Azithromycin in combination with riboflavin decreases the severity of Staphylococcus aureus infection induced septic arthritis by modulating the production of free radicals and endogenous cytokines

Azithromycin in combination with riboflavin decreases the severity of Staphylococcus aureus infection induced septic arthritis by modulating the production of free radicals and endogenous cytokines
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DOI:
10.1007/s00011-012-0574-z
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发表时间:
2013-03-01
影响因子:
6.7
通讯作者:
Bishayi, Biswadev
Bishayi, Biswadev
中科院分区:
医学2区
文献类型:
--
作者:
Mal, Pinky;Dutta, Kallol;Bishayi, Biswadev

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确定对抗金黄色葡萄球菌引起的关节炎的替代治疗措施。因此,阿奇霉素与核黄素联合使用,可以对抗体内ROS的产生和炎症。用5×10(6)细菌细胞/只感染小鼠,建立了金黄色葡萄球菌感染性关节炎的体内模型。金黄色葡萄球菌被静脉注射。阿奇霉素和核黄素分别按100 mg/kg体重和20 mg/kg体重单次腹腔注射。分别于感染后第3、9、15天处死小鼠。血清中的肿瘤坏死因子-α、干扰素-γ、白介素6和白介素10,肝、心、肾、脾组织中的超氧化物歧化酶、过氧化氢酶和还原型谷胱甘肽含量降低,在第3天和第9天,CFU在脾和关节中非常显著,在血液中减少。然而,阿奇霉素和核黄素治疗完全根除了血液和脾中的细菌。感染可诱导肿瘤坏死因子-α、干扰素-γ、IL-6和单核细胞趋化蛋白-1的表达,而阿奇霉素和核黄素可下调这些因子的表达。被感染的小鼠也被发现改变了抗氧化状态,以还原型谷胱甘肽和抗氧化酶,如超氧化物歧化酶和过氧化氢酶来衡量。当动物被阿奇霉素和核黄素联合治疗时,这些变化被发现得到改善。
To determine alternate therapeutic measures to combat Staphylococcus aureus induced arthritis. Thus, azithromycin was combined with riboflavin, which may combat the ROS production and inflammation.An in vivo model of S. aureus infection-induced arthritis was set up by infecting mice with 5 x 10(6) bacterial cell/mouse. S. aureus was administered intravenously. Azithromycin and riboflavin was injected intraperitoneally at a single dose of 100 and 20 mg/kg body, respectively. The mice were sacrificed at 3, 9, 15 days post infection (dpi). TNF-alpha, IFN-gamma, IL-6 and IL-10 from serum and SOD, catalase and reduced glutathione concentration were observed in hepatic, cardiac, renal and splenic tissue.CFU was found very prominent in spleen and joints and reduced in blood at 3 and 9 dpi. However, treatment with azithromycin and riboflavin completely eradicated the bacteria from blood and spleen. TNF-alpha, IFN-gamma, IL-6, and MCP-1 were induced due to infection which were downregulated by treatment with azithromycin and riboflavin. Infected mice were also found to have altered antioxidant status, measured in terms of reduced glutathione and anti-oxidant enzymes such as SOD and catalase.These changes were found to be ameliorated when the animals were co-treated with azithromycin and riboflavin.