Prevention effects of ND-07, a novel drug candidate with a potent antioxidative action and anti-inflammatory action, in animal models of severe acute pancreatitis

European Journal of Pharmacology
Jin Hwan LeeKi-Baik Hahm

Abstract

Oxidative stress and inflammation both play major roles in the development of the acute pancreatitis. Currently, a pancreatic enzyme inhibitor with limited efficacy is only clinically available in a few countries, and antioxidants or non-steroidal anti-inflammatory drugs (NSAIDs) provide only partial tissue protection in acute pancreatitis animal models. Here, we introduce a new drug candidate for treating acute pancreatitis named ND-07 [chemical name: 2-acetoxy-5-(2-4-(trifluoromethyl)-phenethylamino)-benzoic acid] that exhibits both potent antioxidative and anti-inflammatory activities. In an electron spin resonance (ESR) study, ND-07 almost blocked hydroxyl radical generation as low as 0.05 μM and significantly suppressed DNA oxidation and cell death in a lipopolysaccharide (LPS)-stimulated pancreatic cell line. In a cerulein plus LPS-induced acute pancreatitis model, ND-07 pretreatment showed significant tissue protective effects, with reductions of serum amylase and lipase levels and pancreatic wet weights. ND-07 not only diminished the plasma levels of malondialdehyde (MDA) and nitric oxide but also significantly decreased prostaglandin E₂ (PGE₂) and expression of tumor necrotizing factor-alpha (TNF-α) in the pancreatic t...Continue Reading

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Citations

Nov 12, 2013·European Journal of Pharmacology·Mirko MagnoneElena Zocchi
Sep 24, 2015·Biochemical and Biophysical Research Communications·Jun LiZongfang Li
Sep 10, 2015·Cytotechnology·Murat BakırMirkhalil Hosseinigouzdagani
Aug 21, 2013·Free Radical Research·J A ArmstrongD N Criddle
Aug 26, 2018·Journal of Gastroenterology and Hepatology·Li TaoBin Wu
Dec 4, 2014·World Journal of Gastroenterology : WJG·Jong-Min ParkKi Baik Hahm
Sep 21, 2019·European Journal of Pharmacology·Carlos Eduardo S MonteiroPedro Marcos Gomes Soares

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