title: Arsanilic acid causes apoptosis and oxidative stress in rat kidney epithelial cells (NRK-52e cells) by the activation of the caspase-9 and -3 signaling pathway.
abstract: Arsenic exists widely in rock, water and air, and arsanilic acid (also known as aminophenyl arsenic acid) is an organoarsenic compound and has been used as feed additives. Organoarsenic compounds in foodstuff cause adverse effects, including acute and chronic toxicity, in animals and humans. However, little is known about the cellular toxicity and mechanisms of organic arsenic on the kidney. In this study, we explored the toxicity and molecular mechanisms of arsanilic acid on rat kidney epithelial cells (NRK-52e cells). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that arsanilic acid inhibited the proliferation of rat NRK-52e cells in a dose-dependent manner, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay and flow cytometry revealed that arsanilic acid induced cellular apoptosis in NRK-52e cells. Fluorescence spectrophotometer displayed that arsanilic acid caused a loss of mitochondrial transmembrane potential (MMP) of NRK-52e cells, but enhanced reactive oxygen species level of these cells. Notably, trolox, a water-soluble derivative of vitamin E, protected NRK-52e cells against MMP loss and apoptosis caused by arsanilic acid. Western blots with caspase inhibitors further indicated that arsanilic acid increased expression of active caspase-3 and -9 in NRK-52e cells. Collectively, these results suggest that arsanilic acid causes apoptosis and oxidative stress in rat kidney epithelial cells through activation of the caspase-9 and -3 signaling pathway. This study thus provides a novel insight into molecular mechanisms by which arsanilic acid has adverse cytotoxicity on renal tubular epithelial cells.
authors.affiliation: College of Veterinary Medicine, Hunan Agricultural University , 19 East Lake Road, Changsha, Hunan 410128 , China and.
authors.forename: Yin
authors.initials: Y
authors.lastname: Lu
authors.forename: Hui
authors.initials: H
authors.lastname: Yuan
authors.forename: Sijun
authors.initials: S
authors.lastname: Deng
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wei
authors.forename: Chengzhi
authors.initials: C
authors.lastname: Guo
authors.forename: Jine
authors.initials: J
authors.lastname: Yi
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.forename: Rongfang
authors.initials: R
authors.lastname: Li
authors.forename: Lixin
authors.initials: L
authors.lastname: Wen
authors.forename: Zuping
authors.initials: Z
authors.lastname: He
authors.forename: Liyun
authors.initials: L
authors.lastname: Yuan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001147:Arsanilic Acid / Q000633:toxicity*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects*; D004847:Epithelial Cells / Q000378:metabolism*; D007668:Kidney / Q000166:cytology; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013050:Spectrometry, Fluorescence; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; D013844:Thiazoles; D053148:Caspase 3; D053453:Caspase 9; C022616:thiazolyl blue; D001147:Arsanilic Acid