Zoledronic Acid-Induced Insulitis in Rats

Abstract

Insulitis is the inflammation of beta cells of the Langerhans islets. It is well-known that insulitis is a prevalent complication of diabetes. A series of xenobiotics, including drugs, could also induce insulitis. The current study evaluated the effect of zoledronic acid (ZLD) on the pancreas in an animal model. Actually, in an attempt to evaluate the adverse effects of ZLD on the kidney, we noticed severe morphological alterations in the pancreas. Therefore, the effects of ZLD on the pancreas tissue were further investigated. Rats received ZLD (10 and 15 mg/kg, single dose, i.p) and pancreas weight index, serum biomarkers of pancreas injury, the level of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β), oxidative stress biomarkers in this organ, and pancreas histopathological alterations were assessed. A significant increase in pancreas weight index was detected in ZLD-treated animals. ZLD also significantly increased serum amylase and lipase levels. No significant changes in serum glucose were detected in this study. A significant increase in reactive oxygen species, lipid peroxidation, decreased glutathione levels, and antioxidant capacity was also evident in the pancreas of ZLD-treated rats. Histopathological findings indicate the insulitis lesions of the islets of Langerhans at both doses of 10 and 15 mg/kg of ZLD. The data obtained from this study revealed insulitis as a serious adverse effect associated with high doses of ZLD. Clearly, further studies are warranted to evaluate the effects of other doses and/or patterns of administration of ZLD on pancreas tissue and, finally, the clinical significance of these data.

Keywords

• diabetes
• glucose metabolism
• inflammation
• insulitic lesion
• oxidative stress