據一項新的研究報告，抗生素可殺滅細菌,，但其長期使用可引起線粒體功能障礙并對健康的哺乳動物細胞施加氧化應激作用,。這些發(fā)現(xiàn)可幫助解釋為什么這些藥物會在許多長期接受治療的患者中引發(fā)問題?？股亻L期以來一直是對抗感染性疾病的標準武器,。隨著在醫(yī)學和農業(yè)中的過度使用抗生素和抗生素抗藥性問題變得日益緊迫，在抗生素辯論中又出現(xiàn)了另外一個因子——它們對健康細胞的影響,。長期使用抗生素一直與各種副作用有關系,，其中包括聽力喪失和腎臟損害。傳統(tǒng)思維認為抗生素通過攻擊諸如細胞壁組裝及蛋白質合成等標靶來殺滅細菌,。然而,，數項最近的研究顯示，抗生素可能會引發(fā)活性氧或ROS的產生,，而ROS可破壞細菌的DNA,。然而，關于抗生素是否會在哺乳動物細胞中誘導ROS的產生仍然存在疑問,。
Sameer Kalghatgi在這里特別觀察了殺菌性或可殺死細菌的抗生素對哺乳動物細胞的影響,。研究人員觀察到，3種不同的殺菌性抗生素（喹諾酮類,、β-內酰胺類,、氨基糖苷類）全都會在實驗室中的人類細胞培養(yǎng)中誘導ROS的產生。這種氧化應激會對健康的DNA,、蛋白質及膜脂質造成傷害,。文章的作者在進行更仔細的觀察時發(fā)現(xiàn)，殺菌性抗生素會擾亂細胞線粒體的電子傳遞鏈,，從而導致ROS的積聚,。給予臨床劑量殺菌性抗生素的小鼠會在其血液和乳腺腺體中出現(xiàn)類似的氧化性損害的跡象。然而,，用強力抗氧化劑N-乙酰半胱氨酸進行治療可逆轉ROS的損害,，而不會降低抗生素的殺菌性能。值得注意的是,，文章的作者發(fā)現(xiàn)四環(huán)素——這是一種限制細菌生長但不會殺滅細菌的抑菌性抗生素——不會在細胞內誘發(fā)ROS的損傷,。這些發(fā)現(xiàn)提示，來自殺菌性抗生素的細胞損傷可通過服用抗氧化劑或通過改用抑菌性抗生素而得到預防,。然而,，未來人們需要進行研究來證實這些藥物在人體內的氧化應激作用。一則相關的《焦點》文章就這些發(fā)現(xiàn)進行了討論,。（生物谷Bioon.com）
生物谷推薦英文摘要：
Sci. Transl. Med. DOI: 10.1126/scitranslmed.3006055
Bactericidal Antibiotics Induce Mitochondrial Dysfunction and Oxidative Damage in Mammalian Cells
Sameer Kalghatgi1,*, Catherine S. Spina1,2,3,*, James C. Costello1, Marc Liesa3, J. Ruben Morones-Ramirez1, Shimyn Slomovic1, Anthony Molina3,4, Orian S. Shirihai3 and James J. Collins1,2,3
Prolonged antibiotic treatment can lead to detrimental side effects in patients, including ototoxicity, nephrotoxicity, and tendinopathy, yet the mechanisms underlying the effects of antibiotics in mammalian systems remain unclear. It has been suggested that bactericidal antibiotics induce the formation of toxic reactive oxygen species (ROS) in bacteria. We show that clinically relevant doses of bactericidal antibiotics—quinolones, aminoglycosides, and β-lactams—cause mitochondrial dysfunction and ROS overproduction in mammalian cells. We demonstrate that these bactericidal antibiotic–induced effects lead to oxidative damage to DNA, proteins, and membrane lipids. Mice treated with bactericidal antibiotics exhibited elevated oxidative stress markers in the blood, oxidative tissue damage, and up-regulated expression of key genes involved in antioxidant defense mechanisms, which points to the potential physiological relevance of these antibiotic effects. The deleterious effects of bactericidal antibiotics were alleviated in cell culture and in mice by the administration of the antioxidant N-acetyl-L-cysteine or prevented by preferential use of bacteriostatic antibiotics. This work highlights the role of antibiotics in the production of oxidative tissue damage in mammalian cells and presents strategies to mitigate or prevent the resulting damage, with the goal of improving the safety of antibiotic treatment in people.
