Effects of glycogen synthase kinase-3[beta] inhibition on the development of cerulein-induced acute pancreatitis in mice *


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Abstract

Objective:Glycogen synthase kinase (GSK)-3 is a ubiquitous serine-threonine protein kinase that participates in a multitude of cellular processes and signal transduction pathways. It also plays an important role in the pathophysiology of a number of diseases characterized by an enhanced or unregulated inflammatory response. Here we investigate the effects of GSK-3[beta] inhibition on the development of experimental acute pancreatitis induced by cerulein in mice.Design:Prospective, randomized study.Setting:University-based research laboratory.Subjects:One-hundred and sixty anesthetized male CD mice.Interventions:Pancreatitis was induced by intraperitoneal injection of cerulein (hourly ×5, 50 μg/kg). In the treatment group, the potent and selective GSK-3[beta] inhibitor 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8) was administered 1 hr and 6 hrs after the first injection of cerulein (10 mg/kg, intraperitoneally). Sham groups were treated with vehicle (0.1 mL of 0.9% NaCl, intraperitoneally) and TDZD-8. In another set of experiments, mice were monitored for 24 days to determine their mortality rate.

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