Experimental latent and acute porphyria in the non-fasted rat; preventive effect of propranolol.
This study demonstrates an experimental model of the biochemical pattern of the 'latent phase' of hepatic porphyria subject to 'acute attack', upon application of prophyrinogenic stimuli. The 'latent phase' was achieved by administering 3,5-diethoxycarbonyl-1, 4-dihydrocollidine [DDC], 70 mg kg-1 day, orally to non-fasted rats. A two- and threefold increase in coproporphyrin in urine and protoporphyrin in faeces, respectively, were observed. An 'acute attack' was induced by phenobarbitone (PB), 100 mg kg-1, administered on the third day of treatment with DDC, followed by administration of 2-allyl-2-isopropylacetamide (AIA), 470 mg kg-1, on the fourth day. A fourfold elevation in urinary porphobilinogen (PBG) and delta-aminolevulinic acid (ALA) and further increase of three- and fourfold in urinary coproporphyrin and faecal protoporphyrin, respectively, was observed. The effect of DDC, AIA and PB on the excretion of PBG and porphyrins was found to be synergistic rather than additive. dl-Propranolol, 700 mg kg-1, given to DDC treated rats 'latent phase' reduced the amount of porphyrins excreted in urine and faeces to those observed in control dimethyl sulphoxide (DMSO) treated rats. It also prevented induction of 'acute attack' caused by the combination of PB and AIA. It is shown that dl-propranolol affects a few parameters in the haem biosynthetic pathway. Its beneficial effect in porphyria is probably the result of increasing the concentration of haem in the free haem pool.
Schoenfeld
N
N
Laboratory of Biochemical Pharmacology, Beilinson Medical Center, Petah Tiqva, Israel.
Mamet
R
R
Mevasser
R
R
Atsmon
A
A
D000208:Acute Disease; D000502:Allylisopropylacetamide; D000622:Aminolevulinic Acid / Q000652:urine; D000818:Animals; D003306:Coproporphyrins / Q000652:urine; D003997:Dicarbethoxydihydrocollidine; D005243:Feces / Q000737:chemistry; D008297:Male; D010634:Phenobarbital; D011162:Porphobilinogen / Q000652:urine; D011164:Porphyrias / Q000139:chemically induced / Q000517:prevention & control*; D011433:Propranolol / Q000627:therapeutic use*; D011524:Protoporphyrins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D003306:Coproporphyrins; D011524:Protoporphyrins; D000502:Allylisopropylacetamide; D003997:Dicarbethoxydihydrocollidine; D011162:Porphobilinogen; D000622:Aminolevulinic Acid; D011433:Propranolol; D010634:Phenobarbital