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Updated: Mar 28, 2026
Method of Direct Segmental Intra-hepatic Delivery Using a Rat Liver Hilar Clamp Model
Published on: April 2, 2017
New drug delivery system for liver sinusoidal endothelial cells for ischemia-reperfusion injury
Naoki Sano1, Takafumi Tamura1, Naoyuki Toriyabe1
1Naoki Sano, Takafumi Tamura, Takeshi Nowatari, Ken Nakayama, Tomohito Tanoi, Soichiro Murata, Kiyoshi Fukunaga, Nobuhiro Ohkohchi, Department of Surgery, Doctoral Program in Clinical Science, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba 305-8575, Japan.
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.
