@article {NADASI2295, author = {EDIT NADASI and JEB S. CLARK and ISTVAN SZANYI and TIMEA VARJAS and ISTVAN EMBER and RADHAKRISHNA BALIGA and ISTVAN ARANY}, title = {Epigenetic Modifiers Exacerbate Oxidative Stress in Renal Proximal Tubule Cells}, volume = {29}, number = {6}, pages = {2295--2299}, year = {2009}, publisher = {International Institute of Anticancer Research}, abstract = {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.}, issn = {0250-7005}, URL = {https://ar.iiarjournals.org/content/29/6/2295}, eprint = {https://ar.iiarjournals.org/content/29/6/2295.full.pdf}, journal = {Anticancer Research} }