Metformin for Tuberculosis Infection

Bernadette Dian Novita, Ari Christy Mulyono, F. Erwin
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Abstract

Tuberculosis, caused by Mycobacterium tuberculosis (M.tb), remains the biggest infection burden in the word. Rifampin (RIF) and Isoniazid (INH) are the most effective antibiotics for killing M.tb. However, the resistance rate of rifampin and INH are high and lead to almost 35% treatment failure. Metformin enhanced anti tuberculosis efficacy in killing M. tuberculosis through several mechanism, firstly through autophagia mechanism and secondly by activating superoxide dismutase (SOD). Metformin activated mTOR and AMPK then induced more effective autophagy against M.tb. Superoxide Dismutase (SOD) is an enzyme produced in the host’s antioxidant defense system. SOD neutralizes reactive oxygen species (ROS) that excessively produced during phagocytosis process against M.tb. Excessive production of ROS associated with Th1 overactivation and leads into macrophage activity inhibition and excessive tissue damage. Metformin has ability in improving SOD level during inflammation.
二甲双胍治疗肺结核感染
由结核分枝杆菌(M.tb)引起的结核病仍然是世界上最大的感染负担。利福平(RIF)和异烟肼(INH)是杀死结核分枝杆菌最有效的抗生素。然而,利福平和INH的耐药率很高,导致近35%的治疗失败。二甲双胍通过自噬机制和激活超氧化物歧化酶(SOD)增强抗结核作用。二甲双胍激活mTOR和AMPK,诱导更有效的自噬对抗结核分枝杆菌。超氧化物歧化酶(SOD)是在宿主抗氧化防御系统中产生的一种酶。SOD能中和抗结核杆菌吞噬过程中产生的活性氧(ROS)。过量产生ROS与Th1过度激活相关,导致巨噬细胞活性抑制和过度组织损伤。二甲双胍有改善炎症时SOD水平的作用。
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