[Aim]

Evaluation of miR-216a-5p and miR-217-5p, known to be pancreas-specific miRNAs, as biomarkers of pancreatic toxicity were performed using L-arginine-induced pancreatitis model in mice.

[Method]

L-arginine HCl was administered intraperitoneally once to male C57BL/6J mice. Necropsy was conducted after 1, 2, 3, 5 and 7 days from administration. Histopathological examination of pancreas, and biomarker measurement including plasma miR-216a-5p and miR-217-5p were performed.

[Result and discussion]

In histopathological examination, pancreatic injury (edema, inflammatory cell infiltration, acinar cell necrosis/degeneration) was observed and their total score was peaked on 3 day of administration. After 5 day of administration, pancreatic injury was decreased, and instead, replacement of inflammatory cells and fibrotic cells appeared. Plasma miR-216a-5p and miR-217-5p was increased corresponding to pancreatic injury and peaked on 3 day after administration. The increase in miRNAs were earlier, greater magnitude, and persisted longer compared with serum amylase or lipase. According to analysis of relation to histopathological score, amylase and lipase didn’t change when acinar cell necrosis/degeneration was relatively weak, while the miRNAs elevated clearly.

In conclusion, miRNAs can identify pancreatic toxicity earlier, and are more sensitive, greater increased and persistent biomarkers than classical biomarkers.