Effects of low concentrations of a polychlorinated biphenyl, Aroclor 1254 on membrane bound ion dependent ATPases in mice liver.

Aroclor 1254, a polychlorinated biphenyl, is present in the environment in low concentration but references on its toxic effects on liver cell membrane proteins and the mechanism of actions are not abundantly available. Therefore, the present study was undertaken to investigate the low level, sub-acute dose and exposure duration dependent effects of Aroclor 1254 on total, Na+, K+, Ca2+ and Mg2+-ATPases of the mouse liver. The hypotheses tested in the present study were, (a) whether the low, environmentally available dose and the exposure durations of Aroclor 1254 affects the membrane-bound ion dependent ATPases, and (b) if a response was observed, whether it is a direct or indirect effects of the toxicant. Groups of mice were exposed to different doses (0.1 and 1mg kg-1 body weight d-1) and exposure durations (4 d, 8 d and 12 d) of Aroclor 1254. The results indicated significant exposure duration dependent changes in the specific activity of the selected membrane bound ATPases. As the observed changes were mostly enzyme stimulation after toxication through oral administration, the effects of the Aroclor were possibly indirect, through complex chain of reactions.

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.

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 radish (Raphanus sativus Linn.) on thyroid status under conditions of varying iodine intake in rats.

Cruciferous plants viz. cabbage, cauliflower, turnip, radish, mustard etc. that contain goitrogenic/antithyroid substances, constitute a portion of regular human diet. The effect of chronic feeding of fresh and cooked radish, R. sativus under varying state of iodine intake on morphological and functional status of thyroid in albino rats was evaluated by thyroid gland morphology and histology, thyroid peroxidase activity, serum triiodothyronine, thyroxine and thyrotropin levels. The consumption pattern of iodine and goitrogens of cyanogenic origin was evaluated by measuring urinary iodine and thiocyanate levels respectively. After chronic radish feeding, increased weight of thyroid gland, decreased thyroid peroxidase activity, reduced thyroid hormone profiles and elevated level of thyrotropin were observed resembling a relative state of hypoactive thyroid gland in comparison to control even after supplementation of adequate iodine.

Hipertiroidismo y su tratamiento / Hyperthyroidism and its treatment

El hipertiroidismo afecta el 0,5 a 1,0 por ciento de la población general, siendo 10 veces más frecuente en la mujer que en el hombre. El 85 por ciento de los casos corresponde a enfermedad de Basedow-Graves de naturaleza autoinmune. El 15 por ciento restante se debe a bocio multinodular y adenoma tóxico, tiroiditis de Quervain, etc. Hay casos iatrogénicos tales como los debido a administración de amiodarona. El cuadro clínico es una combinación de manifestaciones de tirotoxicosis, bocio y oculopatía y de compromiso muscular y cardíaco. El tratamiento consiste en administración de drogas antitiroídeas (propiltiouracilo); yodo radioactivo y/o resección quirúrgica según los casos

Manejo actual del hipertiroidismo / Current treatment of hypertiroidism

El hipertiroidismo es una enfermedad común, que afecta tanto a hombres como a mujeres, tiene expresiones clínicas semejantes; sin embargo, las causas son diferentes y por ello hay diversas maneras de tratarlo. A continuación se hace una revisión de los diferentes esquemas de tratamiento farmacológico (medicamentos antitiroideos, iodo inorgánico, iodo radiactivo) y quirúrgico

Development of new antithyroid compounds with reduced antioxidant property

Based on literature evaluation, we hypothesize that in order to control graves disease and the onset of drug induced agranulocytosis the trends in antithyroid therapy should be modified to include acyclic thiourea with reduced anioxidant property. A linear relationship was developed between percentage of inhibition of luminol enhanced chemiluminescence [%CL] of stimulated polymorphonuclear leucocytes [PMNLs] obtained from Imamura et al. [Acta Endocrinological, 1986; 112:210-216.] data of currently used antithyroids and related compounds and their atom level electrotopological state [E-state] indexes of their thiourylene moiety [S[N AND S]]. The resulted relationship [% CL inhibition = 349.254 [ +/- 8.52] -37.692 [ +/- 1.13] [S[N AND S]; = 0.999; SEM = 0.47; F= 1108.1; P = 0.019] was utilized as a guideline for the rational selection of thiourylene type compounds [with S[N and S] >8] with reduced antioxidant property. The compounds selected were evaluated for their antioixdant property utilizing their influence on luminol-enhanced chemiluminescence [CL] of phorbol myristate acetate [PMA] induced human PMNLs and was found to agree with the guideline extracted from Imamura et al data. The formation of the selected compounds of their charge transfer complex with iodine was determined spectroscopically and utilized as a primary criteria for their potential antithyroid activity. In addition, these agents were screened for antithyroid activity in rats using [125] I-thiocyanate discharge technique. The relative efficacy [in relation to equimolar dose of propylthiouracil] of the tested agents with respect to both [125] I-uptake and the rate of [125] I-discharge were determined and proved that at least one of the three investigated compounds [abouthiouline] has higher antithyroidal activity than propylthiouracil with respect to the rate of [125] I-discharge. The relative efficacy of abouthiouline [1-cyclohexy1-3[3-quinoly1]-2-thiourea], after equimolar dose was 131.13% and 51.72% of that of propylthiouracil with respect to the rate of [125] I-discharge and [125] I-uptake respectively. The importance of the thyroid [125] I-discharge in antithyroid therapy in reducing the dose and the duration of treatment is discussed. Since the ratio of the percent efficacy with respect to the rate of [125] I-discharge to [125] I-uptake of abouthiouline is 2.54, it is perceived that abouthiouline is of potential value as antithyroid agent after adjusting the dose with respect to the therapeutic dose of propylthiouracil. In conclusion, abouthiouline has lower toxicity [LD[50] >800 mg/kg] reduced antioxidant property as well as higher antithyroidal efficacy than propylthiouracil with respect to the rate of 125I discharge. In view of the toxic omplications of the antioxidant property of the currently used antithyroid agents it is suggested that abouthiouline will be beneficial in reducing the severity of the immune reaction of both the Graves disease and the drug induced agranulocytosis. Further supportive investigations are in progress