Hydrogen-rich University of Wisconsin solution attenuates renal cold ischemia-reperfusion injury.
BACKGROUND
Renal ischemia-reperfusion (I/R) injury is unavoidable in kidney transplantation and frequently influences both short- and long-term allograft survival rates. One of the major events in I/R injury is the generation of cytotoxic oxygen radicals. Recently, hydrogen gas has been reported to display antioxidant properties and protective effects against organ dysfunction induced by various I/R injuries. We investigated whether hydrogen-rich University of Wisconsin (HRUW) solution attenuates renal cold I/R injury.


METHODS
We prepared HRUW solution by a novel method involving immersion of centrifuge tubes containing UW solution into hydrogen-saturated water. Hydrogen readily permeates through the centrifuge tubes, and thus, the hydrogen concentration of the UW solution gradually increases in a time-dependent manner. Syngeneic rat kidney transplantation was performed, and the animals were divided into three groups: recipients with nonpreserved grafts (control group), recipients with grafts preserved in UW solution for 24 to 48 hr (UW group), and recipients with grafts preserved in HRUW solution for 24 to 48 hr (HRUW group).


RESULTS
In the early phases, HRUW solution decreased oxidative stress, tubular apoptosis, and interstitial macrophage infiltration in the kidney grafts. Consequently, HRUW solution improved renal function and prolonged recipient survival rate compared with simple cold storage using UW solution. Histopathologically, HRUW treatment alleviated tubular injury and suppressed development of interstitial fibrosis.


CONCLUSIONS
HRUW solution improved graft function and prolonged graft survival compared with simple cold storage using UW solution by protecting tubular epithelial cells from inflammation and apoptosis. Our new method of organ preservation is a groundbreaking, safe, and simple strategy that may be applied in the clinical setting.
Department of Specific Organ Regulation (Urology), Graduate School of Medicine, Osaka University, Osaka, Japan.
Toyofumi
T
Abe
Xiao-Kang
XK
Li
Koji
K
Yazawa
Naoyuki
N
Hatayama
Lin
L
Xie
Bunpei
B
Sato
Yoichi
Y
Kakuta
Koichi
K
Tsutahara
Masayoshi
M
Okumi
Hidetoshi
H
Tsuda
Jun-ya
JY
Kaimori
Yoshitaka
Y
Isaka
Michiya
M
Natori
Shiro
S
Takahara
Norio
N
Nonomura
D000241:Adenosine / Q000494:pharmacology; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D003080:Cold Temperature; D005978:Glutathione / Q000494:pharmacology; D006085:Graft Survival; D006859:Hydrogen / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply*; D016030:Kidney Transplantation; D007684:Kidney Tubules / Q000473:pathology; D008264:Macrophages / Q000502:physiology; D008297:Male; D019188:Organ Preservation Solutions / Q000494:pharmacology*; D018384:Oxidative Stress; D011887:Raffinose / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000517:prevention & control*; D015996:Survival Rate
D007328:Insulin; D019188:Organ Preservation Solutions; C055206:University of Wisconsin-lactobionate solution; D000493:Allopurinol; D006859:Hydrogen; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose