Al-Shabanah O A, Badary O A, Al-Gharably N M, Al-Sawaf H A
Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Pharmacol Res. 1998 Sep;38(3):225-30. doi: 10.1006/phrs.1998.0355.
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.
L-组氨醇（LHL）是必需氨基酸L-组氨酸的结构类似物，可提高抗代谢物和烷化剂的治疗指数。本研究的目的是确定LHL是否会调节蒽环类抗生素阿霉素（DOX）的抗肿瘤活性和急性心脏毒性。LHL（1.0 mM）增强了DOX（0.05 - 0.8微克/毫升）对培养的艾氏腹水癌（EAC）细胞的细胞毒性。在DOX（5毫克/千克，腹腔注射）单次注射前2小时开始，以2小时间隔连续五次腹腔注射LHL（250毫克/千克），可增强DOX对荷EAC小鼠的抗肿瘤活性，表现为小鼠平均寿命和治愈率显著提高。在正常小鼠中，相同剂量方案的LHL不会改变DOX（10毫克/千克，腹腔注射）的急性心脏毒性和致死率。目前的数据表明，LHL可能提高DOX对荷EAC小鼠的治疗效果而不影响其毒性。此外，我们的发现支持LHL/抗癌药物联合应用方法。
