Hypothyroidism Induced by Propyl-thio-uracil or Methimazole Inhibit d-Aminolevulinate Dehydratase in Rat Blood
Fernanda Sbaraini Gravina, Clarice Kras Borges da Silveira, Adriano Martimbianco de Assis, Carolina Guerini Souza, Lisiane G. Londero, Marcos Luiz Santos Perry, Ana Maria Oliveira Battastini
Departamento de Bioquímica, ICBS -Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brasil.
It has long been know that in vertebrates hypothyroidism leads to a desacceleration of the basal metabolic rate. In hypothyroidism pathology there is a decrease on intravascular volume, which can reflect on hematocrit. Delta-aminolevulinate dehydratase (d-ALA-D), an enzyme in the heme biosynthesis pathway, is essencial for all aerobic organisms. It is a marker for oxidative stress because its active sulfhydryl group renders it highly sensitive to pro-oxidant elements which impair its function. The present work investigated the d-ALA-D activity on hypothyroids rats blood. Hypothyroidism was induced by administering propyl-thio-uracil (PTU) (0,05% w/v) or methimazole (MMI) (0,02% w/v) to drinking water for 21 days during the lactation. d-ALA-D activity was assayed by the method of Sassa (1982) by measuring the rate of product (porphobilinogen) formation, using potassium phosphate buffer pH 6,4. The reaction product was determined using modified Ehrlich´s reagent at 555nm, with a molar absorption coefficient of 6,1x104 M-1 for the Ehrlich-porphobilinogen salt. We used DL-dithiothreitol (DTT), a sulfhydryl reducing agent, which mantains d-ALA-D activity in vitro when the enzyme is challenged with oxidizing agents. Both treatments (PTU or MMI) decreased the d-ALA-D activity. The treatment with PTU afforded higher decrease of d-ALA-D activity than the treatment with MMI. DDT caused an increase in enzyme activity, but it was not efficient in counteraracting the inhibitory effect of hypothyroidism induced by PTU, this indicates that sulfydryl group oxidation is not involved in the inhibition. However in the induce with MMI, DTT afforded protection and the enzyme activity was recovered, like in control group. The recovery can indicate that sulfydryl group was oxidated. Other studies are necessery to clarify the mechanism of inhibition, with the use of other antioxidants besides of DTT.
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