Effects of L-histidinol on the antitumour activity and acute cardiotoxicity of doxorubicin in mice

L-Histidinol (LHL), a structural analogue of the essential amino acid l-histidine, can improve the therapeutic index of antimetabolites and alkylating agents. The objective of the study was to determine whether LHL would modulate the antitumour activity and acute cardiotoxicity of the anthracycline...

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Bibliographic Details
Published in:Pharmacological research 1998-09, Vol.38 (3), p.225
Main Authors: Al-Shabanah, O A, Badary, O A, Al-Gharably, N M, Al-Sawaf, H A
Format: Article
Language:English
Subjects:
Animals
Antibiotics, Antineoplastic - pharmacology
Carcinoma, Ehrlich Tumor - drug therapy
Cell Survival - drug effects
Dose-Response Relationship, Drug
Doxorubicin - pharmacology
Doxorubicin - toxicity
Drug Synergism
Female
Heart - drug effects
Histidinol - pharmacology
Mice
Tumor Cells, Cultured
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Summary:L-Histidinol (LHL), a structural analogue of the essential amino acid l-histidine, can improve the therapeutic index of antimetabolites and alkylating agents. The objective of the study was to determine whether LHL would modulate the antitumour activity and acute cardiotoxicity of the anthracycline antibiotic, doxorubicin (DOX). LHL (1.0 mM) potentiated the cytotoxicity of DOX (0.05-0.8 microg ml-1) in cultured Ehrlich ascites carcinoma (EAC) cells. LHL (250 mg kg-1, i.p.) administered for five consecutive doses at 2-h intervals starting 2 h before DOX (5 mg kg-1, i.p.) single injection, enhanced the antitumour activity of DOX in EAC-bearing mice as manifested by a significant increase in average life span and cure rate of mice. In normal mice, LHL, in the same dose regimen, could not alter the acute cardiotoxicity and lethality of DOX (10 mg kg-1, i.p.). The present data indicate that LHL may improve the therapeutic efficacy of DOX in EAC-bearing mice without compromising its toxicity. Also, our finding supports the LHL/anticancer drug combination approach.
ISSN:1043-6618
DOI:10.1006/phrs.1998.0355