title: Liver-targeted doxorubicin: effects on rat regenerating hepatocytes.
abstract: OBJECTIVE
  The conjugate of doxorubicin (DOXO) with lactosaminated human albumin (L-HSA) has the potential of improving DOXO efficacy in the treatment of hepatocellular carcinomas (HCCs) expressing the asialoglycoprotein receptor (ASGP-R). In view of an adjuvant chemotherapy with L-HSA-DOXO after the surgical removal of the tumour, in the present experiments we verified whether DOXO accumulation produced by the conjugate can impair the liver regeneration following hepatic resection in non-cirrhotic liver.
  
  
  METHODS
  Using saline-injected hepatectomised rats as controls, we studied the effects of the conjugate on the ultrastructure of regenerating hepatocytes and evaluated [3H]thymidine incorporation, mitotic index and rate of DNA recovery in the liver remnant.
  
  
  RESULTS
  L-HSA-DOXO caused a selective drug accumulation in liver remnant, with low DOXO levels in extra-hepatic tissues. It did not change the ultrastructure of hepatocytes and did not increase serum alanine aminotransferase. It decreased [3H]thymidine incorporation and mitotic index, causing a moderate delay in hepatic DNA recovery.
  
  
  CONCLUSIONS
  The experiments indicate a substantial resistance of rat regenerating hepatocytes to high intracellular concentrations of DOXO. They support the possibility of using L-HSA-DOXO in an adjuvant chemotherapy after the surgical removal of HCCs which maintain the ASGP-R.
authors.affiliation: Department of Experimental Pathology, University of Bologna, Via San Giacomo, Bologna, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Di Stefano
authors.forename: Massimo
authors.initials: M
authors.lastname: Derenzini
authors.forename: Felix
authors.initials: F
authors.lastname: Kratz
authors.forename: Marcella
authors.initials: M
authors.lastname: Lanza
authors.forename: Luigi
authors.initials: L
authors.lastname: Fiume
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics / Q000494:pharmacology*; D004247:DNA / Q000302:isolation & purification; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000494:pharmacology*; D004338:Drug Combinations; D004357:Drug Synergism; D006498:Hepatectomy; D022781:Hepatocytes / Q000502:physiology* / Q000648:ultrastructure; D006801:Humans; D008099:Liver / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D008940:Mitotic Index; D009994:Osmolar Concentration; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; D004338:Drug Combinations; D012709:Serum Albumin; C046912:lactosaminated serum albumin; D004317:Doxorubicin; D004247:DNA; D000410:Alanine Transaminase; D013936:Thymidine