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ORIGINAL RESEARCH ARTICLE

Experimental Hypothyroidism Inhibits -Aminolevulinate Dehydratase Activity in Neonatal Rat Blood and Liver

Fernanda S. Gravina^*, Clarice K. B. da Silveira^*, Adriano M. de Assis^*, Débora K. Rieger^*, Carolina Guerini^*, Alexandre P. Müller^*, Marcelo Farina, Liane N. Rotta and Marcos L. S. Perry^*,1

^* Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, Santa Caterina, Brazil; and Fundação Faculdade Federal de Ciências Médicas de Porto Alegre and Universidade Luterana do Brasil, Canoas, Rio Grande do Sul, Brazil

To whom requests for reprints should be addressed at ¹ Departamento de Bioquímica, Rua Ramiro Barcelos 2600 Anexo, Universidade Federal do Rio Grande do Sul, 90035–003, Porto Alegre, RS, Brazil. E-mail: mlsperry{at}excite.com

The aim of this study was to investigate the potential relationship between hypothyroidism and -aminolevulinate dehydratase (-ALA-D) activity in rat blood and liver. Experimental hypothyroidism was induced in weanling rats by exposing their mothers to propylthiouracil (PTU) diluted in tap water (0.05% w/ v), ad libitum, during the lactational period (PTU group). Control (euthyroid) group included weanling rats whose mothers received just tap water, ad libitum, during the lactational period. Reverted-hypothyroid group (PTU + 3,3',5-triiodo-L-thyronine [T₃]) included weanling rats whose mothers were exposed to PTU similarly to those in the hypothyroid group, but pups received daily subcutaneous injections of T₃ (20 µg/kg, from Postnatal Days 2–20). After the treatment, serum T₃ levels were drastically decreased (around 70%) in the PTU group, and this phenomenon was almost reverted by exogenous T₃. PTU decreased blood -ALA-D activity by 75%, and T₃ treatment prevented such phenomena. Erythrocytes and hemoglobin levels were increased by 10% in PTU-treated animals and higher increments (around 25%) were observed in these parameters when exogenous T₃ was coadministered. Dithiothreitol did not change blood -ALA-D activity of PTU-exposed animals when present in the reaction medium, suggesting no involvement of the enzyme’s essential thiol groups in PTU-induced -ALA-D inhibition. PTU did not affect blood -ALA-D activity in vitro. These results are the first to show a correlation between hypothyroidism and decreased -ALA-D activity and point to this enzyme as a potential molecule involved with hypothyroidism-related hematological changes.

Key Words: hypothyroidism • anemia • thyroid hormones • propylthiouracil • -aminolevulinate dehydratase

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