Proliferative responses observed following vancomycin treatment in renal proximal tubule epithelial cells

Abstract

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.