blotting Western Active Transport Cell Nucleus Arginine Nrf2 Article Proinflammatory cytokine Dose-Response Relationship 03 medical and health sciences Internal medicine Internal Medicine medicine Animals Humans Oleanolic Acid Cell Nucleus Gastroenterology & Hepatology Hepatology Dose-Response Relationship Drug business.industry Superoxide Dismutase medicine.disease Rats Oxidative Stress 030104 developmental biology chemistry Pancreatitis inflammation Sprague-Dawley Digestive Diseases business Oxidative stress Spleen |
| Zdroj: | Pancreas, vol 45, iss 5 Robles, L; Vaziri, ND; Li, S; Masuda, Y; Takasu, C; Takasu, M; et al.(2016). Synthetic triterpenoid RTA dh404 (CDDO-dhTFEA) ameliorates acute pancreatitis. Pancreas, 45(5), 720-729. doi: 10.1097/MPA.0000000000000518. UC Irvine: Retrieved from: http://www.escholarship.org/uc/item/3pn2h2z3 |
| ISSN: | 1536-4828 |
| DOI: | 10.1097/MPA.0000000000000518. |
| Popis: | Author(s): Robles, Lourdes; Vaziri, Nosratola D; Li, Shiri; Masuda, Yuichi; Takasu, Chie; Takasu, Mizuki; Vo, Kelly; Farzaneh, Seyed H; Stamos, Michael J; Ichii, Hirohito | Abstract: ObjectivesNuclear factor-erythroid-2-related factor (Nrf2) is a ubiquitous transcriptional factor that regulates expression of cellular antioxidant and detoxifying molecules. This study was undertaken to test the hypothesis that administration of the Nrf2 activator (dh404) may attenuate acute pancreatitis.MethodsRats were treated with dh404 (1 mg/kg) 24 hours before induction of pancreatitis and for 3 days thereafter. Pancreatitis was induced with L-arginine (600 mg/100 g) or cerulein (40 μg/kg). Pancreases were processed for histology and malondialdehyde, whereas serum was analyzed for amylase. Islet extracted human pancreatic tissue from organ donors were used for in vitro studies. The tissues were incubated with dh404 at 0, 250, and 500 nM for 30 minutes, 60 minutes, 12 hours, and 24 hours. Nuclear factor-erythroid-2-related factor nuclear translocation and expression of Nrf2's target genes and inflammatory mediators were determined.ResultsThe dh404-treated rat pancreases demonstrated significantly less infiltration of inflammatory cells, destruction of acinar architecture, perilobar edema, and necrosis. Serum amylase and pancreatic malondialdehyde in the dh404-treated rats were significantly lower. dh404-treated human pancreatic tissue showed a significantly higher expression of antioxidant enzymes, lower expression of inflammatory mediators, and greater viability against oxidative stress.ConclusionAdministration of dh404 attenuates acute pancreatitis by lowering oxidative stress and reducing proinflammatory mediators. |
| Databáze: | OpenAIRE |
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