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柚皮素减轻二氧化钛(TiO)诱导的小鼠慢性关节炎:氧化应激、细胞因子和 NFκB 的作用。

Naringenin mitigates titanium dioxide (TiO)-induced chronic arthritis in mice: role of oxidative stress, cytokines, and NFκB.

机构信息

Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Rod. Celso Garcia Cid Km480 PR445, Cx Postal 10.011, Londrina, Paraná, CEP 86057-970, Brazil.

Departamento de Ciências Farmacêuticas, Centro de Ciências de Saúde, Universidade Estadual de Londrina, Londrina, Brazil.

出版信息

Inflamm Res. 2018 Dec;67(11-12):997-1012. doi: 10.1007/s00011-018-1195-y. Epub 2018 Oct 28.

DOI:10.1007/s00011-018-1195-y
PMID:30370484
Abstract

OBJECTIVE

To evaluate the effect and mechanisms of naringenin in TiO-induced chronic arthritis in mice, a model resembling prosthesis and implant inflammation.

TREATMENT

Flavonoids are antioxidant and anti-inflammatory molecules with important anti-inflammatory effect. Mice were daily treated with the flavonoid naringenin (16.7-150 mg/kg, orally) for 30 days starting 24 h after intra-articular knee injection of 3 mg of TiO.

METHODS

TiO-induced arthritis resembles cases of aseptic inflammation induced by prosthesis and/or implants. Mice were stimulated with 3 mg of TiO and after 24 h mice started to be treated with naringenin. The disease phenotype, treatment toxicity, histopathological damage, oxidative stress, cytokine expression and NFκB were evaluated after 30 days of treatment.

RESULTS

Naringenin inhibited TiO-induced mechanical hyperalgesia (96%), edema (77%) and leukocyte recruitment (74%) without inducing toxicity. Naringenin inhibited histopathological index (HE, 49%), cartilage damage (Toluidine blue tibial staining 49%, and proteoglycan 98%), and bone resorption (TRAP-stained 73%). These effects were accompanied by inhibition of oxidative stress (gp91 93%, NBT 83%, and TBARS 41%) cytokine mRNA expression (IL-33 82%, TNFα 76%, pro-IL-1β 100%, and IL-6 61%), and NFκB activation (100%).

CONCLUSION

Naringenin ameliorates TiO-induced chronic arthritis inducing analgesic and anti-inflammatory responses with improvement in the histopathological index, cartilage damage, and bone resorption.

摘要

目的

评估柚皮素在 TiO 诱导的慢性关节炎中的作用和机制,该模型类似于假体和植入物炎症。

治疗方法

类黄酮是具有重要抗炎作用的抗氧化和抗炎分子。在关节内注射 3mg TiO 后 24 小时,每天用黄酮柚皮素(16.7-150mg/kg,口服)治疗小鼠 30 天。

方法

TiO 诱导的关节炎类似于由假体和/或植入物引起的无菌性炎症病例。用 3mg TiO 刺激小鼠,24 小时后开始用柚皮素治疗小鼠。在治疗 30 天后评估疾病表型、治疗毒性、组织病理学损伤、氧化应激、细胞因子表达和 NFκB。

结果

柚皮素抑制 TiO 诱导的机械性痛觉过敏(96%)、水肿(77%)和白细胞募集(74%),而无毒性。柚皮素抑制组织病理学指数(HE,49%)、软骨损伤(甲苯胺蓝胫骨染色 49%,和糖胺聚糖 98%)和骨吸收(TRAP 染色 73%)。这些作用伴随着氧化应激抑制(gp91 93%,NBT 83%,和 TBARS 41%)细胞因子 mRNA 表达(IL-33 82%,TNFα 76%,pro-IL-1β 100%,和 IL-6 61%)和 NFκB 激活(100%)。

结论

柚皮素改善了 TiO 诱导的慢性关节炎,引起镇痛和抗炎反应,改善了组织病理学指数、软骨损伤和骨吸收。

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