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Received Oct 12, 2017; Revised Jan 28, 2018; Accepted Feb 5, 2018
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1. Introduction
Acute pancreatitis (AP) is an acute and life-threatening inflammatory disease that commonly damages peripancreatic tissues and other distant organs, leading to nearly 250,000 inpatient admissions at a cost of approximately $2.2 billion in the United States annually [1]. Pathophysiological characteristics of AP include local pancreatic tissue injury, systemic inflammatory responses, and multiorgan dysfunctions. Although most of the patients with AP have a mild course of the disease, 15% to 25% of patients with severe acute pancreatitis (SAP) develop into infected pancreatic necrosis and persistent organ failure [2], contributing mostly to AP mortality [3]. There is limited understanding of how the pancreatic acinar cell injury caused by the initial triggering events progresses into local tissue damage and even systemic inflammation. SAP, due to excessive release of inflammatory factors and increased oxidative stress response, can cause distant organ damage, especially acute lung injury. In addition, there is no effective therapeutic strategy for acute pancreatitis so far. It is well known that AP is a typical acute inflammatory response disease involving a variety of inflammatory cytokines, the activation of inflammasome, and the oxidative stress [4].
Naringenin (Nar) is a type of flavonoid, the predominant flavanone in grapefruit. Nar has been shown to have anti-inflammatory properties, organ-protective effects [5], and antioxidative functions [6]. Nar is involved in the regulation of many metabolic and signal transduction pathways such as the nuclear factor signaling pathway [7]. A recent study indicated that naringenin significantly protected against lipopolysaccharide-induced acute lung injury in rats [8]. Other studies have shown that oxidative stress plays a key role in the pathogenesis of acute pancreatitis induced by caerulein (Cae) [9, 10]. Free radicals have been found to participate in the development of the necrotic types of SAP induced by L-arginine (L-arg) [11]. Hence, in order to investigate the role of Nar in AP and the accompanying organ dysfunctions in mice as well as the underlying mechanisms, we used two animal models, Cae-induced mild acute pancreatitis (MAP) model and L-arg-induced SAP model. Moreover, we...