Evaluation of asialoglycoprotein receptor imaging agent as a marker of hepatic ischemia-reperfusion injury and recovery

Abstract

Protection of hepatocytes from ischemia-reperfusion injury is a clinically important issue. The purpose of this study was to evaluate changes in acute liver damage and recovery after ischemia-reperfusion in rats with asialoglycoprotein receptor (ASGP-R) ligand. Ischemia was induced by clamping the hepatoduodenal ligament for 90 min. At 1, 3, 24, 48 hr, 1 and 2 wk after reperfusion, I-125-GSA was injected. Five min after injection, blood samples were obtained and the liver was removed. Several regions from each lobe were dissected, weighed and counted. Mean uptakes (% dose/g) in the liver and blood samples were calculated. Histologic sections stained with hematoxylin-eosin (H-E) stain showed ischemic damage at 1 and 3 hr, and focal hepatocyte necrosis at 24 hr. Predominant massive necrosis was not seen. The mitotic index with H-E stain and proliferating cell nuclear antigen (PCNA) labeling index were highest at 1 wk, indicating liver regeneration. At 1 and 3 hr, liver uptake was significantly decreased, and blood uptake was significantly increased, indicating decreased tissue blood flow and ischemic damage. Liver uptake showed significant increases at 48 hr and 1 wk, and was the highest at 1 wk, indicating liver regeneration during the convalescence stage. ASGP-R binding may provide valuable information on ischemia-reperfusion injury and recovery.

Prometheus’ Challenge: Molecular, Cellular and Systemic Aspects of Liver Regeneration

“…Soon after, they mediate the activation of platelet adhesion and neutrophil inflammatory response that infiltrates the injured liver and increases the expression of more adhesion molecules on endothelial cells and more generation of reactive oxygen radicals. The methods by which ischemia/reperfusion injury can be diagnosed include ASGP-R ligand on hepatocytes, showing ischemic damage histologically, hepatobiliary scintigraphy, an easy method in clinics, and electron microscopy, the diagnostic gold standard [135][136][137][138][139][140][141][142][143][144][145]. Reactive oxygen radical scavengers can be used to protect ischemia/reperfusion injury syndrome.…”

Imaging of liver function with dedicated animal dynamic pinhole scintigraphy in rats

“…The horizontal broken line indicates the 95% confidence interval based on the normal values (Table 1). Studies have been performed to estimate the hepatic functional reserve using 99m Tc-diethylenetriaminepentaacetic acid-99m Tc-galactosyl human serum albumin ( 99m Tc-DTPA-99m Tc-GSA) liver scintigraphy in rats [25,26]. 99m Tc-GSA is a liver scintigraphy agent that binds to the asialoglycoprotein receptor on hepatocytes [27].…”