Document Type : Original Article
Authors
1
Pharmaceutical Sciences Research Center, Shiraz University Of Medical Sciences, Shiraz, Iran
2
Henan Key Laboratory of Environmental and Animal Product Safety, College of Animal Science and Technology, Henan University of Science and Technology, Luoyang 471000, Henan, China
3
Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
4
Transplant Research Center, Shiraz University of Medical Sciences
5
Department of Pharmacology-Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
6
Shiraz University of Medical Sciences, Pharmaceutical Sciences Research Center
10.30476/tips.2024.102615.1240
Abstract
Acute pancreatitis (AP) is a severe inflammatory disorder with a significant risk of mortality. However, restricted pharmacological treatments are available against this complication. Carnosine is an endogenous dipeptide with various pharmacological effects, including antioxidative and anti-inflammatory properties. In this study the impact of carnosine in an experimental model of AP is investigated. For this purpose, mice received arginine (two 4 g/kg doses, one-hour intervals, i.p) to induce AP. Then, animals received carnosine (50, 250, and 500 mg/kg, i.p). Serum levels of amylase, lipase, and glucose levels were also significantly increased (P < 0.001). Moreover, alterations in oxidative stress biomarkers in the pancreas, including ROS formation, decreased antioxidant capacity, lipid peroxidation, and glutathione depletion, were detected in the AP group (P < 0.001). A significant increase in the pancreatic level of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) was also evident in the l-arginine-treated mice (P < 0.001). The major pancreatic tissue histopathological changes in the current AP model were the infiltration of inflammatory cells to the pancreas tissue, fluid accumulation, and acinar cell vacuolization/necrosis (P < 0.05). Carnosine significantly reduced serum biomarkers of pancreas injury, alleviated oxidative stress, decreased pro-inflammatory cytokine levels, and improved histopathological changes in the pancreas of mice with AP (P < 0.001). These findings suggest that dipeptide carnosine is a protective agent in pancreatitis, with its antioxidative and anti-inflammatory properties playing a pivotal role in its mechanisms of action. Further research is needed to confirm these protective effects in clinical studies and assess carnosine safety in AP.
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