Chronic treatment with zoledronic acid alters the expression levels of inflammatory, bone, and apoptotic markers and Toll-like receptors 2 and 4 in rat dental pulp, Publication date: August 2019 Source: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, Volume 128, Issue 2 Author(s): Paulo Goberlânio de Barros Silva, Antonio Ernando Carlos Ferreira, Camila Carvalho de Oliveira, Maria Elisa Quesado Lima Verde, Milena Oliveira Freitas, Fabrício Bitu Sousa, Mário Rogério Lima Mota, Ana Paula Negreiros Nunes Alves Objective The aim of this study was to evaluate the immunostaining of inflammatory, apoptotic, and bone markers, as well as Toll-like-receptors (TLRs) 2 and 4 in the dental pulp in rats treated with zoledronic acid (ZA). Study Design We administered 4 intravascular infusions of saline (control group) or 0.20 mg.kg−1 ZA in Wistar rats (n = 6/group). After 70 days, the 3 rights molars (n = 18/group) were microscopically evaluated (presence of ectasic/dilated blood vessels and inflammatory cells). Immunohistochemistry was performed for tartrate resistant acid phosphatase 5 (TRAP; cell counting), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), TLR2, TLR4, receptor activator of nuclear kappa B ligand (RANKL), osteoprotegerin (OPG), and caspase-3 (scored 0–3 in odontoblast and nonodontoblast dental pulp cells). Mann-Whitney and Fisher's exact tests and Spearman's correlation were used (GraphPad Prism 5.0). Results There was no alteration in ectasic/dilated blood vessels (P = .101) or inflammatory cells (P = .500), but the number of TRAP-positive cells was reduced in the ZA-group (P = .027). In ZA-group odontoblasts, immunostaining for COX-2 (P = .044), TLR4 (P = .003), OPG (P = .035) and caspase-3 (P = .039) increased, and that for RANKL (P = 0.045) decreased. In nonodontoblast dental pulp cells, RANKL immunostaining decreased (P = .009). In the ZA group, the RANKL/OPG ratio decreased in odontoblast (P = .022) and nonodontoblast dental pulp cells (P = .007). IL-6 did not differ between the groups. Conclusions ZA increases the expression levels of inflammatory, apoptotic markers, and TLR4 and alters bone makers in the dental pulp of rats.