Effect of CK2 Inhibitor in Caerulein Induced Acute Pancreatitis in a Mouse Model

Abstract

Background: The pathogenesis of caerulein induced acute pancreatitis involves reactive oxygen species, inflammation, and necrosis of the exocrine pancreas. Protein kinase CK2 is formally known as casein kinase2. It is a phosphorylating enzyme of serine/threonine containing proteins. This enzyme plays an important role in the regulation of oxidative stress, inflammation, and apoptosis. While the importance of CK2 in the cancer biology, cell cycle regulation is undisputed, in pancreatic inflammation particularly acute pancreatitis remains elusive. Here, we anticipated the hypothesis to clarify the role of CK2 in acute pancreatitis by using its inhibitor (TBBt, Tetra bromo benzotriazole). Results: In this study, acute pancreatitis in male swiss albino mice was induced by eight hourly intraperitoneal (i.p.) injection of caerulein (50μg/kg/hr). TBBt administered after 60min of last caerulein injection at three different doses (10, 20, and 30 mg/kg/hr, i.p.) for 3 hrs. Dose dependent effect of TBBt was observed against acute pancreatitis. At the dose of 20mg/kg/hr, it has shown protective effect by altering oxidative stress, physical, and biochemical parameters. Furthermore, it altered inflammatory (p-p65 NF-кB, p-Iкβα, COX-2, IL-6, and TNF-α), apoptotic and antiapoptotic mediators (p53, caspase3, PARP, Bcl2, and Sir2), and p47phox subunit of NADPH oxidase. However, when dose shifted to 30mg/kg/hr, it upholds acute pancreatitis by altering above parameters and mediators. Conclusions: These results indicate that at the dose of 20mg/kg/hr, TBBt gives protection against pancreatitis by altering oxidative stress, inflammation, and apoptosis. In contrast, at the dose of 30mg/kg/hr, it aggravates acute pancreatitis by increasing oxidative stress.