Affordable Access

Publisher Website

Mitochondrial superoxide production contributes to vancomycin-induced renal tubular cell apoptosis

Authors
Journal
Free Radical Biology and Medicine
0891-5849
Publisher
Elsevier
Publication Date
Volume
52
Issue
9
Identifiers
DOI: 10.1016/j.freeradbiomed.2012.02.038
Keywords
  • Vancomycin
  • Nephrotoxicity
  • Reactive Oxygen Species
  • Superoxide
  • Mitochondrial Depolarization
  • Apoptosis
  • Free Radicals
Disciplines
  • Medicine
  • Philosophy

Abstract

Abstract Vancomycin chloride (VCM), a glycopeptide antibiotic, is widely used for the therapy of infections caused by methicillin-resistant Staphylococcus aureus. However, nephrotoxicity is a major adverse effect in VCM therapy. In this study, we investigated the cellular mechanisms underlying VCM-induced renal tubular cell injury in cultured LLC-PK1 cells. VCM induced a concentration- and time-dependent cell injury in LLC-PK1 cells. VCM caused increases in the numbers of annexin V-positive/PI-negative cells and TUNEL-positive cells, indicating the involvement of apoptotic cell death in VCM-induced renal cell injury. The VCM-induced apoptosis was accompanied by the activation of caspase-9 and caspase-3/7 and reversed by inhibitors of these caspases. Moreover, VCM caused an increase in intracellular reactive oxygen species production and mitochondrial membrane depolarization, which were reversed by vitamin E. In addition, mitochondrial complex I activity was inhibited by VCM as well as by the complex I inhibitor rotenone, and rotenone mimicked the VCM-induced LLC-PK1 cell injury. These findings suggest that VCM causes apoptotic cell death in LLC-PK1 cells by enhancing mitochondrial superoxide production leading to mitochondrial membrane depolarization followed by the caspase activities. Moreover, mitochondrial complex I may play an important role in superoxide production and renal tubular cell apoptosis induced by VCM.

There are no comments yet on this publication. Be the first to share your thoughts.

Statistics

Seen <100 times
0 Comments

More articles like this

[Influence of diazoxide on mitochondrial apoptosis...

on Zhongguo wei zhong bing ji jiu... April 2010

Role of mitochondrial Bax, caspases, and MAPKs for...

on Molecular and Cellular Biochem... July 2013

mTOR contributes to ER stress and associated apopt...

on American journal of physiology... Feb 01, 2015
More articles like this..