两种常用氟喹诺酮类抗生素环丙沙星和左氧氟沙星对细胞葡萄糖转运的干扰涉及1型葡萄糖转运蛋白。

Disturbance of cellular glucose transport by two prevalently used fluoroquinolone antibiotics ciprofloxacin and levofloxacin involves glucose transporter type 1.

作者信息

Ge Daniel Tianfang, Law Pui Ying Peggy, Kong Siu-Kai, Ho Yuan-Yuan

机构信息

Department of Biochemistry, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR, China.

出版信息

Toxicol Lett. 2009 Jan 30;184(2):81-4. doi: 10.1016/j.toxlet.2008.10.017. Epub 2008 Oct 28.

DOI:10.1016/j.toxlet.2008.10.017

PMID:19022360

Abstract

Dysglycemia and central nervous system (CNS) complications are the known adverse effects of fluoroquinolone antibiotics. Ciprofloxacin and levofloxacin are among the most prescribed antibiotics. In this study we demonstrate that ciprofloxacin and levofloxacin disturb glucose transport into HepG2 cells and such inhibition is associated with inhibited glucose transporter type 1 (GLUT1) function. When exposed to ciprofloxacin or levofloxacin at maximum plasma concentrations (C(max)) and 5x of C(max) concentrations, GLUT1 mRNA expression, cell surface GLUT1 protein expression and glucose uptake were significantly reduced. These findings imply that disturbed cellular glucose transport and GLUT1 function may underlie the dysglycemic and CNS effects of ciprofloxacin and levofloxacin.

摘要

血糖异常和中枢神经系统（CNS）并发症是氟喹诺酮类抗生素已知的不良反应。环丙沙星和左氧氟沙星是处方量最大的抗生素之一。在本研究中，我们证明环丙沙星和左氧氟沙星会干扰葡萄糖转运进入HepG2细胞，这种抑制作用与1型葡萄糖转运蛋白（GLUT1）功能受抑制有关。当暴露于最大血浆浓度（C(max)）以及5倍C(max)浓度的环丙沙星或左氧氟沙星时，GLUT1 mRNA表达、细胞表面GLUT1蛋白表达和葡萄糖摄取均显著降低。这些发现表明，细胞葡萄糖转运和GLUT1功能紊乱可能是环丙沙星和左氧氟沙星导致血糖异常和中枢神经系统效应的基础。