As the red cells URO-S activity is employed for diagnosing acute intermittent porphyria (AIP) and as it is known that sulphonamides provoke attacks of AIP, we considered interesting to study the effect of administering sulphamerazine (SMZ) at varying doses and after different intervals, on in vitro blood URO-S activity and on in vitro brain porphyrin biosynthesis in rats. The maximal inhibition on URO-S activity (30%) measured at 45°C was observed when rats were injected with SMZ (i.p., 1 g/kg b.wt, 4 ml/kg) and killed after 8 h of drug administration. Using different SMZ doses (i.p., 0.5 g/kg and 2 x (1 g/kg)) or by oral administration of the drug (1 g/kg, 4 ml/kg) no change in this inhibition degree was found. SMZ administration did not alter uroporphyrin III biosynthesis when measured at 37°C, therefore we could asign to the cosynthase a sort of protective role in the complex leading to the synthesis of this physiological intermediate. When rats were killed after 4 h of receiving SMZ (i.p., 1 g/kg, 4 ml/kg) an increase of 135% in brain porphyrin biosynthesis in 24 h incubations was found. At longer times of treatment (8 and 18 h), a dual effect was observed (20% inhibition for 4-6 h incubations and 24 % activation for 24 h incubations). Both inhibitory and activating effects were also detected when the SMZ dose was doubled. These results could be attributed to changes in the kinetic behaviour of more than one enzyme in the heme pathway.
Documento: | Artículo |
Título: | The action of sulphamerazine on porphyrin biosynthesis in rats |
Autor: | Kotler, M.L.; Juknat, A.A.; Correa Garcia, S.R.; Del Batlle, C.A.M. |
Filiación: | Centro de Investigaciones sobre Porfirinas y Porfirias, Ciudad Universitaria, 1428 Buenos Aires, Argentina |
Palabras clave: | porphyrin; sulfamerazine; intraperitoneal drug administration; nonhuman; porphyria; priority journal; rat |
Año: | 1988 |
Volumen: | 16 |
Número: | 7 |
Página de inicio: | 323 |
Página de fin: | 324 |
Título revista: | Medical Science Research |
Título revista abreviado: | MED. SCI. RES. |
ISSN: | 02698951 |
CODEN: | MSCRE |
CAS: | porphyrin, 24869-67-8; sulfamerazine, 127-58-2, 127-79-7 |
Registro: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02698951_v16_n7_p323_Kotler |