DOI: 10.1002/ame2.70083
Assessing the therapeutic potential of Tirzepatide in modulating inflammatory responses and mitigating acute pancreatitis
Razan Alawaji
Mohamed S.Abdel-Bakky
Hussein M.Ali
Miad A.Aljuhani
Abdulaziz Arif A.Alshammari
Hashim K.Kamal
Maamoun M.K.Khoja
Kholoud Alsehemi
Mennatallah A.Korani
Eman S.Said
Abstract：Background: Acute pancreatitis (AP) is a severe inflammation of the pancreas, marked by elevated enzyme levels, cellular inflammation, and necrosis. Recent studies emphasize the critical role of inflammation in AP progression. Tirzepatide, a multi-target agonist of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors, has demonstrated notable anti-inflammatory and metabolic benefits.
Methods: This study explores the therapeutic potential of Tirzepatide in pancreatitis induced by L-arginine in rats, focusing on enzymatic markers, cytokine profiles, oxidative stress, and histological outcomes. Over 27 days, rats were distributed into Control, Tirzepatide, L-Arginine, and L-Arginine+Tirzepatide groups, with the latter receiving L-Arginine to induce pancreatitis followed by Tirzepatide administration.
Results: L-Arginine significantly elevated serum amylase, lipase, and inflammatory mediators (IL-6, IL-4, and IL-10), alongside oxidative stress markers and histopathological deterioration. Conversely, the L-Arginine+Tirzepatide group exhibited reduced lipase and IL-6 levels, suppressed reactive oxygen species (ROS) generation, and enhanced anti-inflammatory cytokines IL-4 and IL-10. Histopathological analysis revealed reduced necrosis and tissue damage in the L-Arginine+Tirzepatide group compared to the L-Arginine group, indicating Tirzepatide's possible protective effects. Immunofluorescence studies further demonstrated increased p-Akt expression, supporting the role of Tirzepatide in cellular repair and recovery.
Conclusion: These findings highlight Tirzepatide's ability to mitigate pancreatic damage through antioxidant and anti-inflammatory mechanisms, underscoring its potential as a pharmacological agent for acute pancreatitis.
Keywords：acute pancreatitisdisease treatmentinflammationL-argininep-AktTirzepatide
Publication Date：2025-10-30
Online Publishing Date：2025-12-16(First online date of this platform, not the publication date of the document)
Pages：12( 1876-1887 )