Enzyme replacement therapy in porphyrias--V. In vivo correction of delta-aminolaevulinate dehydratase defective in erythrocytes in lead intoxicated animals by enzyme-loaded red blood cell ghosts.
Resealed erythrocyte ghosts are potential in vivo carriers of exogenous therapeutic enzymes. In the present work, the effect of administering delta-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.
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Centro de Investigaciones sobre Porfirinas y Porfirias CIPYP-(CONICET & FCEN, University of B. Aires)-Ciudad Universitaria, Argentine.
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D000818:Animals; D004910:Erythrocyte Membrane / Q000201:enzymology*; D004912:Erythrocytes / Q000201:enzymology*; D005260:Female; D007855:Lead Poisoning / Q000097:blood / Q000188:drug therapy*; D051379:Mice; D008815:Mice, Inbred Strains; D000623:Porphobilinogen Synthase / Q000097:blood / Q000172:deficiency*; D011164:Porphyrias / Q000188:drug therapy*
D000623:Porphobilinogen Synthase