Experimental hypothyroidism inhibits delta-aminolevulinate dehydratase activity in neonatal rat blood and liver.

Abstract

The aim of this study was to investigate the potential relationship between hypothyroidism and delta-aminolevulinate dehydratase (delta-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 [T(3)]) included weanling rats whose mothers were exposed to PTU similarly to those in the hypothyroid group, but pups received daily subcutaneous injections of T(3) (20 microg/kg, from Postnatal Days 2-20). After the treatment, serum T(3) levels were drastically decreased (around 70%) in the PTU group, and this phenomenon was almost reverted by exogenous T(3). PTU decreased blood delta-ALA-D activity by 75%, and T(3) 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 T(3) was coadministered. Dithiothreitol did not change blood delta-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 delta-ALA-D inhibition. PTU did not affect blood delta-ALA-D activity in vitro. These results are the first to show a correlation between hypothyroidism and decreased delta-ALA-D activity and point to this enzyme as a potential molecule involved with hypothyroidism-related hematological changes.

• Authors: 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, Marcos L S Perry
• Journal: Experimental biology and medicine (Maywood, N.J.) (Exp Biol Med (Maywood)) Vol. 232 Issue 8 Pg. 1021-6 (Sep 2007) ISSN: 1535-3702 [Print] England
• PMID: 17720948 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antithyroid Agents
• Hemoglobins
• Triiodothyronine
• Thiouracil
• Porphobilinogen Synthase
• Dithiothreitol

Topics

• Animals
• Animals, Newborn
• Antithyroid Agents (toxicity)
• Congenital Hypothyroidism (blood, chemically induced, enzymology)
• Disease Models, Animal
• Dithiothreitol (pharmacology)
• Enzyme Activation (drug effects)
• Erythrocytes (enzymology)
• Female
• Hemoglobins (analysis)
• Lactation (blood)
• Liver (enzymology)
• Male
• Porphobilinogen Synthase (blood)
• Rats
• Rats, Wistar
• Thiouracil (toxicity)
• Triiodothyronine (pharmacology)