%0 Journal Article %A EDIT NADASI %A JEB S. CLARK %A ISTVAN SZANYI %A TIMEA VARJAS %A ISTVAN EMBER %A RADHAKRISHNA BALIGA %A ISTVAN ARANY %T Epigenetic Modifiers Exacerbate Oxidative Stress in Renal Proximal Tubule Cells %D 2009 %J Anticancer Research %P 2295-2299 %V 29 %N 6 %X Background: Increased production of reactive oxygen species (ROS) by anticancer drugs has been described in patients with various malignancies, which might attribute to their nephrotoxicity. Materials and Methods: The effects of two epigenetic modifiers - trichostatin A (TSA) and 5-aza-deoxycytidine (5AZA) - on ROS production and cell injury alone or in combination with mild oxidative stress were studied in mouse renal proximal tubule cells. Results: Both agents increased mitochondrial ROS production and consequent lactate dehydrogenase (LDH) release either alone or in combination with a low dose of H2O2. The antioxidant N-acetyl-cysteine (NAC) abolished LDH release. It was also found that CREB-mediated transcription, vital for survival of proximal tubule cells, is attenuated by these anticancer agents. Conclusion: The ROS-inducing activity of TSAI and 5AZA might explain the in vivo nephrotoxicity of epigenetic modifiers. The mechanisms that are responsible for this injury could involve attenuation of pro-survival signaling and/or activation of death signaling pathway(s) associated with mitochondrial ROS release. %U https://ar.iiarjournals.org/content/anticanres/29/6/2295.full.pdf