Resealed erythrocyte ghosts are potential in vivo carriers of exogenous therapeutic enzymes. In the present work, the effect of administering δ-aminolaevulinate dehydratase (ALA-D) encapsulated in autologous red blood cell ghosts (RBCg) to lead intoxicated and normal mice was investigated. Administration of ALA-D loaded RBCg to intoxicated mice produced an immediate and permanent recovery in erythrocytic ALA-D activity; the effect was also noticeable in liver and spleen and absent in kidney, indicating that the entrapped enzyme was significantly stabilized to allow retention of activity in both circulating and phagocytized cells. Administration of ALA-D loaded ghosts to normal mice did not produce significant changes in ALA-D activity in blood, liver, spleen or kidney. Administration of free exogenous enzyme or blood transfusion during lead intoxication was also ineffective; spontaneous recovery of the poisoned animals was very slow. We show that circulating as well as phagocytized ALA-D entrapped in autologous erythrocyte ghosts can be safe and beneficial in the treatment of lead poisoning. Clinical trial in patients is recommended.
Documento: | Artículo |
Título: | Enzyme replacement therapy in porphyrias. V. In vivo correction of δ-aminolaevulinate dehydratase defective in erythrocytes in lead intoxicated animals by enzyme-loaded red blood cell ghosts |
Autor: | Bustos, N.L.; Del Batlle, C.A.M. |
Filiación: | Cent. Invest. sobre Porfirinas, University of Buenos Aires, Ciudad Universitaria, Pabellon II, 1428 Buenos Aires, Argentina |
Palabras clave: | Aminolevulic acid dehydratase; Enzyme replacement therapy; Lead intoxication; Porphyrias; Red blood cell ghosts; porphobilinogen synthase; animal experiment; animal model; article; autologous blood; bioavailability; blood level; congenital disorder; erythrocyte ghost; head; intoxication; intravenous drug administration; kidney; liver; mouse; nonhuman; porphyria; priority journal; spleen; Animal; Erythrocyte Membrane; Erythrocytes; Female; Lead Poisoning; Mice; Mice, Inbred Strains; Porphobilinogen Synthase; Porphyria; Support, Non-U.S. Gov't |
Año: | 1989 |
Volumen: | 5 |
Número: | 2 |
Página de inicio: | 125 |
Página de fin: | 131 |
Título revista: | Drug Design and Delivery |
Título revista abreviado: | DRUG DES. DELIV. |
ISSN: | 08842884 |
CODEN: | DDDEE |
CAS: | porphobilinogen synthase, 9036-37-7; Porphobilinogen Synthase, EC 4.2.1.24 |
Registro: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_08842884_v5_n2_p125_Bustos |