Ciprofloxacin (hydrochloride) is an effective and orally active fluoroquinolone antibiotic with antimicrobial and immunomodulatory activities [1]. Ciprofloxacin is an inhibitor of DNA gyrase and topoisomerase IV, enzymes that are responsible for negative supercoiling of chromosomes and separation of DNA strands, thereby hindering the initiation of bacterial replication [2]. Ciprofloxacin is active against a variety of Gram-positive and Gram-negative bacteria, including Staphylococcus aureus, Listeria monocytogenes, Pseudomonas aeruginosa, Legionella, Neisseria gonorrhoeae, and Helicobacter pylori. Ciprofloxacin can be used for the treatment of various bacterial infections [3].
In vitro, Ciprofloxacin (5-50μg/mL; 0-24h) can inhibit cell proliferation and cause cell cycle arrest at the G2/M phase [4]. Ciprofloxacin (100, 200 and 500μg/ml; 18, 24, 48 and 72h) inhibits DNA synthesis in colon cancer cells (CC-531, HT-29, SW-403) in a time- and dose-dependent manner, activates caspases 3, 8 and 9, upregulates the expression of pro-apoptotic Bax, reduces cell proliferation and induces cell apoptosis [5].
In vivo, Ciprofloxacin (30mg/kg/d; single dose; i.p) significantly reduces bacterial load in the lungs and spleens of the Pneumonic Plague mouse model and increases the survival rate of mice [6]. Ciprofloxacin (100mg/kg/day for 4 weeks; gavage) treatment reduces the expression and activity of lysyl oxidase (LOX) in aortic aneurysm and aortic dissection (AAD) mouse model, increases the levels and activities of matrix metalloproteinases (MMP), and increases the fragmentation of elastic fibers and cell damage, and increases the incidence of aortic dissection and rupture [7].
References:
[1] Fukumoto R, Cary LH, Gorbunov NV, et al. Ciprofloxacin modulates cytokine/chemokine profile in serum, improves bone marrow repopulation, and limits apoptosis and autophagy in ileum after whole body ionizing irradiation combined with skin-wound trauma. PLoS One. 2013;8(3):e58389.
[2] Drlica K, Zhao X. DNA gyrase, topoisomerase IV, and the 4-quinolones. Microbiol Mol Biol Rev. 1997;61(3):377-392.
[3] Nilius, A.M., Shen, L.L., Hensey-Rudloff, D., et al. Antimicrob. Agents Chemother. 47(10), 3260-3269(2003).
[4] Tsai WC, Hsu CC, Tang FT, Wong AM, Chen YC, Pang JH. Ciprofloxacin-mediated cell proliferation inhibition and G2/M cell cycle arrest in rat tendon cells. Arthritis Rheum. 2008;58(6):1657-1663.
[5] Herold C, Ocker M, Ganslmayer M, et al. Ciprofloxacin induces apoptosis and inhibits proliferation of human colorectal carcinoma cells[J]. British journal of cancer, 2002, 86(3): 443-448.
[6] Hamblin KA, Armstrong SJ, Barnes KB, Davies C, Laws T, Blanchard JD, Harding SV, Atkins HS. Inhaled Liposomal Ciprofloxacin Protects against a Lethal Infection in a Murine Model of Pneumonic Plague. Front Microbiol. 2017 Feb 6;8:91.
[7] LeMaire SA, Zhang L, Luo W, et al. Effect of Ciprofloxacin on Susceptibility to Aortic Dissection and Rupture in Mice. JAMA Surg. 2018;153(9):e181804.
Ciprofloxacin (hydrochloride)是一种有效的、具有口服活性的氟喹诺酮类抗生素，具有抗微生物和免疫调节活性 [1]。Ciprofloxacin是DNA回旋酶和拓扑异构酶IV的抑制剂，这些酶负责染色体的负超卷曲和DNA链的分离，从而阻碍细菌复制的启动[2]。Ciprofloxacin对多种革兰氏阳性菌和革兰氏阴性菌都有活性，包括金黄色葡萄球菌、单核细胞增生李斯特菌、铜绿假单胞菌、军团菌、淋病奈瑟菌和幽门螺杆菌。Ciprofloxacin可用于治疗等多种细菌感染 [3]。
在体外，Ciprofloxacin（5-50μg/mL; 0-24h）可抑制细胞增殖，并在 G2/M 期阻滞导致细胞周期 [4]。Ciprofloxacin（100, 200 and 500μg/ml; 18, 24, 48 or 72h）在时间和剂量依赖性上抑制了结肠癌细胞（CC-531, HT-29, SW-403）的DNA合成，激活caspases 3, 8和9，上调促凋亡Bax的表达，减少结肠癌细胞的增殖并诱导细胞凋亡 [5]。
在体内，Ciprofloxacin（30mg/kg/d; single dose; i.p）显著降低了肺鼠疫模型小鼠中肺和脾脏的细菌负荷并提高小鼠存活率 [6]。Ciprofloxacin（100mg/kg/day for 4 weeks; gavage）治疗降低了主动脉瘤和主动脉夹层（AAD）模型小鼠的赖氨酰氧化酶（LOX）的表达和活性，提高了基质金属蛋白酶（MMP）的水平和活性以及增加了弹性纤维的断裂以及细胞损伤，并增加主动脉夹层和破裂的发生率 [7]。