Increased technetium-99m-GSA uptake per hepatocyte in rats with administration of dimethylnitrosamine or hepatocyte growth factor.
Technetium-99m-diethylenetriaminepentaacetic acid-galactosyl-human serum albumin (GSA) is a new scintigraphic agent that binds specifically to asialoglycoprotein receptors on hepatocytes, and can be used to evaluate hepatic function. Asialoglycoprotein receptor is a hepatocellular membrane receptor responsible for the endocytosis of asialoglycoproteins, and the function of this receptor is affected in various disease states. The aim of this study was to investigate GSA uptake per hepatocyte in the convalescent stage from hepatic damage.


METHODS
We used rats with dimethylnitrosamine (DMN)-induced hepatic injury and rats with recombinant human hepatocyte growth factor (rhHGF) stimulation. Plasma clearance of GSA and the number of hepatocytes in whole liver were calculated.


RESULTS
In the DMN-treated rats, the total number of hepatocytes and GSA plasma clearance were reduced significantly at 3 wk after the final administration of DMN. However, calculated GSA uptake per individual hepatocyte was significantly greater by 53.2% than in the normal controls. The area of hepatic nucleus was also significantly greater than in the normal controls. In the rhHGF-treated rats, an increase in the total number of hepatocytes was not demonstrated on the final day of rhHGF administration (Day 4). However, calculated GSA uptake per hepatocyte was significantly greater (59%) than in the controls.


CONCLUSIONS
Augmented GSA uptake per hepatocyte during the convalescent stage after hepatic injury suggests a cellular compensation to the decreased number of hepatocyte. This mechanism may be caused by the secretion of some hepatotropic factors such as HGF.
Kouda
K
K
Department of Radiology, Kansai Medical University, Moriguchi, Japan.
Ha-Kawa
S K
SK
Tanaka
Y
Y
D000477:Alkylating Agents; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000000981:diagnostic imaging* / Q000209:etiology / Q000473:pathology; D004128:Dimethylnitrosamine; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D008099:Liver / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013668:Technetium Tc 99m Aggregated Albumin / Q000493:pharmacokinetics*; D016284:Technetium Tc 99m Pentetate / Q000493:pharmacokinetics*; D013997:Time Factors
D000477:Alkylating Agents; D019275:Radiopharmaceuticals; D013668:Technetium Tc 99m Aggregated Albumin; C070561:technetium Tc 99m DTPA-galactosyl-human serum albumin; D017228:Hepatocyte Growth Factor; D004128:Dimethylnitrosamine; D016284:Technetium Tc 99m Pentetate