Exenatide-induced chronic damage of pancreatic tissue in rats.

OBJECTIVE: The study aimed to explore exenatide-induced damage of pancreatic tissue in rats. METHODS: At first stage, 30 male rats were randomly divided into exenatide and control groups. At second stage, 10 male and 10 female rats were treated according to sex, exenatide dose and time, and with or without inhibitor. Exenatide was injected subcutaneously twice a day, and body weights were measured once a week. At approximately 10 weeks, blood and pancreatic tissue samples were harvested. Amylase, lipase, interleukin 1, interleukin 6, and tumor necrosis factor α in serums were determined. Pancreatic tissues were divided for dry-wet ratio, myeloperoxidase, hematoxylin-eosin staining, and electric microscope imaging. RESULTS: Compared with the control group, myeloperoxidase in pancreatic tissue of rats administered with exenatide exhibited a significantly high level; dry-wet ratio of pancreatic tissue in rats administered with exenatide exhibited a significantly low level. Chronic pancreatic damage was observed in 30% of rats from exenatide group for both sexes and showed pycnosis of acinar cells, increased cytoplasmic vacuoles, widened cellular gap, and inflammatory cell infiltration in pancreatic tissue. No pancreatic damage was observed in the control and the inhibitor groups. Histopathological evaluation scores in exenatide group were significantly higher than those of the control group. CONCLUSION: Long-term administration of exenatide in rats can result in chronic pancreatic damage.