Original articleAssociation between antioxidants and mild acute pancreatitis
Introduction
Acute pancreatitis (AP) is one of the most important acute gastrointestinal disorders throughout much of the world. The incidence of AP ranges from 4.6 to 100/100,000 persons in Europe [1]. Gallstones are the most common cause of AP, and mortality ranges from 3% for patients with interstitial (oedematous) pancreatitis [2] to 15% for patients who develop necrosis [3]. The rate of hospitalisation for AP continues to increase over time [4]. The Atlanta Classification system was developed at a consensus conference in 1992 to establish standard definitions for classification of AP [5], and recently, a completed revision of the Atlanta Classification and definitions was reported by international consensus [6]. This revised classification of AP identifies two types of the disease: interstitial oedematous pancreatitis and necrotising pancreatitis [6]. Disease severity was classified as mild, moderate and severe in this revision [6]. Mild AP, the most common form, has no organ failure or local and systemic complications and usually resolves in the first week. The major pathophysiologic processes in AP are inflammation, oedema and necrosis of pancreatic tissue [7], [8]. AP is initiated by intracellular activation of pancreatic proenzymes and autodigestion of the pancreas. Destruction of the pancreatic parenchyma first induces inflammatory mediators and early organ failure. Concomitantly, anti-inflammatory cytokines and specific cytokine inhibitors are produced [9]. Over the past 150 years, many animal models of pancreatitis have been developed that have allowed researchers to study the pathogenesis and pathophysiology of AP [10]. Unfortunately, the mechanisms underlying the pathogenesis of AP remain elusive despite significant advances in the last 25 years, and there is no specific therapy because of the obscure pathogenesis [7], [11]. It has been shown in many inflammatory diseases that oxygen radicals play an important role in the development of inflammation [12]. The similarity of inflammatory tissue damage in inflammatory diseases to that in pancreatitis has led many researchers to study oxidative stress (OS) in AP [12]. Over the last 20 years, there has been increasing awareness regarding the role played by OS in AP [13]. OS occurs when there is an imbalance between generation of reactive oxygen species (ROS) and adequate antioxidant defence systems. OS can cause cell damage either directly or by altering the signalling pathways [14]. It has been demonstrated that oxygen-derived free radicals mediate an important step in the initiation of AP in in vivo models of acute experimental pancreatitis [12], [15]. It is suggested that depletion of ROS, which is an indirect marker of products of lipid peroxidation in the acinar cells, leads to low adenosine triphosphate (ATP) state and favours necrosis, while ROS induction favours apoptosis, thus avoiding severe pancreatic damage, and therefore seems to be protective to the acinar cell. Moreover, OS in the neutrophils leads to inflammation and may contribute to pancreatic injury. Thus, OS appears to play a dual role in pancreatitis [14], [15]. Human serum paraoxonase-1 (PON1) is an ester hydrolase that has both arylesterase (ARE) and paraoxonase (PON) activities. PON1 is a high-density lipoprotein (HDL)-associated enzyme with antioxidant functions and can protect low-density lipoproteins (LDLs) from oxidation induced by either copper ion or the free radical generator azobis (amidinopropane) hydrochloride [16], [17]. Thiol plays a key role in protecting cells from OS and has antioxidant effects [18]. OS in AP is less well defined in human clinical trials.
The aim of this study was to identify the role of total antioxidant status (TAS) and total oxidant status (TOS) in patients with acute pancreatitis and correlate them with Ranson/Balthazar score and C-reactive protein (CRP) levels.
Section snippets
Patients
We performed a cross-sectional trial on patients with AP. The study population consisted of 53 patients with AP admitted to the gastroenterology unit within 24 h after onset of the disease. These patients had mild interstitial oedematous AP and were categorised as the AP group. Patients aged under 18 years with chronic underlying diseases (including cardiovascular disorders, malignancy, asthma, allergic rhinitis, cystic fibrosis, metabolic disease, renal or liver disease or immunodeficiency)
Results
Fifty-three patients with mild AP (AP group) and 55 healthy subjects (control group) were enrolled in the study. Characteristics of the patients and controls are shown in Table 1. There were no significant differences between the AP group and control group with regard to gender and age (p > .05). The mean age of patients in the AP group was 54.0 ± 17.4 years, compared with a mean age of 49.6 ± 13.7 years in the control group. PON activity, ARE activity, thiol and TAS levels were significantly
Discussion
AP, an acute inflammatory condition, is believed to be due to premature and inappropriately activated trypsinogen and other digestive enzymes in the pancreatic acinar cells, resulting in ‘autodigestion’ of the pancreas; however, the pathogenesis is still not well understood [11], [24]. Many animal models have been proposed to study the pathogenesis and pathophysiology of pancreatitis [10]. Unfortunately, the mechanisms underlying the pathogenesis of AP remain unclear. Mitochondrial dysfunction
Conflict of interest
The authors declare that there are no conflicts of interest.
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