title: UW solution improved with high anti-apoptotic activity by S-nitrosated human serum albumin.
abstract: S-Nitrosated human serum albumin (SNO-HSA) is useful in preventing liver ischemia/reperfusion injury, and SNO-HSA should thus be able to prevent cell injury during liver transplantation. However, the potential protective effect of SNO-HSA on a combination of cold and warm ischemia, which is obligatory when performing liver transplantation, has not been examined. Therefore, we evaluated the protective effect of SNO-HSA added to University of Wisconsin (UW) solution during cold or/and warm ischemia in situ and in vitro. First, we observed that apoptotic and necrotic cell death were increased during cold and warm ischemia, respectively. SNO-HSA, which possesses anti-apoptosis activity at low NO concentrations, can inhibit cold ischemia injury both in situ and in vitro. In contrast, SNO-HSA had no significant effect on warm liver ischemia injury which, however, can be reduced by UW solution. We also demonstrated that the cellular uptake of NO from SNO-HSA can occur during cold ischemia resulting in induction of heme oxygenase-1 within 3h of cold ischemia. Our results indicate that treatment with SNO-HSA or UW solution alone is not sufficient to inhibit liver injury during a period of both cold and warm ischemia. However, a combination of SNO-HSA and UW solution can be used to prevent the two types of ischemia. SNO-HSA-added UW solution could be very useful in transplantation, because the previously imposed constraints on preservation time can be removed. This is a great advantage in a situation as the present one with increased utilization of scarce donor organs for more recipients.
authors: Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan.
authors: Yu
authors: Y
authors: Ishima
authors: Takuya
authors: T
authors: Shinagawa
authors: Shinji
authors: S
authors: Yoneshige
authors: Ulrich
authors: U
authors: Kragh-Hansen
authors: Yuki
authors: Y
authors: Ohya
authors: Yukihiro
authors: Y
authors: Inomata
authors: Toshiya
authors: T
authors: Kai
authors: Masaki
authors: M
authors: Otagiri
authors: Toru
authors: T
authors: Maruyama
mesh_terms: D000241:Adenosine / Q000737:chemistry / Q000494:pharmacology; D000493:Allopurinol / Q000737:chemistry / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D005978:Glutathione / Q000737:chemistry / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D007328:Insulin / Q000737:chemistry / Q000494:pharmacology; D008099:Liver / Q000098:blood supply* / Q000166:cytology / Q000187:drug effects; D008107:Liver Diseases / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D016031:Liver Transplantation / Q000379:methods*; D008297:Male; D009336:Necrosis; D020030:Nitric Oxide Donors / Q000737:chemistry / Q000494:pharmacology; D009603:Nitroso Compounds / Q000737:chemistry / Q000494:pharmacology*; D019188:Organ Preservation Solutions / Q000737:chemistry / Q000494:pharmacology*; D011887:Raffinose / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D012709:Serum Albumin / Q000737:chemistry / Q000494:pharmacology*; D000075462:Serum Albumin, Human
chemical_list: D007328:Insulin; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D019188:Organ Preservation Solutions; C511514:S-nitrosoalbumin, human; D012709:Serum Albumin; C055206:University of Wisconsin-lactobionate solution; D000493:Allopurinol; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose; D000075462:Serum Albumin, Human