TY - JOUR
T1 - New drug delivery system for liver sinusoidal endothelial cells for ischemia-reperfusion injury
AU - Sano, Naoki
AU - Tamura, Takafumi
AU - Toriyabe, Naoyuki
AU - Nowatari, Takeshi
AU - Nakayama, Ken
AU - Tanoi, Tomohito
AU - Murata, Soichiro
AU - Sakurai, Yu
AU - Hyodo, Mamoru
AU - Fukunaga, Kiyoshi
AU - Harashima, Hideyoshi
AU - Ohkohchi, Nobuhiro
N1 - Publisher Copyright:
© The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
PY - 2015/12/7
Y1 - 2015/12/7
N2 - AIM: To investigate the cytoprotective effects in hepatic ischemia-reperfusion injury, we developed a new formulation of hyaluronic acid (HA) and sphingosine 1-phophate. METHODS: We divided Sprague-Dawley rats into 4 groups: control, HA, sphingosine 1-phosphate (S1P), and HA-S1P. After the administration of each agent, we subjected the rat livers to total ischemia followed by reperfusion. After reperfusion, we performed the following investigations: alanine aminotransferase (ALT), histological findings, TdT-mediated dUTP-biotin nick end labeling (TUNEL) staining, and transmission electron microscopy (TEM). We also investigated the expression of proteins associated with apoptosis, hepatoprotection, and S1P accumulation. RESULTS: S1P accumulated in the HA-S1P group livers more than S1P group livers. Serum ALT levels, TUNEL-positive hepatocytes, and expression of cleaved caspase-3 expression, were significantly decreased in the HA-S1P group. TEM revealed that the liver sinusoidal endothelial cell (LSEC) lining was preserved in the HA-S1P group. Moreover, the HA-S1P group showed a greater increase in the HO-1 protein levels compared to the S1P group. CONCLUSION: Our results suggest that HA-S1P exhibits cytoprotective effects in the liver through the inhibition of LSEC apoptosis. HA-S1P is an effective agent for hepatic ischemia/reperfusion injury.
AB - AIM: To investigate the cytoprotective effects in hepatic ischemia-reperfusion injury, we developed a new formulation of hyaluronic acid (HA) and sphingosine 1-phophate. METHODS: We divided Sprague-Dawley rats into 4 groups: control, HA, sphingosine 1-phosphate (S1P), and HA-S1P. After the administration of each agent, we subjected the rat livers to total ischemia followed by reperfusion. After reperfusion, we performed the following investigations: alanine aminotransferase (ALT), histological findings, TdT-mediated dUTP-biotin nick end labeling (TUNEL) staining, and transmission electron microscopy (TEM). We also investigated the expression of proteins associated with apoptosis, hepatoprotection, and S1P accumulation. RESULTS: S1P accumulated in the HA-S1P group livers more than S1P group livers. Serum ALT levels, TUNEL-positive hepatocytes, and expression of cleaved caspase-3 expression, were significantly decreased in the HA-S1P group. TEM revealed that the liver sinusoidal endothelial cell (LSEC) lining was preserved in the HA-S1P group. Moreover, the HA-S1P group showed a greater increase in the HO-1 protein levels compared to the S1P group. CONCLUSION: Our results suggest that HA-S1P exhibits cytoprotective effects in the liver through the inhibition of LSEC apoptosis. HA-S1P is an effective agent for hepatic ischemia/reperfusion injury.
KW - Drug delivery system
KW - Heme oxygenase-1
KW - Hyaluronic acid
KW - Liver sinusoidal endothelial cell
KW - Sphingosine 1-phosphate
KW - Stabilin-2
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U2 - 10.3748/wjg.v21.i45.12778
DO - 10.3748/wjg.v21.i45.12778
M3 - Article
C2 - 26668502
AN - SCOPUS:84948965188
SN - 1007-9327
VL - 21
SP - 12778
EP - 12786
JO - World Journal of Gastroenterology
JF - World Journal of Gastroenterology
IS - 45
ER -