Randomized Controlled Trial
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World J Gastroenterol. Sep 14, 2014; 20(34): 12292-12300
Published online Sep 14, 2014. doi: 10.3748/wjg.v20.i34.12292
Amifostine enhances the antioxidant and hepatoprotective effects of UW and HTK preservation solutions
Sami Akbulut, Sinasi Sevmis, Hamdi Karakayali, Nilüfer Bayraktar, Muge Unlukaplan, Ergun Oksuz, Atilla Dagdeviren
Sami Akbulut, Department of Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, Turgut Ozal Medical Center, Malatya 44280, Turkey
Sinasi Sevmis, Hamdi Karakayali, Department of Surgery and Organ Transplantation, Medipol University Faculty of Medicine, Medipol Mega Hospital, Istanbul 34214, Turkey
Nilüfer Bayraktar, Department of Biochemistry, Baskent University Faculty of Medicine, Ankara 06810, Turkey
Muge Unlukaplan, Department of Pathology, Darica Farabi State Hospital, Kocaeli 41700, Turkey
Ergun Oksuz, Family Medicine Unit, Medicosocial Health Center, Baskent University Faculty of Medicine, Ankara 06810, Turkey
Atilla Dagdeviren, Department of Histology and Embryology, Baskent University Faculty of Medicine, Ankara 06810, Turkey
Author contributions: The experiments proposed in this study are derived from the thesis work of Akbulut S; Sevmis S and Karakayali H advised the thesis of Akbulut S; Akbulut S and Sevmis S performed all experiments and surgical procedures; Akbulut S wrote the paper and reviewed the literature; Unlukaplan M provided the histopathological information; Dagdeviren A provided the electron microscopy information; Bayraktar N provided biochemical information; Oksuz E performed all statistical analyses.
Correspondence to: Sami Akbulut, Associate Professor, FICS, FACS, Department of Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, Turgut Ozal Medical Center, Malatya 44280, Turkey. akbulutsami@gmail.com
Telephone: +90-422-3410660 Fax: +90-422-3410036
Received: November 20, 2013
Revised: March 7, 2014
Accepted: April 28, 2014
Published online: September 14, 2014
Processing time: 302 Days and 14.8 Hours
Abstract

AIM: 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.

CONCLUSION: Here, we show that preoperative administration of a single dose of amifostine is sufficient to minimize the preservation damage in hepatic cells.

Keywords: Liver; Transplantation; Preservation solutions; Histidine-tryptophan-ketoglutarate; University of Wisconsin; Antioxidant; Amifostine

Core tip: Preserving liver tissue obtained from a donor until implantation is a critical step that affects how the graft will function. Many different organ preservation solutions have been introduced over the last quarter century, and histidine-tryptophan-ketoglutarate (HTK) and University of Wisconsin (UW) are currently the most commonly used solutions in clinical practice. Because neither the HTK nor UW solution is ideal, many studies have focused on methods to enhance the antioxidant and cytoprotective effects of the preservation solutions. In this study, we investigated whether amifostine could boost the antioxidant and cytoprotective effects of HTK and UW preservation solutions.