Polymyxin B causes DNA damage in HK-2 cells and mice

Abstract

Increasing incidence of multidrug-resistant bacteria presents an imminent risk to global health. Polymyxins are ‘last-resort’ antibiotics against Gram-negative ‘superbugs’; however, nephrotoxicity remains a key impediment in their clinical use. Molecular mechanisms underlying this nephrotoxicity remain poorly defined. Here, we examined the pathways which led to polymyxin B induced cell death in vitro and in vivo. Human proximal tubular cells were treated with polymyxin B (12.5–100 μM) for up to 24 h and showed a significant increase in micronuclei frequency, as well as abnormal mitotic events (over 40% in treated cells, p < 0.05). Time-course studies were performed using a mouse nephrotoxici..