Treatment with cyclosporine attenuates the inflammatory process and severity of bisphosphonate-induced osteonecrosis of the jaws in rats.

IF 4.6 2区医学 Q2 IMMUNOLOGY

Inflammopharmacology Pub Date : 2025-02-24 DOI:10.1007/s10787-025-01673-6

Camila Costa Dias, Caio Ferreira Freire Caetano, Gabriella Alves Julião Costa, Antônio Alexandre Coelho, José Vitor Mota Lemos, Dayrine Silveira de Paula, Juliana Paiva Marques Lima, Paulo Goberlânio de Barros Silva

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引用次数: 0

Abstract

Introduction: Osteonecrosis usually occurs with necrotic bone exposure in the mandible asymptomatically for long periods but can evolve to present pain, fistula, odor, bleeding, and suppuration.

Objective: To evaluate the influence of cyclosporine treatment and its influence on osteonecrosis in a rat model.

Methods: The animals were randomly divided into 05 groups (n = 8/group). The negative control group (SAL), positive control group treated with zoledronic acid (ZA + SAL), and test groups were treated with cyclosporine A (CsA) at 5, 2.5, and 1.25 mg/kg and treated with ZA. The left lower second molars were extracted. The animals were euthanized 1 month after tooth extraction. Digital radiographs, histological slides, and immunoexpression of IL-2, IL-6, TNF-α, PPAR-γ, c-Fos, c-Jun, FoxP3, and INF-γ were analyzed. Western blot assays were performed to investigate the expression of RORyT. In addition, hematological analysis, body mass variation, and femur mechanical tests were performed.

Results: Radiographs showed that in the groups treated with ZA, there was an increase in the radiolucent area suggestive of osteonecrosis, and treatment with cyclosporine did not reduce this parameter (p < 0.001). In the western blot analysis, animals treated with ZA showed increased expression of RORyT (1.887 ± 0.114) compared to the saline group (0.799 ± 0.107), and treatment with the highest dose of cyclosporine (0.652 ± 0.070) reduced this expression (p < 0.001).

Discussion: Studies have observed bone health in animals treated with CsA. Treatment with this immunosuppressant showed a bone-protective effect of CsA, which corroborates our findings.

Conclusion: Treatment with CsA reduced the immunoexpression of pro-inflammatory cytokines such as IL-2 and TNF-α and decreased the expression of RORyT.

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用环孢素治疗可减轻大鼠双膦酸盐引起的颌骨骨坏死的炎症过程和严重程度。

导言：骨坏死通常发生于下颌骨坏死骨暴露，长期无症状，但可发展为疼痛、瘘管、气味、出血和化脓。目的：探讨环孢素对大鼠骨坏死模型的影响及其对骨坏死模型的影响。方法：随机分为05组（n = 8/组）。阴性对照组（SAL）、阳性对照组（ZA + SAL）和试验组分别给予5、2.5、1.25 mg/kg环孢素A （CsA）和ZA处理。拔除左下第二磨牙。拔牙1个月后安乐死。分析数字x线片、组织切片以及IL-2、IL-6、TNF-α、PPAR-γ、c-Fos、c-Jun、FoxP3和INF-γ的免疫表达。Western blot检测RORyT的表达。此外，还进行了血液学分析、体重变化和股骨力学测试。结果：x线片显示，在接受ZA治疗的组中，提示骨坏死的放射透光面积增加，而环孢素治疗并没有减少这一参数(p讨论：研究已经观察到接受CsA治疗的动物骨骼健康。用这种免疫抑制剂治疗显示出CsA的骨保护作用，这证实了我们的发现。结论：CsA治疗可降低IL-2、TNF-α等促炎因子的免疫表达，降低RORyT的表达。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Inflammopharmacology IMMUNOLOGYTOXICOLOGY-TOXICOLOGY

CiteScore

8.00

自引率

3.40%

发文量

200

期刊介绍： Inflammopharmacology is the official publication of the Gastrointestinal Section of the International Union of Basic and Clinical Pharmacology (IUPHAR) and the Hungarian Experimental and Clinical Pharmacology Society (HECPS). Inflammopharmacology publishes papers on all aspects of inflammation and its pharmacological control emphasizing comparisons of (a) different inflammatory states, and (b) the actions, therapeutic efficacy and safety of drugs employed in the treatment of inflammatory conditions. The comparative aspects of the types of inflammatory conditions include gastrointestinal disease (e.g. ulcerative colitis, Crohn''s disease), parasitic diseases, toxicological manifestations of the effects of drugs and environmental agents, arthritic conditions, and inflammatory effects of injury or aging on skeletal muscle. The journal has seven main interest areas: -Drug-Disease Interactions - Conditional Pharmacology - i.e. where the condition (disease or stress state) influences the therapeutic response and side (adverse) effects from anti-inflammatory drugs. Mechanisms of drug-disease and drug disease interactions and the role of different stress states -Rheumatology - particular emphasis on methods of measurement of clinical response effects of new agents, adverse effects from anti-rheumatic drugs -Gastroenterology - with particular emphasis on animal and human models, mechanisms of mucosal inflammation and ulceration and effects of novel and established anti-ulcer, anti-inflammatory agents, or antiparasitic agents -Neuro-Inflammation and Pain - model systems, pharmacology of new analgesic agents and mechanisms of neuro-inflammation and pain -Novel drugs, natural products and nutraceuticals - and their effects on inflammatory processes, especially where there are indications of novel modes action compared with conventional drugs e.g. NSAIDs -Muscle-immune interactions during inflammation [...]