title: Amifostine enhances the antioxidant and hepatoprotective effects of UW and HTK preservation solutions.
abstract: OBJECTIVE
  To investigate whether amifostine contributes to the antioxidant and cytoprotective effects of histidine-tryptophan-ketoglutarate (HTK) and University of Wisconsin (UW) preservation solutions.
  
  
  METHODS
  Forty-eight Sprague Dawley male rats were equally divided into six groups: (1) ringer Lactate (RL) group; (2) RL + amifostine (RL + A) group; (3) HTK group; (4) HTK + A group; (5) UW group; and (6) UW + A group. Rats in the RL + A, HTK + A and UW + A groups were administered amifostine intraperitoneally at a dose of 200 mg/kg prior to laparotomy. The RL group was perfused with RL into the portal vein. The RL + A group were perfused with RL into the portal vein after amifostine administration. The HTK group received an HTK perfusion while the HTK + A group received an HTK perfusion after administration of amifostine. The UW group received a perfusion of UW, while the UW + A group received a UW perfusion after amifostine administration. Liver biopsy was performed to investigate histopathological, immunochemical [transferase mediated dUTP nick end labeling (TUNEL), inducible nitric oxide syntetase (iNOS)] and ultrastructural alterations. Biochemical alterations were determined by examining levels of alanine aminotransferase, alkaline phosphatase and nitric oxide in the perfusion fluid.
  
  
  RESULTS
  Pathological sinusoidal dilatation and centrilobular hydropic alteration were significantly lower in the groups that received amifostine prior to preservation solution perfusion. Although the best results were obtained in the UW + A group, we did not observe a statistically significant difference between the UW + A and HTK + A groups. iNOS grades were significantly lower in the amifostine groups 12 h after treatment. When the amifostine groups were compared against each other, the iNOS grades obtained from the UW + A and HTK + A groups were similar while the RL + A group had a much poorer score. TUNEL assays demonstrated a lower apoptosis ratio in the amifostine groups than in the non-amifostine groups 12 h after treatment. No statistically significant difference was observed between the UW + A and HTK + A groups for apoptosis. Cellular ultrastructure was best preserved in the UW + A and HTK + A groups.
  
  
  CONCLUSIONS
  Here, we show that preoperative administration of a single dose of amifostine is sufficient to minimize the preservation damage in hepatic cells.
authors.affiliation: Sami Akbulut, Department of Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, Turgut Ozal Medical Center, Malatya 44280, Turkey.
authors.forename: Sami
authors.initials: S
authors.lastname: Akbulut
authors.affiliation: Sami Akbulut, Department of Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, Turgut Ozal Medical Center, Malatya 44280, Turkey.
authors.forename: Sinasi
authors.initials: S
authors.lastname: Sevmis
authors.affiliation: Sami Akbulut, Department of Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, Turgut Ozal Medical Center, Malatya 44280, Turkey.
authors.forename: Hamdi
authors.initials: H
authors.lastname: Karakayali
authors.affiliation: Sami Akbulut, Department of Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, Turgut Ozal Medical Center, Malatya 44280, Turkey.
authors.forename: Nilüfer
authors.initials: N
authors.lastname: Bayraktar
authors.affiliation: Sami Akbulut, Department of Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, Turgut Ozal Medical Center, Malatya 44280, Turkey.
authors.forename: Muge
authors.initials: M
authors.lastname: Unlukaplan
authors.affiliation: Sami Akbulut, Department of Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, Turgut Ozal Medical Center, Malatya 44280, Turkey.
authors.forename: Ergun
authors.initials: E
authors.lastname: Oksuz
authors.affiliation: Sami Akbulut, Department of Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, Turgut Ozal Medical Center, Malatya 44280, Turkey.
authors.forename: Atilla
authors.initials: A
authors.lastname: Dagdeviren
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000410:Alanine Transaminase / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D000493:Allopurinol / Q000494:pharmacology; D004999:Amifostine / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D050377:Cold Ischemia / Q000009:adverse effects*; D019610:Cytoprotection; D004357:Drug Synergism; D005947:Glucose / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology; D006498:Hepatectomy; D020287:In Situ Nick-End Labeling; D007328:Insulin / Q000494:pharmacology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D046529:Microscopy, Electron, Transmission; D023421:Models, Animal; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009926:Organ Preservation / Q000379:methods*; D019188:Organ Preservation Solutions / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D011343:Procaine / Q000494:pharmacology; D011887:Raffinose / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D000975:Antioxidants; D015415:Biomarkers; C039984:Bretschneider cardioplegic solution; D007328:Insulin; D019188:Organ Preservation Solutions; C055206:University of Wisconsin-lactobionate solution; D009569:Nitric Oxide; D008353:Mannitol; D011343:Procaine; D000493:Allopurinol; D011189:Potassium Chloride; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D005978:Glutathione; D005947:Glucose; D000241:Adenosine; D004999:Amifostine; D011887:Raffinose
keywords: Amifostine; Antioxidant; Histidine-tryptophan-ketoglutarate; Liver; Preservation solutions; Transplantation; University of Wisconsin