Alternative complement pathway and factor B activities in rats with altered blood levels of thyroid hormone

Evaluating the activity of the complement system under conditions of altered thyroid hormone levels might help elucidate the role of complement in triggering autoimmune processes. Here, we investigated alternative pathway (AP) activity in male Wistar rats (180 ± 10 g) after altering their thyroid hormone levels by treatment with triiodothyronine (T3), propylthiouracil (PTU) or thyroidectomy. T3 and thyroxine (T4) levels were determined by chemiluminescence assays. Hemolytic assays were performed to evaluate the lytic activity of the AP. Factor B activity was evaluated using factor B-deficient serum. An anti-human factor B antibody was used to measure factor B levels in serum by radial immunodiffusion. T3 measurements in thyroidectomized animals or animals treated with PTU demonstrated a significant reduction in hormone levels compared to control. The results showed a reduction in AP lytic activity in rats treated with increasing amounts of T3 (1, 10, or 50 µg). Factor B activity was also decreased in the sera of hyperthyroid rats treated with 1 to 50 µg T3. Additionally, treating rats with 25 µg T3 significantly increased factor B levels in their sera (P < 0.01). In contrast, increased factor B concentration and activity (32 percent) were observed in hypothyroid rats. We conclude that alterations in thyroid hormone levels affect the activity of the AP and factor B, which may in turn affect the roles of AP and factor B in antibody production.

Validación del ensayo de disolución de las tabletas de propiltiuracilo 50 mg / Validation of the dissolution assay of propylthiouracil 50 mg

Se validó un método para evaluar la disolución de las tabletas de propiltiuracilo 50 mg por espectrofotometría, con detección ultravioleta a 274 nm. Se evaluaron los parámetros de especificidad, linealidad, precisión e influencia de la filtración. La curva de linealidad se realizó en el rango de 3,32 a 7,75 µg/mL con un coeficiente de correlación igual a 0,99984; la prueba estadística para el intercepto y la pendiente se consideró no significativa. En el estudio de la influencia de la filtración se demostró que en la filtración no se adsorbe el principio activo ni se aportan interferencias al filtrado, por lo que es posible su empleo.

A method to evaluate the dissolution of propylthiouracil tablets 50 mg by spectrophotometry, with ultraviolet detection of 274 nm, was validated. Specificity, linearity, precision and filtration influence were the evaluated parameters. The linearity curve was made at the range from 3.32 to 7.75 µg/mL with a correlation coefficient equal to 0.99984. The statistical test for the interval and the slope was not significant. In the study of filtration influence it was proved that the active principle was not absorbed in the filtration and that there were no interferences in the filtration, which made its use possible.

Influência do hipotireoidismo induzido por propiltiouracil na mucosa gengival do rato / Influence of propilthiouracil-induced hypothyroidism on rat gingival mucosa / Influence of propilthiouracil-induced hypothyroidism on rat gingival mucosa

O objetivo foi verificar a influência da deficiência dos hormônios tireoideanos induzida por propiltiouracil (PTU) na mucosa gengival do rato, analisando bioquimicamente as proteínas totais, colágeno (hidroxiprolina) e população celular (DNA). Foram utilizados 50 ratos machos da cepa Sprague-Dawley, separados em 2 grupos: propiltiouracil (PTU) (10 mg/d i.p.), e controle (C), durante 10 semanas. As proteínas totais foram determinadas pelo método de Lowry, a hidroxiprolina pelo método de Newman e DNA pelo método de Burton. Observou-se diminuição das proteínas totais no grupo PTU (PTU= 41,23 ± 24,05; C= 63,36 ± 18,05); não houve diferença na hidroxiprolina e DNA (PTU= 2,18 ± 1,48; C= 2,29 ± 1,51) e (PTU= 0,33 ± 0,19; C= 0,46 ± 0,31). Conclui-se que o tratamento com PTU diminui o conteúdo de proteínas totais na mucosa gengival do rato, provavelmente pela diminuição da síntese protéica, sem alteração do colágeno e da população celular.

This work aimed at verifying the influence of propilthiouracil (PTU)-induced thyroid hormone deficiency on gingival mucosa of young male rats, measuring total protein concentration, collagen content and DNA concentration as indices of cellular population. Fifty Sprague-Dawley rats were used. The animals were grouped in: PTU-treated (i.p. 10 mg/d) and control rats (C). The experience was maintained for a period of 10 weeks. Total protein content of gingival mucosa tissue was determined by the Lowry method; hydroxyprolin rate, as prototype aminoacid of collagen, was determined using the Newman method, and DNA concentration was measured by Burton's methodology. The results showed decreased amounts of PTU-treated rats gingival total protein content (PTU= 41.23 ± 24.05 vs. C= 63.36 ± 18.05); no alterations were seen in hydroxyprolin concentration neither in DNA content of PTU treated rats, respectively (PTU= 2.18 ± 1.48 vs. C= 2.29 ± 1.51) and (PTU= 0.33 ± 0.19 vs. C= 0.46 ± 0.41). Thus, PTU treatment promotes a decrease in total protein content of rat gingival mucosa that may be interpreted as a decrease in protein synthesis induced by the hypothyroid condition, but with no alteration either in collagen or nucleic acid rates.

Effect of abouthiouline, a novel drug with therapeutic potential as antithyroid, on some biochemical and hematologic parameters in mice and rats

Abouthiouline [1-Cyclohexyl-3[3-quinolyl]-2-thiourea] is a novel compound with antithyroid activity. Abouthiouline [ABL] was designed based on structure-activity relationships [E-state indexes] aimed at reducing the antioxidant properties of the compound by modification of acyclic thiourylene moiety. Antioxidant effects of currently available treatments such as propylthiouracil [PTU], methimazole [MTM] are associated with an incidence of agranulocytosis and aplastic anemia. In the present study, the preclinical toxicology of ABL was determined in mice and rats and compared with two reference compounds, namely, propylthiouracil, methimazole. Following short-term administration [7 days] to mice, ABL had minimal effects on biochemical parameters, although significant reductions in both total protein and albumin were noted. Long-term studies [30 days] in rats revealed significant effects of Abouthiouline, propylthiouracil and methimazole on serum electrolyte and glucose levels. Abouthiouline had no detrimental effects on hematologic parameters. However, total WBC count [propylthiouracil] and neutrophil levels [propylthiouracil and methimazole] were significantly decreased among other treatment groups. The results of this investigation suggest that Abouthiouline is a promising new antithyroid therapy with a reduced risk of hematologic toxicity that is associated with PTU and MTM. Further studies are warranted to assess the safety and efficacy of Abouthiouline

Polyunsaturated fatty acids (PUFA) regulate neurotransmitter contents in rat brain.

The effects of feeding of 6-propylthiouracil (6-PTU) and polyunsaturated fatty acids (PUFA) independently and in combination and administration (ip) of a single dose of triiodothyronine (T3) (2.5 microg/100 g body wt) along with feeding of 6-PTU and PUFA were studied in rat brain. Dopamine (DA), 5-hydroxytryptophan (5-HTP), serotonin (5-HT), 5-hydroxy indole acetic acid (5-HIAA), norepinephrine (NE) and epinephrine (EPI) contents were assayed in the hypothalamus and cerebral cortex regions. It was found that 6-PTU feeding resulted in decrease in dopamine, 5-HT, 5-HTP and 5-HIAA in both regions. In animals fed with PUFA followed by administration of T3, the DA level was found normal.

Role of thyroidal and testicular hormones in regulation of tissue respiration in male air-breathing fish, Clarias batrachus (Linn.).

In vivo and in vitro effects of thyroidal hormones (MIT, DIT, T3, T4), propyl thiouracil (PTU), testosterone and cyproterone acetate were studied on the rate of tissue (liver, muscle, kidney and brain) respiration of adult male C. batrachus during winter and summer/rainy seasons. Monoiodotyrosine (MIT) and diiodothyrosine (DIT) increased the respiratory rate in a dose-dependent and temperature-independent manner. Triiodothyronine (T3) and thyroxine (T4) stimulated tissue respiration during summer/rainy months but not during winter. PTU decreased tissue respiration during summer/rainy season and also at simulated low temperature. Testosterone invariably stimulated the rate of respiration of the tissues, while in vivo treatment with cyproterone acetate significantly decreased the metabolic rate of all the tissues. The findings suggest that in C. batrachus MIT and DIT may be more important than T3 and T4 at low temperature, endogenous thyroid hormones are involved indirectly in energy metabolism even during winter/at low temperature and testicular hormones are actively involved in the respiration.

Effect of congenital hypothyroidism on cell density in the ganglion cell layer of the rat retina

The effect of congenital hypothyroidism on the visual system of Wistar rats was studied by determining neuron density in the retinal ganglion cell layer. Retinae of adult rats from mothers treated with propylthiouracil, 50 mg/day, starting on the l5th day of pregnancy (PTU group), and of adult rats from untreated mothers (control group) were examined. Retinae were prepared, and the neurons in the nasotemporal region located above the optic disc were counted. Hypothyroid rats showed a significant reduction in the retinal area (about 6.8 per cent), when compared to controls. The cell density in the retinal ganglion cell layer was significantly decreased in 6 PTUtreated compared to 5 control retinae in total (2,793 ñ 330 vs 3,704 ñ 662 neurons/mm2), nasal (3,031 ñ 580 vs 3,853 ñ 699 neurons/mm2) and temporal (2,555 ñ 156 vs 3,555 ñ 827 neurons/mm2) regions. These alterations in a region considered to be one of the most specialized in the visual process suggest a structural deficiency induced by congenital hypothyroidism, with a possible decrease in the vísual acuity of the rat.

Facilitatory role of serotonin (5-HT) in the control of thyrotropin releasing hormone/thyrotropin (TRH/TSH) secretion in rats

In order to investigate the role of serotonin in the regulation of thyrotropin (TSH) secretion, control and propylthiouracil (PTU)treated male Wistar rats weighing approximately 250 g were subjected to ip injections of methysergide (MET, 10 mug/l00 g body weight), a serotonergic receptor blocker, and killed 60 min later by decapitation. Serum and pituitary concentrations of TSH were measured by radioimmunoassay. In addition, the pituitary release of TSH was estimated in an in vitro system in which pituitary glands were incubated with hypothalamic extracts. MET treatment led to a decrease in pituitary (94.12 ñ 18.55 vs 199.30 ñ 31.47 mug/mg, N = 20), and serum (l.95 ñ 0.92 vs 4.26 ñ 1.40 ng/ml, N = 20) TSH concentration (P

Effect of pre- and postnatal propylthiouracil administration on the propagation of cortical spreading depression of adult rats

The effect of treatment with propylthiouracil early in life (PTU; 8 mg k-1 day-1, ip, from day 17 of gestation to postnatal day 42) on the susceptibility of the cerebral cortex to spreading depression (SD) was studied in 13 adult Wistar rats (90-100 days of age). Ten animals injected with Ringer solution served as control. Adult PTU-treated rats displayed a significant (P < 0.05) reduction in body weight (mean +/- SD: 139.9 +/- 28.9 g vs 304.9 +/- 42.8 g) as well as wet brain weight (1.39 +/- 0.12 g vs 1.86 +/- 0.13 g) and dry brain weight (247.3 +/- 24.2 mg vs 359.4 +/- 30.1 mg). Their thyroid glands presented histological changes indicative of hypofunction and SD velocity of propagation was significantly reduced all along the 6 h of the recording session (mean +/- SD ranges: 1.90 +/- 0.46 to 2.52 +/- 0.68 mm/min vs 3.49 +/- 0.57 to 3.71 +/- 0.55 mm/min). The results indicate that PTU early in life was effective in producing hypothyroidism and that in this situation cortical susceptibility to SD is impaired

Estudo histológico comparativo da tireóide de ratos tratados, isoladamente ou em grupo, com propil-tiouracil / Effects of propylthyouracil on the thyroid gland of rats treated either, isolately or in groups. Histological study

Foram estudadas, histologicamente, as tireóides de ratas tratadas em grupo e isoladamente com 6-propil-2-tiouracil adicionado à raçäo diária. Foi constatado que, comparativamente, as glândulas tireóides dos animais distribuídos isoladamente em gaiolas individuais, mostram características que indicam a manifestaçäo de um quadro de hipotireoidismo intensificado o que leva recomendar a distribuiçäo dos animais individualmente para obtençäo do hipotireoidismo experimental quando se utiliza, como droga de eleiçäo, o 6-propil-2-tiouracil ministrado à raçäo

Contribuiçäo ao estudo do mecanismo da pertubaçäo da homeostase glicêmica no hipertiroidismo

Objetivando investigar a natureza da influência do hipertiroidismo no metabolismo dos carboidratos e aparecimento ou agravamento do diabete que pode ocorrer, estudamos dez pacientes tirotóxicos portadores de doença de Graves antes e após o tratamento, inicialmente com propranolol e, depois, com propiltiouracil. O uso do propranolol näo interferiu com a tolerância à glicose secreçäo de insulina ou receptores para insulina em eritrócitos. O tratamento com propiltiouracil reduziu a insulinemia basal e aumentou a ligaçäo específica máxima da insulina a eritrócitos (p < 0,005). Concluímos que o hipertiroidismo induz a resistência à insulina por diminuir a ligaçäo da insulina a seus recptores específicos nos tecidos. Essa resistência à insulina exige maior secreçäo do hormônio e pode causar intolerância à glicose em indivíduos suscetíveis. Isto é, portadores de reserva pancreática diminuída em funçäo da idade ou de herança diabética

Histological study of the thyroids of rats treated with propyl thyouracil, parotidectomyzed and parotidectomyzed treated with propyl thyouracil

Os autores estudaram, histologicamente, as glândulas tireóides de quatro grupos experimentais de ratos: Grupo controle (I), ratos submetidos à extirpaçäo cirúrgica das glândulas parótidas (Grupo II), ratos tratados com 25 mg diários de 6-propil-2-tiouracil (Grupo III) e ratos parotidectomizados e posteriormente tratados com 25 mg diários de 6-propil-2-tiouracil (Grupo IV). Após 26 dias consecutivos de administraçäo de 6-propil-2-tiouracil, todos os animais foram sacrificados. O aspecto histológico da tireóide dos animais tratados com a droga antitireoideana (Grupo III) foi compatível com o de hipofunçäo da glândula. Nos animais parotidectomizados (Grupo II), o aspecto histológico foi o de hiperfunçäo glandular. Nos animais parotidectomizados e tratados com o 6-propil-2-tiouracil (Grupo IV), o aspecto histológico mostrou características intermediárias entre o dos Grupos II e III. Estes resultados sugerem que a parotidectomia atenua a hipofunçäo tireoideana causada pela administraçäo do 6-propil-2-tiouracil, bem como vem enfatizar a hipótese da inter-relaçäo funcional entre glândulas salivares e tireóide