Trehalose attenuates experimental L-arginine-induced acute pancreatitis in mice by modulating the expression of autophagy-related markers: Beclin-1, LC3-II, and p62/SQSTM1.

Acute pancreatitis (AP) is one of the most common gastrointestinal emergencies, with a fatality rate reaching 30%. Many studies reported defective autophagy in AP. Trehalose, a disaccharide, has been shown to reduce inflammatory injury by restoring autophagy; however, few studies have examined its ability to enhance autophagy in L-arginine-induced AP. Twenty-four adult male Swiss albino mice were assigned to 3 groups: a control group, an L-arginine group, and an L-arginine + trehalose group (2 g/kg once daily for 12 days). Seventy-two hours after the last treatment, all mice were dissected, and blood samples were collected for pancreatic enzyme assessment. Histological assessment and histopathological scoring for pancreatic tissues were performed. To assess autophagic machinery, an immunohistochemical study using antibodies against LC3-II and P62/SQSTM1 was performed, and mRNA expression of the Beclin-1 and LC3-II genes in pancreatic tissues was assessed. The L-arginine group demonstrated significant increases in serum pancreatic lipase and amylase levels (P < 0.001), distortion of the exocrine acini, inflammatory cell infiltration, areas of necrosis, and many autophagic vacuoles. Immunohistochemical analysis showed a significant increase in the percentage of areas occupied by LC3-II and P62 (P < 0.001) and in the gene expression of Beclin-1 and LC3-II compared with the control group (P < 0.001). Compared to the L-arginine group, the L-arginine + trehalose group revealed a significant reduction in serum pancreatic lipase and amylase levels (P < 0.001), intact exocrine acini, and minimal inflammatory cell infiltration, with a significant reduction in the immunohistochemical area percentages of LC3-II and P62 (P < 0.001), and in Beclin-1 and LC3-II gene expressions (P < 0.001). In conclusion, trehalose therapy significantly mitigates pancreatic injury by restoring effective autophagy.