Effect of different doses of ascorbic acid on thyroid activity in rats at different levels of dietary protein intake.

Rats, which can synthesize vitamin C, react similarly to graded doses of ascorbic acid as guinea pigs. Low doses of ascorbic acid stimulate and high doses inhibit the thyroid activity of rats which are supplied with normal and high percentages of protein. The stimulatory effect of low doses of ascorbic acid on hyperactive thyroid of high protein fed animals is additive. Ascorbic acid has no significant effect on the thyroid of low protein fed animals (deficient diet supplied for 21 days). In the initial stages of protein deficiency (deficient diet supplied for 11 days) the effectiveness of vitamin C on thyroid of rats was still significant. Deiodinase enzyme activity of peripheral tissues is markedly reduced in animals supplied with 2% of protein for 21 days, but this effect is less intense in animals supplied with 2% of protein for 11 days.     

硒缺乏与甲状腺激素代谢及功能

Ｉ型脱碘酶为含硒酶,缺硒时,该酶活性下降,使循环Ｔ４增高,外周组织Ｔ３水平下降。缺硒可加速甲状腺组织碘的耗竭,并加重某些缺碘的生物学效应,缺硒还可能与碘缺乏病的发生发展有关。以缺硒为主要病因的克山病存在甲状腺激素代谢异常,其心肌呼吸酶活性变化与缺碘引起的甲状腺功能低下相似,缺碘可缺硒引起的甲状腺激素代谢改变与克山病的发生可能有关。     

Transfer of iodine through the milk in protein-restricted lactating rats

Iodine supply is important to avoid neonatal hypothyroidism. This study evaluated whether protein restriction during lactation affects iodine transfer to the pups through the milk. We studied lactating rats fed an 8% protein-restricted diet (PR), a control 23% protein diet (C), and an energy-restricted diet group (ER). On days 4, 12 and 21, mothers were separated from their pups for 4 h, injected with (131)I IP, and put together with their pups. The animals were killed 2 h later. PR pups had a significant decrease in iodine uptake in the gastric content and duodenal mucosa on the 4th day. On the contrary, at 12 and 21 days radioiodine was increased in the gastric content and in the duodenal mucosa. ER pups had an increase in iodine uptake in the gastric content and in the duodenal mucosa only at the end of lactation. The thyroid iodine uptake in PR pups was significantly decreased on the 4th day and significantly increased on the 21st day compared to control. When injected IP with an equivalent amount of (131)I, the PR pups had a decrease in thyroid iodine uptake on the 4th and 12th day, while ER pups had no significant changes. So, these data suggest that protein restriction during lactation was associated with lower iodine secretion into the milk in the beginning of lactation. However, at the end of lactation, an adaptation process seems to occur leading to a higher transfer of iodine through the milk that compensates the impairment of thyroid iodine uptake in these pups.     

Functional activity of the thyroid gland and distribution of its hormones in peripheral tissues under experimental liver disease

Experimental acute toxic hepatitis causes functional reconstruction of the thyroid gland accompanied by intensified levels of total iodine and its hormonal compounds in blood. In most of non-thyroid tissues a decrease in the total and hormonal iodine content is revealed, but in kidneys these indices are considerably higher. The level of the nonhormonal iodine compounds in blood and tissues under study does not essentially vary and only in the liver, heart and lungs the expressed lowering of inorganic iodides is observed.     

Vitamin A deficiency reduces uptake of beta-carotene by brush border membrane vesicles but does not alter intestinal retinyl ester hydrolase activity in the rat

Vitamin A deficiency has been reported to result in mild structural and functional changes within the small intestine. The objective of this study was to measure the impact of vitamin A deficiency in the rat on several functional aspects of beta-carotene uptake and intestinal retinyl ester hydrolysis. These included uptake of (14)C-beta-carotene by brush border membrane vesicles (BBMV) and in vitro activity of intrinsic retinyl ester hydrolase (REH). Rats (n = 33) were randomly assigned to receive one of three dietary treatments: vitamin A deficient (-VA), vitamin A sufficient pair-fed (PF), or vitamin A sufficient free access-fed (FA). Liver, serum retinol, and growth data were used to verify clinical vitamin A deficiency. Rats in the -VA group were clinically vitamin A deficient by Day 56 on a vitamin A-free diet and, at that point, all rats were randomly assigned to one of two experimental treatments: BBMV studies or REH activity assays. Uptake of (14)C-beta-carotene by BBMV was significantly suppressed (P < 0.05) in -VA rats when compared to both PF and FA control rats during early passive uptake equilibration (10-20 sec). Uptake was also significantly decreased by BBMV isolated from -VA rats compared to PF controls, but not FA controls, after a 10-min incubation (P < 0.05). In vitro activity of REH was not impacted by vitamin A deficiency in rats, although a trend for greater activity from -VA rats was noted. These data suggest that vitamin A deficiency impairs enterocyte membrane uptake of beta-carotene without altering the enzymatic activity of intrinsic REH.     

Rapid induction of vitamin A deficiency in rabbits

Clinical and biochemical evidence of vitamin A deficiency was produced in rabbits as early as 4-5 weeks after weaning to a vitamin A deficient diet from dams maintained during lactation on the deficient diet. Mean serum retinol levels at the time of weaning for the deficient dams were 25 +/- 6 micrograms/dl compared with 74 +/- 8 micrograms/dl for the controls. Five weeks after weaning, 25% of pups fed the vitamin A deficient diet had ocular lesions characterized by the accumulation of sloughed epithelium on the cornea. At this time, mean serum values of the pups were 10 +/- 4 micrograms/dl for the deficient group and 73 +/- 8 micrograms/dl for the controls. Evidence of critically depleted liver stores was documented in the deficient rabbits by an elevated relative dose response test (54 +/- 18%) that did not occur in the control group (6 +/- 5%). Although food consumption was similar, weight gain was lower in the deficient group when compared to the control group.     

Iodide excess exerts oxidative stress in some target tissues of the thyroid hormones

Environmental iodine deficiency continues to be a significant public health problem worldwide. On the other hand, iodide excess results principally from the use of iodine-containing medicinal preparations or radiographic contrast media. For this reason we intended to explore iodide excess impairment on prooxidant/antioxidant balance of the thyroid gland, hepatic tissue and in blood and the effect of selenium administration on oxidative stress markers under the same circumstances. Experiments were performed for 10 days with white, male, Wistar rats, as follows: group 1: control-normal iodine supply group; 2: high iodine diet, group; 3: high iodine diet and selenium; group 4: high iodine diet and Carbimasole. Oxidative stress markers such as lipid peroxides were determined in thyroid gland, hepatic tissue and in blood. Measuring H+ donor ability of the sera and catalase activity in thyroid gland and in hepatic tissue assessed antioxidant defense. Iodide excess had prooxidant effects, leading to an increased lipid peroxides level and catalase activity in target tissues and in blood and to a decreased H+ donor ability of the sera. Selenium supplementation had opposite effects. Present data allow us to conclude that the alterations due to iodide excess in thyroid gland, hepatic tissue and in blood are mediated through oxidative stress.     

Vitamin C deficiency in Channa punctatus Bloch

The results of a series of experiments on Channa punctatus previously conditioned to a complete synthetic diet and later fed vitamin C deficient diet for 210 days followed by 30 days of recovery with fortified vitamin C ration are reported. The survival, growth, morphological abnormalities and biochemical changes in tissue ascorbic acid and cholesterol levels were studied.
Deficiency of vitamin C resulted in a mortality of up to 25% and retarded growth accompanied by anorexia and loss of weight. Marked skeletal abnormalities, viz. , lordosis, scoliosis and degenerative changes in the thoracic vertebrae were revealed by X-ray studies. Biochemical investigations showed a significant decrease in blood and kidney ascorbic acid levels within a month of feeding the deficient diet. A prolonged deficiency beyond 150 days resulted in a rapid rise in the cholesterol content of the liver. These biochemical changes were reversed when vitamin C was added to the ration.     

Effects of Iodine-131 in sheep depending on the content of stable iodine in the diet]

The biological effect of 131I was studied in sheep kept on a diet deficient in stable iodine. An increased capture and accretion of iodine in the thyroid gland and in the whole body were observed. The disturbances in the structure and function of the thyroid gland, liver and haemopoietic organs were more pronounced in the animals kept on the iodine deficient diet.     

Absorption of glyoxylate and oxalate in thiamine and pyridoxine deficient rat intestine

Dietary deficiency of thiamine or pyridoxine has been shown to produce hyperoxaluria and renal stone formation in man and experimental animals. To determine the possible contribution of exogenous glyoxylate and oxalate, the intestinal transport of [14C] - oxalate and [14C] - glyoxylate was measured in vitamin B1 and B6 deficient rats and their respective pair-fed controls. Results indicate that glyoxylate and oxalate are passively diffused from lumen to lamina propria in thiamine deficient and their pair-fed controls with no significant change in the rate of uptake of both the substrates. However B6 deficient rats showed a significant enhancement in the rate of oxalate uptake due to development of a new biphasic transport system. The rate of glyoxylate uptake by simple passive diffusion remained unaltered in pyridoxine deficiency.     

Experimental oxalate urolith formation in rats.

Urinary calculi composed of calcium oxalate were produced in male hooded Wistar rats fed a vitamin B6 deficient diet over 16 weeks. This basic diet was modified by doubling the phosphate content or loading with vitamin C or D3 in three treatment groups. The number of rats developing oxalate stones was not altered by the addition of vitamin D3 or phosphate, but there was a significant increase in total weight of stone formed and histological evidence of extensive renal damage in rats on the high vitamin D3 diet. The addition of vitamin C to the vitamin B6 deficient rats resulted in a reduction in the number of rats with uroliths and a fall in urinary oxalate excretion, while similarly loaded vitamin B6 supplemented controls were free of oxalate calculi. It is concluded that the oxalate urolithiasis induced by vitamin B6 deficiency was exacerbated by added vitamin D3 and reduced by vitamin C.     

Cassava is not a goitrogen in mice

To examine the effect of cassava on the thyroid function of mice, we fed fresh cassava root to mice and compared this diet with low iodine diet and Purina. Cassava provided a low iodine intake and increased urine thiocyanate excretion and serum thiocyanate levels. Mice on cassava lost weight. The thyroid glands of mice on cassava were not enlarged, even when normalized for body weight. The 4- and 24-hr thyroid uptakes of mice on cassava were similar to those of mice on low iodine diets. Protein-bound [125I]iodine at 24 hr was high in mice on either the cassava or low iodine diets. The thyroid iodide trap (T/M) was similar in mice on cassava and low iodine diets. When thiocyanate was added in vitro to the incubation medium, T/M was reduced in all groups of mice; under these conditions, thiocyanate caused a dose-related inhibition of T/M. The serum thyroxine (T4) and triiodothyronine (T3) concentrations of mice on cassava were reduced compared with mice on Purina diet. Thyroid T4 and T3 contents of mice on cassava were relatively low compared with mice on Purina diet. Hepatic T3 content and T4 5'-monodeiodination in liver homogenates were reduced in mice on cassava compared with other groups. The data show that cassava does not cause goiter in mice. The thiocyanate formed from ingestation of cassava is insufficient to inhibit thyroid iodide transport or organification of iodide. The cassava diet leads to rapid turnover of hormonal iodine because it is a low iodine diet. It also impairs 5'-monodeiodination of T4 which may be related to nutritional deficiency. These data in mice do not support the concept that cassava per se has goitrogenic action in man.     

Dietary selenium- and vitamin E-induced alterations in some rabbit tissues

The present study was designed to investigate and compare the effects of dietary selenium (Se) and vitamin E on some physiological parameters and histological changes in liver, heart, and skin tissues, as well as the blood parameters and the related enzymes. Both sex young rabbits were fed with deficient (9.8 μg/kg diet), adequate (225 μg/kg diet), and rich (4.2 mg/kg diet) Se and vitamin E diets for 12–15 wk for this purpose. As the plasma Se levels and the erythrocyte glutathione (GSH) peroxidase activity decreased (79.8±9.4 ng/ml and 2.0±0.3 U/g Hb, respectively) in the deficient group, these values increased (100.4±2.7 ng/mL and 14.5±4.3 U/g Hb) in the rich group significantly with respect to the control group. The other antioxidant enzyme activities and the related element levels did not change significantly in either one of the experimental groups. Although the platelet counts of the two experimental groups were not different from the control values, the collagen and the adenosine diphosphate (ADP) stimulated platelet aggregation rate and intensity increased in the deficient group (p<0.05) and decreased very significantly (p<0.001) in the rich group. In both of the experimental groups, as the percentage values of the neutrophils decreased, the lymphocytes and the eosinophils increased significantly. According to the light microscopic investigations, the observed lesions of considerable intensity within the tissues that elicit cell degenerations were more pronounced in the animals fed with the rich diet than in those fed with the deficient diet. The deficiency as well as toxicity of Se and the deficiency of vitamin E caused several alterations in the physiological functions of the tissues, and these alterations were supported by the histological lesions within these tissues.     

Iodine deficiency activates antioxidant genes and causes DNA damage in the thyroid gland of rats and mice

Because thyroid nodules are frequent in areas with iodine deficiency the aim of this study was to characterise molecular events during iodine deficiency that could explain mutagenesis and nodule formation. We therefore studied gene expression of catalytic enzymes prominent for H(2)O(2) detoxification and antioxidative defence, quantified DNA oxidation and damage as well as spontaneous mutation rates (SMR) in mice and rats fed an iodine controlled diet. Antioxidative enzymes such as superoxide dismutase 3, glutathione peroxidase 4 and the peroxiredoxins 3 and 5 showed increased mRNA expression, which indicates increased radical burden that could be the cause of additional oxidized base adducts found in thyroidal genomic DNA in our experiments of iodine deficiency. Furthermore, the uracil content of thyroid DNA was significantly higher in the iodine-deficient compared to the control group. While SMR is very high in the normal thyroid gland it is not changed in experimental iodine deficiency. Our data suggest that iodine restriction causes oxidative stress and DNA modifications. A higher uracil content of the thyroid DNA could be a precondition for C-->T transitions often detected as somatic mutations in nodular thyroid tissue. However, the absence of increased SMR would argue for more efficient DNA repair in response to iodine restriction.     

Effects of different dietary amounts of LCPUFA n3 and vitamin B6 on lipid composition and antioxidant defences in rat kidney

Our previous report demonstrated that, when vitamin deficiency is associated with high contents of long chain polyunsaturated fatty acids (LCPUFA) n3, lipid peroxidation susceptibility in rat heart and liver increases. In this paper, we evaluated the effect of the same dietary administration on lipid composition and antioxidant defenses of rat kidney. Results showed that vitamin B(6) deficiency, when associated with a fish oil diet, as compared to vegetable oil condition, increased relative kidney weight and decreased pyridoxal-5P contents. The different LCPUFA n3 dietary contents produced, on kidney phospholipids, effects interlaced with those of vitamin B(6) deficiency; in particular fish oil and vitamin B(6) deficient diet caused a significant decrease of arachidonic acid showing that the processes of elongation and desaturation of linoleic acid were slowed. Also, peroxidation susceptibility was higher, as demonstrated both by increased TBARS formation and glutathione peroxidase activity, and by decreased vitamin E contents and reduced glutathione/oxidized glutathione ratio.     

Changes in Blood-Brain Barrier Nutrient Transport in the Offspring of Iodine-Deficient Rats and Their Preventability

Thyroid hormones affect the structure and function of biological membranes. Whether or not they affect the Blood-Brain Barrier nutrient transport, the rate limiting membrane transport regulating nutrient supply to brain is to be established yet. That the impaired brain development and function seen in iodine deficiency could be due to such an effect has been assessed in situ by the brain uptake index (BUI) method in Wistar/NIN rat pups born to dams subjected to dietary iodine deficiency/rehabilitation for different times. Compared to controls (C), there was a significant decrease in the BUI values of 2-Deoxy-D-Glucose (2-DG) and L-leucine (Leu) in the pups (D1) born to dams chronically fed low iodine test (LIT) diet through their active growth and subsequent pregnancy and lactation. Surprisingly transport of L-Tyrosine (Tyr) and sucrose (the background marker) was not altered, nor was the BBB transport of all these nutrients affected by feeding LIT diet during the mothers' gestation (D2) and lactation (D3) only. The hypothyroidism in D1 pups was only moderate and preventable by rehabilitation of mothers with control diet from conception (R1) or parturition (R2), as were the changes in BBB nutrient transport. The results suggest that chronic material dietary iodine deficiency impairs BBB nutrient transport in the offspring and this could be prevented by their rehabilitation with iodine.     

Vitamin A deficiency induces prooxidant environment and inflammation in rat aorta

We evaluated whether nutritional vitamin A deficiency generates oxidative stress and inflammation in aorta. Wistar male rats (21 days old) were given free access to a control (8 mg retinol as retinyl palmitate/kg) or a vitamin A- deficient diet for three months. One group of deficient animals was fed with the control diet fifteen days before sacrifice. Thiobarbituric acid-reactive substances (TBARS) and nitrite concentration where both analyzed in serum and aorta. Aorta Copper-Zinc Superoxide dismutase (CuZnSOD), Glutathion peroxidase (GPx) and Catalase (CAT) activities were measured. In addition, binding activity of the nuclear factor- kB (NF-kB), inducible and endothelial Nitric Oxide synthase (iNOS and eNOS, respectively) and Ciclooxygenase-2 (COX-2) expressions were determinated in aorta. Rats fed the vitamin A- deficient diet were characterized by sub-clinical plasma retinol concentration and showed increased serum and aorta concentrations of TBARS compared to controls. Lower than control activities of CuZnSOD, GPx, and CAT were observed in aorta of the vitamin A- deficient group. The binding activity of NF- kB was higher in vitamin A- deficient animals than controls. In addition, NO production evaluated as nitrite concentration increased in aorta and serum, associated with a higher expression of iNOS, eNOS and COX-2 in aorta of vitamin A-deficient rats. The incorporation of vitamin A into the diet of vitamin A-deficient rats reverted the changes observed in TBARS level, CuZnSOD and GPx activities, nitrite concentration and also, iNOS, eNOS and COX-2 expression. Prooxidant environment and inflammation are induced by vitamin A deficiency in rat aorta.     

High bromide intake affects the accumulation of iodide in the rat thyroid and skin

The effect of a high bromide intake on the kinetics of iodide uptake and elimination in the thyroid and skin of adult male rats was studied. In rats fed a diet with sufficient iodine supply (>25 μg I/d), the iodide accumulation in the skin predominated during the first hours after ¹³¹I -iodide application. From this organ, radioiodide was gradually transferred into the thyroid. A high bromide intake (>150 mg Br⁻/d) in these animals led to a marked decrease in iodide accumulation, especially by the thyroid, because of an increase in iodide elimination both from the thyroid and from the skin. In rats kept under the conditions of iodine deficiency (<1 μ I/d), the iodide accumulation in the thyroid, but not in the skin, was markedly increased as a result of a thyrotropic stimulation. The effect of a high bromide intake (>100 mg Br⁻/d) in these animals was particularly pronounced because the rates of iodide elimination were most accelerated both from their thyroid and from their skin. Presented in part at the 20th Workshop on Macro and Trace Elements held in Jena (Germany) on December 1–2, 2000.     

Iron and zinc status in rats with diet-induced marginal deficiency of vitamin A and/or copper

The hypothesis was tested that there are interactions of marginal copper and vitamin A deficiency regarding iron and zinc status. Copper restriction (1 vs 5 mg Cu/kg diet) significantly lowered copper concentrations in plasma and tissues of rats and reduced blood hemoglobin, hematocrit, and iron concentrations in tibia and femur, but raised iron concentrations in liver. Vitamin A restriction (0 vs 4000 IU vitamin A/kg diet) reduced plasma retinol concentrations and induced a fall of blood hemoglobin and hematocrit. Neither copper nor vitamin A restriction for up to 42 d affected feed intake and body wt gain. There were no interrelated effects of vitamin A and copper deficiency on iron status. Copper deficiency slightly depressed liver, spleen, and kidney zinc concentrations. Vitamin A deficiency lowered zinc concentrations in heart, but only when the diets were deficient in copper.     

Down regulation of hypertrophied follicular cell volume in thyroid hyperplastic gland

In the present study, changes in thyroid follicular cell volume and its regulation have been investigated during the early involution of a hyperplastic goitre. Male Wistar rats were administered an iodine deficient diet for 6 months with propylthiouracil (PTU, 0.15%) during the last two months. At the end of iodine deficiency (day 0), some rats were killed and the others received a normal iodine diet. These rats were killed after different periods of iodine refeeding. Thyroid follicular cell volume was very high in hyperplastic gland whereas thyroid protein concentration was low. Thyroid follicular cell volume quickly decreased when rats were normally iodine refed, whereas thyroid protein concentration increased. Electron microscopal observations showed that thyroid follicular cells retained their endocrine aspect in hyperplastic state and throughout the iodine refeeding period. Using concomitant stereological and biochemical techniques, it is shown that the amount of cellular iodide and an unknown iodinated compound strongly increased during the early iodine refeeding. Plasma TSH was high on day 0 and remained at this level until day 8 whereas plasma T3 and T4 were low on day 0 and remained at this low level until day 4. The present data show that the involution of thyroid follicular cell volume is induced by iodide and mediated by an iodinated compound at least in the initial phase, and is independent of plasma TSH, T3, T4, so indicating the involvement of a thyroid autoregulatory mechanism. These changes in cell volume may be of importance in ion transport, i.e. in the metabolism of thyroid follicular cell during the early involution of the hyperplastic goitre.