title: Tetramethylpyrazine prevents contrast-induced nephropathy by inhibiting p38 MAPK and FoxO1 signaling pathways.
abstract: BACKGROUND
  Apoptosis is recognized as an important mechanism in contrast-induced nephropathy (CIN). As tetramethylpyrazine (TMP) has been recently found to be renoprotective and anti-apoptotic in multiple kidney injuries, we hypothesized that TMP would prevent CIN.
  
  
  METHODS
  An experimental model of CIN was established in rats. Serum creatinine, blood urea nitrogen, plasma cystatin C, urinary N-acetyl-β-glucosaminidase, and urinary γ-glutamyl transpeptidase were measured to evaluate kidney function. Apoptosis was assessed by transmission electron microscopy, transferase-mediated deoxyuridine triphosphate nick end-labeling staining, and poly-ADP-ribose polymerase cleavage. Fork-head box O1 transcriptional factor (FoxO1) mRNA expression was evaluated by quantitative real-time PCR. Phospho-p38 mitogen-activated protein kinase (MAPK) protein expression was assessed by immunohistochemistry and Western blotting.
  
  
  RESULTS
  TMP significantly attenuated the resulting renal dysfunction and renal tubular cell apo-ptosis. Mechanistically, TMP decreased the expression of phospho-p38 MAPK protein and attenuated the increased FoxO1 mRNA and nuclear protein expression. In addition, TMP inhibited inducible nitric oxide synthase and Bax protein expression while it upregulated Bcl-2.
  
  
  CONCLUSIONS
  In summary, this study demonstrated the protective role of TMP against CIN and indicated the effects of TMP may be mediated by the inhibition of p38 MAPK and FoxO1 pathways. Thus, TMP may be a new potential therapeutic agent to prevent CIN.
authors: Division of Nephrolog, Shanghai Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China. shnanshan@hotmail.com
authors: Xuezhong
authors: X
authors: Gong
authors: Qian
authors: Q
authors: Wang
authors: Xiaochun
authors: X
authors: Tang
authors: Yuerong
authors: Y
authors: Wang
authors: Dan
authors: D
authors: Fu
authors: Huayi
authors: H
authors: Lu
authors: Guohua
authors: G
authors: Wang
authors: Svante
authors: S
authors: Norgren
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000517:prevention & control; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D003287:Contrast Media / Q000009:adverse effects*; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D007673:Kidney Cortex Necrosis / Q000139:chemically induced / Q000517:prevention & control; D008297:Male; D046529:Microscopy, Electron, Transmission; D009419:Nerve Tissue Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D011719:Pyrazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects* / Q000378:metabolism; D000071161:Forkhead Box Protein O1
chemical_list: D003287:Contrast Media; D051858:Forkhead Transcription Factors; D009419:Nerve Tissue Proteins; D011719:Pyrazines; D048051:p38 Mitogen-Activated Protein Kinases; C074639:Foxo1 protein, rat; D000071161:Forkhead Box Protein O1; C017953:tetramethylpyrazine