King D W, Smith M A
School of Public Health, University of Texas-Houston Health Science Center, Houston, TX 77030, USA.
Toxicol In Vitro. 2004 Dec;18(6):797-803. doi: 10.1016/j.tiv.2004.03.013.
Vancomycin (VAN) is a glycopeptide antibiotic used to treat gram-positive infections. Nephrotoxicity is a common side effect observed with vancomycin therapy. However, the mechanism of vancomycin-induced nephrotoxicity has not been fully characterized. In this study we examined the effect of vancomycin on cellular proliferation in renal proximal tubule cells. A dose- and time-dependent increase in cell number and total cellular protein was observed following vancomycin exposure. Vancomycin exposure also caused an increase in BrdU incorporation followed by the accumulation of renal proximal tubule cells in G(2)/M phase of the cell cycle. These effects were inhibited by pretreatment with the mitogen-activated protein kinase inhibitor, PD098059, suggesting an association between the cell proliferative effect of VAN and the induction of the mitogen-activated protein kinase signaling pathway. Mitochondrial function in renal proximal tubule cells was assessed using oxygen consumption and ATP concentrations. We observed an increase in oxygen consumption and ATP concentrations following short-term exposure to vancomycin. Together, our data suggest that vancomycin treatment produces alterations in mitochondrial function that coincide with a cell proliferative response in renal proximal tubule epithelial cells.
万古霉素（VAN）是一种用于治疗革兰氏阳性菌感染的糖肽类抗生素。肾毒性是万古霉素治疗中常见的副作用。然而，万古霉素诱导肾毒性的机制尚未完全明确。在本研究中，我们检测了万古霉素对肾近端小管细胞增殖的影响。万古霉素暴露后，观察到细胞数量和总细胞蛋白呈剂量和时间依赖性增加。万古霉素暴露还导致5-溴脱氧尿嘧啶核苷（BrdU）掺入增加，随后肾近端小管细胞在细胞周期的G（2）/M期积累。丝裂原活化蛋白激酶抑制剂PD098059预处理可抑制这些效应，提示万古霉素的细胞增殖作用与丝裂原活化蛋白激酶信号通路的激活之间存在关联。使用氧消耗和ATP浓度评估肾近端小管细胞的线粒体功能。我们观察到短期暴露于万古霉素后氧消耗和ATP浓度增加。总之，我们的数据表明，万古霉素治疗会导致线粒体功能改变，这与肾近端小管上皮细胞的细胞增殖反应一致。
