Abstract
Acute pancreatitis (AP) is a multifactorial disease characterized by necroinflammatory changes of the pancreas. Our study is the first study which evaluated the relationship between the free radical production, enzymatic and nonenzymatic antioxidants, oxidative damage, and secretory function of the salivary glands of AP rats. Male Wistar rats were divided equally into 2 groups: control (n = 9) and AP (n = 9). AP was induced by intraperitoneal injection with cerulein and confirmed by higher serum amylase and lipase. We have demonstrated that the superoxide dismutase and glutathione reductase activities, as well as reduced glutathione concentration, were significantly decreased in both the parotid and submandibular glands of AP rats as compared to the control rats. The production of free radicals evidenced as dichlorodihydrofluorescein assay and the activity of NADPH oxidase and xanthine oxidase and IL-1β concentration were significantly higher in the parotid and submandibular glands of AP rats compared to the controls. In AP rats, we also showed a statistical increase in oxidation modification products (advanced glycation end products and advanced oxidation protein products), salivary amylase activity, and significant decrease in the total protein content. However, we did not show apoptosis and any morphological changes in the histological examination of the salivary glands of AP rats. To sum up, cerulein-induced AP intensifies production of oxygen free radicals, impairs the redox balance of the salivary glands, and is responsible for higher oxidative damage to these glands. Interestingly, oxidative modification of proteins and dysfunction of the antioxidant barrier are more pronounced in the submandibular glands of AP rats.
Highlights
Acute pancreatitis (AP) is a multifactorial disease in the course of which digestive enzymes and numerous proinflammatory cytokines are released into the pancreatic interstitium and general circulation, posing a risk of colliquative necrosis of the adjacent tissues and sometimes distant organs
We observed more than 4 times higher increment of CRP concentration in the serum of AP rats compared to the controls (p = 0 001)
In cerulein-induced AP, both the parotid and the submandibular glands are characterized by the normal structure and normal size of the secretory elements (Figure 7). This is the first study to evaluate the effect of cerulein-induced AP on redox balance in the salivary glands
Summary
Acute pancreatitis (AP) is a multifactorial disease in the course of which digestive enzymes and numerous proinflammatory cytokines are released into the pancreatic interstitium and general circulation, posing a risk of colliquative necrosis of the adjacent tissues and sometimes distant organs. The pathogenesis of acute pancreatitis has not been fully explained, one of its factors is believed to be oxidative stress (OS) [2]. It has been demonstrated that nonneutralized ROS are involved in the initiation and can act as a molecular trigger of acute pancreatitis [4]. ROS are the main contributor to cytokine synthesis in pancreatic cells, which occurs through direct activation of the oxidant-sensitive transcription factor, NF-κB, which may disturb the integrity of cytoskeleton and initiate mitochondrial dysfunction in pancreatic cells [4,5,6]. Significantly elevated concentration of plasma lipid peroxidation products, decreased concentration of vitamin C, and correlation between oxidative stress markers and severity of the disease have been demonstrated [8, 9]
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