Uso da pentoxifilina e tocoferol na quimionecrose induzida por ácido zoledrônico em mandíbulas de ratos

Abstract

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a painful, debilitating condition, which still has no effective treatment, resulting in mucosal ulceration and bone necrosis, affecting between 0.8 and 12% of the population. This work aims to evaluate the effect of pentoxifylline and tocopherol on BRONJ in the mandible of rats. For this, Wistar rats (180- 200g) were divided into 5 groups: control (C), Zoledronic acid + tooth extraction (AZ+EX), Zoledronic acid + tooth extraction + Pentoxifylline (AZ+EX+P), AZ + EX + Tocopherol (AZ +EX+T) and AZ + EX + Pentoxifylline and Tocopherol (AZ+EX+P+T). Bro was induced through the administration of AZ (0.2 mg / kg, e.v) on days 0, 7, 14 and 49. On the 42nd day, extraction of the lower left first molar (1LLM) was performed. The animals were pre-treated with Pentoxifylline (15 mg / kg / day; i.p) and / or Tocopherol (5.5 mg / kg / day, i.p) up to 2 hours before the 1LLM extraction. The animals were euthanized on day 70. Histopathological analyzes of the mandibles were performed to analyze inflammatory infiltrate, osteoid deposition, apoptotic osteoclasts. Counting of viable osteocytes and empty gaps were performed using the ImageJ software. They were evaluating serum calcium (Ca), phosphorus (P), alkaline phosphatase (FAO), AST, ALT and analysis of oxidative stress in liver and kidney tissues. In the histopathological analysis, the AZ+EX+P+T group improves improvement in bone condition at the tooth extraction site, a greater number of viable osteocytes and a smaller number of empty gaps when compared to the group with BRONJ (p <0.05). The group pretreated with only Tocopherol showed higher levels of FAO and the groups that received higher secondary Pentoxifylline with a serum P level when compared to the BRONJ group (p <0.05). The pre-dissipated blood ALT groups when compared to the BRONJ group (p <0.05). The administration of P + T significantly reduced the levels of hepatic malondialdehyde when compared to the group with BRONJ (p <0.05). Our results suggest that the pre-treatment of P+T improves the bone condition at the site of extraction and does not present systemic toxicity in rats with BRONJ.