Doxorubicin coupled to lactosaminated albumin: Effects on rats with liver fibrosis and cirrhosis.
BACKGROUND
The conjugate of doxorubicin with lactosaminated human albumin has the potential of increasing the doxorubicin efficacy in the treatment of hepatocellular carcinomas expressing the asialoglycoprotein receptor. However, coupled doxorubicin also accumulates in the liver, which might damage hepatocytes.


OBJECTIVE
To verify whether coupled doxorubicin impairs liver function in rats with liver fibrosis and cirrhosis.


METHODS
Coupled doxorubicin was administered using the same schedule which exerted an antineoplastic effect on rat hepatocellular carcinomas (4-weekly injections of doxorubicin at 1 microg/g). Liver fibrosis/cirrhosis was produced by carbon tetrachloride (CCl4) poisoning. Liver samples were studied histologically. Serum parameters of liver function and viability were determined.


RESULTS
In normal rats, administration of coupled doxorubicin neither caused microscopic changes of hepatocytes nor modified serum liver parameters. In rats with fibrosis/cirrhosis, although a selective doxorubicin accumulation within the liver followed coupled doxorubicin administration, the drug did not have a detrimental effect on the histology of the liver and, among serum liver tests, only alanine aminotransferase and aspartate aminotransferase levels were moderately modified.


CONCLUSIONS
Coupled doxorubicin can be administered to rats with liver fibrosis/cirrhosis without inducing a severe liver damage. If further studies will confirm the efficacy and safety of this compound, coupled doxorubicin therapy may open a new perspective in the treatment of hepatocellular carcinoma.
Di Stefano
G
G
Department of Experimental Pathology, University of Bologna, Via San Giacomo 14, 40126 Bologna, Italy.
Fiume
L
L
Domenicali
M
M
Busi
C
C
Chieco
P
P
Kratz
F
F
Lanza
M
M
Mattioli
A
A
Pariali
M
M
Bernardi
M
M
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity*; D004337:Drug Carriers; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism*; D008113:Liver Neoplasms / Q000188:drug therapy; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin
D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D012709:Serum Albumin; C046912:lactosaminated serum albumin; D004317:Doxorubicin