title: p-Aminophenol and p-paraphenylenediamine induce injury and apoptosis of human HK-2 proximal tubular epithelial cells.
abstract: BACKGROUND
  There is rapidly accumulating evidence that use of oxidized hair dye causes various forms of nephrotoxic injury. However, the regulation and implication of the nephrotoxic injury resulting from p-aminophenol (PAP) and p-paraphenylenediamine (PPD), the main components of oxidized hair dye, remain unknown.
  
  
  METHODS
  To clarify the effect of PAP and PPD, we analyzed the proliferation, lactate dehydrogenase (LDH) levels, apoptosis and subsequent mRNA levels of caspase-3 in HK-2 cells stimulated with different concentrations of PAP or PPD. Cell proliferation was assessed by MTT assay. The production of LDH was determined by Hitachi 7170 biochemical analyzer. The apoptosis of cell was analyzed using flow cytometry and scanning electron microscopy. The mRNA levels of caspase-3 were quantitatively measured by real-time PCR.
  
  
  RESULTS
  The proliferation of HK-2 cells was significantly inhibited by PAP, PPD and each mixed with hydrogen peroxide (H2O2). The level of apoptosis of HK-2 cells, the mRNA levels of caspase-3 and LDH production by PAP or PPD stimulation was significantly higher than controls or after H2O2. A typical apoptotic morphological change was observed under electron microscopy in response to PAP or PPD.
  
  
  CONCLUSIONS
  It appears that caspase-3 may play a key role in the nephrotoxic injury resulting from PAP, PPD or its oxidized form.
authors.affiliation: Department of Nephrology, Second Xiangya Hospital, Institute of Nephrology, Central South University, Changsha, PR China.
authors.forename: Yi-Hua
authors.initials: YH
authors.lastname: Bai
authors.forename: You-Ming
authors.initials: YM
authors.lastname: Peng
authors.forename: Wen-Qing
authors.initials: WQ
authors.lastname: Yin
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.forename: Fu-You
authors.initials: FY
authors.lastname: Liu
authors.forename: Shao-Bin
authors.initials: SB
authors.lastname: Duan
authors.forename: Ping
authors.initials: P
authors.lastname: Xiao
mesh_terms: D000627:Aminophenols / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D005434:Flow Cytometry; D006202:Hair Dyes / Q000633:toxicity*; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D010655:Phenylenediamines / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D018570:Risk Assessment; D013997:Time Factors
chemical_list: D000627:Aminophenols; D006202:Hair Dyes; D010655:Phenylenediamines; D012333:RNA, Messenger; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; C505407:CASP3 protein, human; D053148:Caspase 3; C026729:4-aminophenol; C029728:4-phenylenediamine