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首页> 外文期刊>International journal of infectious diseases : >Evaluation of the efficacy of valproic acid and suberoylanilide hydroxamic acid (vorinostat) in enhancing the effects of first-line tuberculosis drugs against intracellular Mycobacterium tuberculosis
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Evaluation of the efficacy of valproic acid and suberoylanilide hydroxamic acid (vorinostat) in enhancing the effects of first-line tuberculosis drugs against intracellular Mycobacterium tuberculosis

机译：评估丙戊酸和异戊酰苯胺异羟肟酸（伏立诺他）增强一线结核药物对细胞内结核分枝杆菌的作用

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Background New tuberculosis (TB) drug treatment regimens are urgently needed. This study evaluated the potential of the histone deacetylase inhibitors (HDIs) valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA) to enhance the effects of first-line anti-TB drugs against intracellular Mycobacterium tuberculosis . Methods M. tuberculosis H37Rv cultures were exposed to VPA or SAHA over 6 days, in the presence or absence of isoniazid (INH) and rifampicin (RIF). The efficacy of VPA and SAHA against intracellular M. tuberculosis with and without INH or RIF was tested by treating infected macrophages. Bactericidal activity was assessed by counting mycobacterial colony-forming units (CFU). Results VPA treatment exhibited superior bactericidal activity to SAHA (2-log CFU reduction), while both HDIs moderately improved the activity of RIF against extracellular M. tuberculosis . The bactericidal effect of VPA against intracellular M. tuberculosis was greater than that of SAHA (1-log CFU reduction) and equalled that of INH (1.5-log CFU reduction). INH/RIF and VPA/SAHA combination treatment inhibited intracellular M. tuberculosis survival in a shorter time span than monotherapy (3 days vs. 6 days). Conclusions VPA and SAHA have adjunctive potential to World Health Organization-recommended TB treatment regimens. Clinical evaluation of the two drugs with regard to reducing the treatment duration and improving treatment outcomes in TB is warranted.
机译：背景技术迫切需要新的结核病（TB）药物治疗方案。这项研究评估了组蛋白脱乙酰基酶抑制剂（HDIs）丙戊酸（VPA）和Suberoylanilide异羟肟酸（SAHA）增强一线抗结核药物对细胞内结核分枝杆菌的作用的潜力。方法在存在或不存在异烟肼（INH）和利福平（RIF）的情况下，将结核分枝杆菌H37Rv培养物暴露于VPA或SAHA超过6天。通过处理感染的巨噬细胞来测试VPA和SAHA对抗有或没有INH或RIF的细胞内结核分枝杆菌的功效。通过计数分枝杆菌菌落形成单位（CFU）来评估杀菌活性。结果VPA处理显示出比SAHA更好的杀菌活性（CFU降低了2个对数），而两种HDI均适度提高了RIF对细胞外结核分枝杆菌的活性。 VPA对细胞内结核分枝杆菌的杀菌作用大于SAHA（1-log CFU降低），与INH相等（1.5-log CFU降低）。与单一疗法相比，INH / RIF和VPA / SAHA联合治疗可在更短的时间内抑制细胞内结核分枝杆菌的存活（3天比6天）。结论VPA和SAHA对世界卫生组织推荐的结核病治疗方案具有辅助潜力。有必要就减少结核病的治疗时间和改善治疗效果对这两种药物进行临床评估。

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