據(jù)一項(xiàng)新的研究報(bào)告,，抗生素可殺滅細(xì)菌,，但其長(zhǎng)期使用可引起線粒體功能障礙并對(duì)健康的哺乳動(dòng)物細(xì)胞施加氧化應(yīng)激作用。這些發(fā)現(xiàn)可幫助解釋為什么這些藥物會(huì)在許多長(zhǎng)期接受治療的患者中引發(fā)問(wèn)題,。抗生素長(zhǎng)期以來(lái)一直是對(duì)抗感染性疾病的標(biāo)準(zhǔn)武器,。隨著在醫(yī)學(xué)和農(nóng)業(yè)中的過(guò)度使用抗生素和抗生素抗藥性問(wèn)題變得日益緊迫,，在抗生素辯論中又出現(xiàn)了另外一個(gè)因子——它們對(duì)健康細(xì)胞的影響。長(zhǎng)期使用抗生素一直與各種副作用有關(guān)系,，其中包括聽力喪失和腎臟損害,。傳統(tǒng)思維認(rèn)為抗生素通過(guò)攻擊諸如細(xì)胞壁組裝及蛋白質(zhì)合成等標(biāo)靶來(lái)殺滅細(xì)菌。然而,，數(shù)項(xiàng)最近的研究顯示,，抗生素可能會(huì)引發(fā)活性氧或ROS的產(chǎn)生，而ROS可破壞細(xì)菌的DNA,。然而,，關(guān)于抗生素是否會(huì)在哺乳動(dòng)物細(xì)胞中誘導(dǎo)ROS的產(chǎn)生仍然存在疑問(wèn)。
Sameer Kalghatgi在這里特別觀察了殺菌性或可殺死細(xì)菌的抗生素對(duì)哺乳動(dòng)物細(xì)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(nèi)酰胺類,、氨基糖苷類）全都會(huì)在實(shí)驗(yàn)室中的人類細(xì)胞培養(yǎng)中誘導(dǎo)ROS的產(chǎn)生,。這種氧化應(yīng)激會(huì)對(duì)健康的DNA、蛋白質(zhì)及膜脂質(zhì)造成傷害,。文章的作者在進(jìn)行更仔細(xì)的觀察時(shí)發(fā)現(xiàn),，殺菌性抗生素會(huì)擾亂細(xì)胞線粒體的電子傳遞鏈，從而導(dǎo)致ROS的積聚,。給予臨床劑量殺菌性抗生素的小鼠會(huì)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(qiáng)力抗氧化劑N-乙酰半胱氨酸進(jìn)行治療可逆轉(zhuǎn)ROS的損害,，而不會(huì)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(xì)菌生長(zhǎng)但不會(huì)殺滅細(xì)菌的抑菌性抗生素——不會(huì)在細(xì)胞內(nèi)誘發(fā)ROS的損傷,。這些發(fā)現(xiàn)提示,，來(lái)自殺菌性抗生素的細(xì)胞損傷可通過(guò)服用抗氧化劑或通過(guò)改用抑菌性抗生素而得到預(yù)防,。然而，未來(lái)人們需要進(jìn)行研究來(lái)證實(shí)這些藥物在人體內(nèi)的氧化應(yīng)激作用,。一則相關(guān)的《焦點(diǎn)》文章就這些發(fā)現(xiàn)進(jìn)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.
