title: Glutathione supplementation to University of Wisconsin solution causes endothelial dysfunction.
abstract: BACKGROUND
  Glutathione (GSH) is added to University of Wisconsin (UW) organ preservation solution to protect against oxidative stress. This study assesses the effect of GSH-supplementation on endothelial function in tissues subjected to cold ischaemia and compares its effects to a mono-ethyl ester equivalent (GSH-MEE) and S-nitrosated GSH (GSNO).
  
  
  METHODS
  Rat aortic rings were stored for 1 h or 48 h in cold, hypoxic UW solution with or without GSH (3 mM), GSH-MEE (3 mM) or GSNO (100 mciroM) supplementation. Aortic rings were reoxygenated in warm Krebs solution; smooth muscle function was assessed by responses to phenylephrine (PE), and endothelial function by vasodilatation to the endothelium-dependent dilator, acetylcholine (ACh). The protective effects against oxidant-induced endothelial cell death were assessed in cultured human umbilical vein endothelial cells (HUVEC).
  
  
  RESULTS
  Supplementation of UW with either GSH or GSH-MEE had no effect on vascular responses to PE, but smooth muscle contraction was significantly attenuated in rings incubated for 48 h with GSNO. Endothelium-dependent relaxation was significantly impaired in tissues stored under hypoxic conditions in GSH, GSH-MEE and GSNO supplemented UW solution for 1 h. However, impairment at 48 h was significantly more pronounced in GSH-treated vessels. Cultured HUVEC death was exacerbated by GSH and GSH-MEE in unstressed cells and in those stressed with a superoxide anion generator.
  
  
  CONCLUSIONS
  GSH supplementation of UW solution exacerbates cold-ischaemia induced endothelial dysfunction. GSNO did not share the detrimental effects of GSH and promoted NO-mediated vasodilatation.
authors.affiliation: Clinical & Surgical Sciences (Surgery), Royal Infirmary of Edinburgh, 51 Little France Crescent, University of Edinburgh, Edinburgh, EH16 4SA, UK. andrew.tambyraja@ed.ac.uk
authors.forename: A L
authors.initials: AL
authors.lastname: Tambyraja
authors.forename: R
authors.initials: R
authors.lastname: Mitchell
authors.forename: P J
authors.initials: PJ
authors.lastname: Driscoll
authors.forename: C
authors.initials: C
authors.lastname: Deans
authors.forename: R W
authors.initials: RW
authors.lastname: Parks
authors.forename: I
authors.initials: I
authors.lastname: Rahman
authors.forename: I L
authors.initials: IL
authors.lastname: Megson
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D050377:Cold Ischemia / Q000379:methods*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005978:Glutathione / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D008297:Male; D019188:Organ Preservation Solutions / Q000494:pharmacology*; D018384:Oxidative Stress; D011887:Raffinose / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D026422:S-Nitrosoglutathione / Q000097:blood / Q000494:pharmacology
chemical_list: D007328:Insulin; D019188:Organ Preservation Solutions; C055206:University of Wisconsin-lactobionate solution; D026422:S-Nitrosoglutathione; D000493:Allopurinol; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose