L-Histidinol is an intermediate in the biosynthesis of the amino acid L-histidine.
L-Histidine biosynthesis is a metabolic pathway present in bacteria, archaea, lower eukaryotes, as well as plants. L-histidine biosynthesis has been studied mainly in Escherichia coli and Salmonella typhimurium, revealing fundamental regulatory processes in bacteria.
In vitro: Preliminary experiments were done to investigate the cytotoxic effect of L-histidinol on cultured EAC cells. Results showed that L-histidinol up to 4 mM had no cytotoxic effects on EAC cells. Doxorubicin alone showed concentration-dependent cytotoxic effects. L-Histidinol combination with doxorubicin led to significant potentiation of doxorubicin cytotoxicity to EAC cells compared to doxorubicin alone. The concentration that caused 50% growth inhibition in EAC cells after 24 h incubation was about 0.2 μg/ml, whereas it was 0.1 μg/ml when L-histidinol was added to culture medium [1].
In vivo: L-Histidinol at 250 mg/kg for five consecutive doses before doxorubicin single injection could enhance the antitumour activity of doxorubicin in EAC-bearing mice as demonstrated by a significant increase in average life span and cure rate of mice. In normal mice, L-histidinol, in the same dose regimen, could not alter the acute cardiotoxicity and lethality of doxorubicin [1].
Clinical trial: So far, no clinical study has been conducted.
Reference:
[1] Al-Shabanah OA, Badary OA, Al-Gharably NM, Al-Sawaf HA. Effects of L-histidinol on the antitumour activity and acute cardiotoxicity of doxorubicin in mice. Pharmacol Res. 1998 Sep;38(3):225-30.