ALA and ALA hexyl ester induction of porphyrins after their systemic administration to tumour bearing mice.
The use of synthetic lipophilic molecules derived from 5-aminolevulinic acid (ALA) is currently under investigation to enhance cellular ALA penetration. In this work we studied the effect of systemic administration to mice of the hexyl ester of ALA (He-ALA) on porphyrin tissue synthesis as compared to ALA. In most normal tissues as well as in tumour, He-ALA induced less porphyrin synthesis than ALA after its systemic administration either intravenous or intraperitoneal, although explant organ cultures exposed to either ALA or He-ALA revealed equally active esterases. The only tissue that accumulated higher porphyrin levels from He-ALA (seven times more than ALA) was the brain, and this correlated well with a rapid increase in ALA/He-ALA content in brain after administration of He-ALA. This may be ascribed to a differential permeability to lipophilic substances controlled by the blood-brain barrier, a feature which could be further exploited to treat brain tumours.
Perotti
C
C
Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP), CONICET and Department of Biochemistry, School of Sciences, University of Buenos Aires, Argentine.
Casas
A
A
Fukuda
H
H
Sacca
P
P
Batlle
A
A
D000622:Aminolevulinic Acid / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000378:metabolism; D009928:Organ Specificity; D011166:Porphyrins / Q000032:analysis / Q000096:biosynthesis*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D011166:Porphyrins; D000622:Aminolevulinic Acid