Takanobu Shigeta1, Seisuke Sakamoto, Xiao-Kang Li, Songjie Cai, Chi Liu, Ryosuke Kurokawa, Atsuko Nakazawa, Mureo Kasahara, Shinji Uemoto. 1. 1 Organ Transplant Center, National Center for Child Health and Development, Tokyo, Japan. 2 Division of Hepato-Biliary-Pancretic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan. 3 Division of Transplantation Immunology, National Research Institute for Child Health and Development, Tokyo, Japan. 4 MiZ Co., Ltd., Kanagawa, Japan. 5 Department of Clinical Pathology, National Center for Child Health and Development, Tokyo, Japan.
Abstract
BACKGROUND: Luminal preservation of the intestine is an attractive method to locally mitigate preservation injury and ischemic-reperfusion injury in small bowel transplantation (SBT) because this method has a potential to maintain the intestinal graft integrity. Hydrogen is noted as an antioxidant material by reducing hydroxyl radicals. We hypothesized that hydrogen-containing solution can be an optimum material for luminal preservation method in SBT. METHODS: Ischemic reperfusion was induced in Lewis rats by occlusion of the supramesenteric artery and vein for 90 min. Experimental protocols were divided into four groups: sham operation group, no luminal injection (control) group, luminal injection of 5% glucose saline (GS) solution group, and luminal injection of hydrogen-rich GS (HRGS) group. Two milliliters of experimental solution was locally injected into the lumen of the intestine before declamping of vessels. Oxidative stress markers, proinflammatory cytokines, apoptosis in the crypt cells, and morphologic changes of the intestine were assessed. RESULTS: The production of malondialdehyde and 8-hydroxydeoxyguanosine, as oxidative stress markers, were markedly suppressed in HRGS group. The level of proinflammatory cytokines, such as inducible nitric oxide synthase and interleukin-6, was significantly inhibited in HRGS group. Crypt apoptosis was also significantly suppressed in HRGS group. Histopathologically, integrity of villus in intestine was maintained in HRGS group in comparison to the other groups. CONCLUSION: Luminal injection of hydrogen-rich solution can reduce oxidative stress and consequently ameliorate ischemic-reperfusion injury. Hydrogen-containing solution can be a novel and promising luminal preservation material in SBT.
BACKGROUND: Luminal preservation of the intestine is an attractive method to locally mitigate preservation injury and ischemic-reperfusion injury in small bowel transplantation (SBT) because this method has a potential to maintain the intestinal graft integrity. Hydrogen is noted as an antioxidant material by reducing hydroxyl radicals. We hypothesized that hydrogen-containing solution can be an optimum material for luminal preservation method in SBT. METHODS: Ischemic reperfusion was induced in Lewis rats by occlusion of the supramesenteric artery and vein for 90 min. Experimental protocols were divided into four groups: sham operation group, no luminal injection (control) group, luminal injection of 5% glucose saline (GS) solution group, and luminal injection of hydrogen-rich GS (HRGS) group. Two milliliters of experimental solution was locally injected into the lumen of the intestine before declamping of vessels. Oxidative stress markers, proinflammatory cytokines, apoptosis in the crypt cells, and morphologic changes of the intestine were assessed. RESULTS: The production of malondialdehyde and 8-hydroxydeoxyguanosine, as oxidative stress markers, were markedly suppressed in HRGS group. The level of proinflammatory cytokines, such as inducible nitric oxide synthase and interleukin-6, was significantly inhibited in HRGS group. Crypt apoptosis was also significantly suppressed in HRGS group. Histopathologically, integrity of villus in intestine was maintained in HRGS group in comparison to the other groups. CONCLUSION: Luminal injection of hydrogen-rich solution can reduce oxidative stress and consequently ameliorate ischemic-reperfusion injury. Hydrogen-containing solution can be a novel and promising luminal preservation material in SBT.
Authors: Sara Franceschelli; Daniela Maria Pia Gatta; Mirko Pesce; Alessio Ferrone; Giuseppe Di Martino; Marta Di Nicola; Maria Anna De Lutiis; Ester Vitacolonna; Antonia Patruno; Alfredo Grilli; Mario Felaco; Lorenza Speranza Journal: J Cell Mol Med Date: 2018-03-07 Impact factor: 5.310