Histological and Immunohistochemical (ANXA1) Analysis of Bisphosphonate (Zoledronate) Effect on Submandibular and Parotid Glands in Neonatal Rats

Background: Zoledronate, a third generation bisphosphonate, is used for the therapy of bone metastases because of multiple myeloma or solid mass and for hyper-calcaemia of maligancy. Zoledronate is chiefly studied in bone but few are known about its effects on the salivary gland, so the aim of this study is to assess the Annexin-A1expressionand to evaluate the histological effect of zolendronate on submandibular and parotid salivary glands tissue in neonatal rats. Material and method: Forty newborn Wistar albino rats of both sexes with average weight (40-60gm) were randomly divided into four groups A, B, C and D (10 rats for each group). A and B were the control groups of 14 and28 days were sacrificed respectively after injection with a single dose (0.1mg/kg) of sterile saline solution I. V. through the tail vein at age of two weeks. C and D were the experimental groups of 14 and 28 days were sacrificed respectively after injection with a single dose (0.1mg/kg) of zoledronic acid solution I. V. through the tail vein at age of two weeks. H& E staining was used forassessment of histological examination of the collected submandibular and parotid gland samples. Then anti-ANXA1 antibody was used for immunohistochemical investigation ofAnnexin-A1 expression. Results: Histologically, there was a relative increment in the secretory granules in the serous cells of the experimental groups over that of the control groups. Immunohistologically, there was a strong positive expression ofANXA1 in the ductal and myoepithelial cells of parotid and submandibular glands with high significant differences between experimental and control groups especially in 28 days after injection. Conclusion: Zolendronate may affect the secretary mechanism of parotid and submandibular glands due to either slowing exocytosis or incrementing the protein synthesis. The positive localization of Annexin-Al in the ductal epithelium of salivary organs may be due to functional exchange of ions and proteins.