Experimental hypothyroidism inhibits delta-aminolevulinate dehydratase activity in neonatal rat blood and liver.
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.
Gravina
Fernanda S
FS
Departamento de Bioquímica, Rua Ramiro Barcelos 2600 Anexo, Universidade Federal do Rio Grande do Sul, 90035-003, Porto Alegre, RS, Brazil.
da Silveira
Clarice K B
CK
de Assis
Adriano M
AM
Rieger
Débora K
DK
Guerini
Carolina
C
Müller
Alexandre P
AP
Farina
Marcelo
M
Rotta
Liane N
LN
Perry
Marcos L S
ML
D000818:Animals; D000831:Animals, Newborn; D013956:Antithyroid Agents / Q000633:toxicity; D003409:Congenital Hypothyroidism / Q000097:blood / Q000139:chemically induced / Q000201:enzymology*; D004195:Disease Models, Animal; D004229:Dithiothreitol / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004912:Erythrocytes / Q000201:enzymology; D005260:Female; D006454:Hemoglobins / Q000032:analysis; D007774:Lactation / Q000097:blood; D008099:Liver / Q000201:enzymology*; D008297:Male; D000623:Porphobilinogen Synthase / Q000097:blood*; D051381:Rats; D017208:Rats, Wistar; D013889:Thiouracil / Q000633:toxicity; D014284:Triiodothyronine / Q000494:pharmacology
D013956:Antithyroid Agents; D006454:Hemoglobins; D014284:Triiodothyronine; D013889:Thiouracil; D000623:Porphobilinogen Synthase; D004229:Dithiothreitol