Radiographic and histological evaluation of bisphosphonate alendronate and metotrexate effects on rat mandibles inoculated with Walker 256 carcinosarcoma

Abstract

Radiographic and histological evaluation of bisphosphonate alendronate and metotrexate effects on rat mandibles ABSTRACT Purpose:To investigate the effects of bisphosphosnate alendronate (ALD) and metotrexate (MTX) on an experimental model of Walker 256 carcinosarcoma developed in the oral cavity of rats. Methods: Walker 256 carcinosarcoma cell suspension (0,1 mL) containing 10 6 cell/mL was implanted in the alveoli of the fi rst and second molars. The animals were divided and treated with saline, MTX, ALD, and MTX plus ALD. Later, the animals were sacrifi ced, the tumors were measured and the mandibles were removed for radiographic and histological analysis. Results: In the control group, the radiographic images demonstrated radioluscency with poorly defi ned borders, and the microscopic examination revealed tumor infi ltration into the peripheral and central regions of the bone. Areas of necrosis were commonly seen. In the treated groups with ALD, associated or not with MTX, the radiographic analysis revealed circumscribed tumorinduced osteolysis and various degrees of radiotransparence; while, histologically, preserved bone trabeculae with osteoid formation was observed among malignant cells. Conclusion: The bisphosphonate alendronate exherted an osteoprotective effect and induced bone neoformation on the Walker 256 carcinosarcoma inoculated in rat mandibles. The combination of metotrexate with bisphosphonate alendronate is more successful than treatment with the agents alone in controlling the growth of neoplastic cells and in stimulating reactive new bone. Therefore, this may be an alternative treatment to malignant lesions of maxillaries with osteolysis. Key words: Mouth Neoplasms. Animal Experimentation. Carcinoma 256, Walker. Alendronate. Rats. RESUMO Objetivo:Avaliar o efeito do bisfosfonato alendronato (ALD) e do metotrexato (MTX) em modelo do carcinossarcoma 256 de Walker na mandíbula de ratos. Métodos: Uma suspensão de células tumorais do carcinossarcoma 256 de Walker (0,1mL), na concentração de 10 6 células/mL, foi implantada nos alvéolos de ratos previamente abertos por exodontia. Os animais foram divididos em grupos e tratados com salina, MTX, ALD e associação do MTX com ALD. Após o sacrifício, os tumores foram medidos e as mandíbulas removidas para exames radiográfi co e histológico. Resultados: No exame radiográfi co do grupo controle foi verifi cada área lítica, sem evidência de reparo na região dos alvéolos, e no microscópico, infi ltração óssea periférica e central, de pequenas células tumorais com diversas áreas de necrose. Nos grupos tratados com ALD, associado ou não ao MTX, a análise radiográfi ca mostrou redução da osteólise tumor-induzida com graus variados de radiotransparência na estrutura óssea; enquanto que, na análise histopatológica, trechos de tecido ósseo preservado, com formação de osteóide em meio a células tumorais foram observados. Conclusão: O bisfosfonato alendronato exerceu um efeito osteoprotetor e induziu neoformação óssea em mandíbulas de ratos implantadas com células ...

Effect of different doses of zoledronic acid in establishing of bisphosphonate-related osteonecrosis

“…15,16 After anaesthesia (ketamine 90 mg/kg and xylazine 10 mg/ kg, intraperitoneally), dissection of the first left lower molar was performed with a conventional dental explorer, using a Hollenback 3S extraction spatula and a LeCron Zalle spatula as the-moving lever. [15][16][17][18] All surgical procedures were performed blinded by a single, previously trained operator. From the beginning of the protocol animals were randomly chosen and and stomach (p = 0.0168) in a dose-dependent manner, and the animals treated with ZA showed a lower rate of weight gain (p < 0.0001).…”

“…After decalcification, the material was subjected to histological processes and qualitative analysis by conventional light microscopy. 17 Knowing that ZA can be hepatotoxic 24 and nephrotoxic 25 we performed an analysis of the organs in the experimental protocol. After fixation, the liver, spleen, kidneys and stomach (cardia and fundus regions) were subjected to macroscopic and microscopic analysis based on the presence and extent of lesions in these organs.…”

Facial symmetry evaluation after experimentally displaced condylar process fracture in methotrexate treated rats

“…A series of published studies showed different doses of MTX and administration routes used in experimental models 21,[23][24][25][26][27] . An intraperitoneal administration route was selected since it is frequently used in animals and allows rapid absorption 21,24,25 .…”

“…An intraperitoneal administration route was selected since it is frequently used in animals and allows rapid absorption 21,24,25 .…”

Avaliação da reparação da fratura de côndilo mandibular e da simetria facial em ratos tratados com metotrexato

“…O objetivo deste estudo foi avaliar o reparo ósseo e articular da fratura de côndilo mandibular em ratos que receberam diferentes doses de MTX e não especificamente o tratamento da fratura com este medicamento. Existe uma grande variedade de estudos na literatura com diferentes doses de MTX utilizadas em modelos experimentais com animais (May et al, 1994;Le Bricon et al, 1995;May et al, 1996;Novaes et al, 1996;Vergne et al, 1998;Mello et al, 2000;Fuskevåg et al, 2000;Davies et al, 2002;Laurindo et al, 2003;Silva et al, 2006;Alves et al, 2007;Carvas et al, 2010;Aguiar et al, 2010). A via de administração também é diversa na literatura, sendo a via intraperitoneal utilizada frequentemente (May et al, 1994;Le Bricon et al, 1995;Novaes et al, 1996;Fuskevåg et al, 2000;Laurindo et al, 2003;Silva et al, 2006;Alves et al, 2007;Carvas et al, 2010;Aguiar et al, 2010).…”