Peptidomics in Different Phases of Severe Acute Pancreatitis Model

Severe acute pancreatitis (SAP) involves dynamic shifts from inflammation to immunosuppression, where peptidomic profile evolution may reveal prognostic biomarkers. Here, the plasma peptidome of rats with taurocholate-induced SAP at 1, 3, 6, 12, and 24 h compared with controls was characterized using nLC-MS/MS. Ten peptides derived from eight precursor proteins were differentially regulated across time points. The 12-h period showed eight differentially regulated peptides, while the 6- and 24-h periods had four differentially regulated peptides, and one peptide was regulated between 1 and 3 h. Peptides derived from alpha-1-microglobulin (A1M) increased from 3 h onward, while peptides from actin showed major alterations at 12-24 h, coinciding with peak mortality (46%). Bioinformatic enrichment analyses revealed transient activation of mTOR, JAK/STAT, and cell adhesion pathways at 6 h, followed by bacterial invasion and actin cytoskeleton regulation pathways at later stages. These temporal profiles suggest an early antioxidant response and subsequent structural and infection-related remodeling. These findings suggest that A1M-derived peptides could represent potential early indicators of disease severity, although further validation in human clinical settings is required. These findings highlight the plasma peptidome as a promising tool for clinical diagnostics, providing a better understanding of SAP progression and identification of phase-specific biomarkers in pancreatitis. SUMMARY: This study reveals dynamic changes in the plasma peptidome during the progression of severe acute pancreatitis in rats. Through the identification of differentially regulated peptides, bioinformatic analysis was performed to define the altered pathways and genes, demonstrating the relationship between peptide alterations and disease progression. The 6-h time point after pancreatitis induction showed the highest number of signaling terms/pathways that characterize the inflammatory phase of the disease. In subsequent moments, the enrichment of pathways related to infection and the regulation of the actin cytoskeleton at 12- and 24-h post-pancreatitis induction suggests that this period is associated with the process of bacterial translocation and pancreatic necrosis infection. Therefore, the peptide profile and pathways may have implications for defining prognosis and early diagnosis of infection.