scholarly journals Toxicology of Repeated Iodine Thyroid Blocking in Adult Rat

2018 ◽  
Vol 3 (1) ◽  

Radioactive iodines emitted following nuclear accidents are responsible for the dramatic increase of the late-onset thyroid cancer. Until the Fukushima disaster, a single dose of potassium iodide (KI) has been considered as an efficient countermeasure. Indeed, recently it has been suggested that repeated administration of KI may be necessary to ensure adequate protection in case of protracted exposure. Whereas, the effect of a single dose of KI has largely been studied ensuring its safety, studies regarding adverse effects of repeated iodine thyroid blocking (ITB) administration are scarce. Our objective was to assess the long term overall impact of KI in adult rats after repeated intake. Adult Wistar rats were subjected to either KI or saline solution over eight days. Biochemical homeostasis, hormones level, autoimmunity status, thyroid morphology and thyroid transcriptome profile were analyzed thirty days after the discontinuation of KI administration. Biochemical parameters, plasma levels of TSH; thyroid hormones; anti-TPO and anti-Tg did not differ between treated and control rats, the thyroid histology was not affected by the treatment and no long term transcriptome signature attributable to the treatment was noticed. Based on these data, we conclude the safety of repeated KI intake in adult rats; these data are prominent and may contribute to the ongoing development of KI guidelines and marketing authorization.

1995 ◽  
Vol 74 (4) ◽  
pp. 1793-1799 ◽  
Author(s):  
M. L. Errington ◽  
T. V. Bliss ◽  
G. Richter-Levin ◽  
K. Yenk ◽  
V. Doyere ◽  
...  

1. We examined the efficacy of low-frequency trains (1-5 Hz) in producing long-term depression (LTD) or depotentiation in the hippocampus of the awake adult rat and in anesthetized rats aged from 10 days to 3 mo. 2. In the dentate gyrus we found no evidence that low-frequency trains produce either depotentiation or LTD in the awake, adult animal or in the anesthetized animal at any age tested (10 days-adult). 3. In area CA1 of both awake and anesthetized adult rats, we also found no evidence that low-frequency trains induced either LTD or depotentiation. Only in area CA1 of very young rats (10-11 days) was clear evidence for LTD and depotentiation obtained; at this age experiments were only possible in anesthetized animals. By 16 days, the ability to display both LTD and depotentiation was lost. 4. These experiments suggest that repetitive low-frequency stimulation evokes a developmentally regulated form of activity-dependent depression that in the hippocampus is limited to specific pathways in the young animal. Our results leave open the question of whether alternative patterns of activity can induce LTD and/or depotentiation in the adult awake rat.


Reproduction ◽  
2009 ◽  
Vol 138 (3) ◽  
pp. 519-525 ◽  
Author(s):  
Xiaohui Deng ◽  
Hua Zheng ◽  
Xuan Yu ◽  
Hongling Yu ◽  
Chengmei Zhang ◽  
...  

The functional longevity of cryopreserved ovarian grafts is one of the most challenging questions regarding ovarian transplantation at present. This study used a rat ovarian grafting model to investigate whether ovarian tissues from adult rats, which had been cryopreserved by vitrification and followed by heterotopic transplantation, could establish long-term hormone secretion and follicle development. Fresh and cryopreserved ovarian tissues were autologously transplanted under the kidney capsule. One-third of the animals in each group (sham-operated, fresh autografts, cryopreserved autografts, or castrated) were killed 5, 8, or 10 months after transplantation. Vaginal cytology, serum estradiol (E2), progesterone, and the morphology of the reproductive tract were used to assess ovarian function. Both fresh and cryopreserved ovarian grafts survived well in all the animal models with comparable proportion of follicles at each stage of folliculogenesis at all three time points. The serum E2 and progesterone concentrations in the groups with fresh or cryopreserved grafts remained comparable with those in sham-operated controls at all investigated time points. However, a loss of grafts and primordial follicles following heterotopic transplantation was noted. In conclusion, the heterotopic autotransplantation of vitrified ovarian tissues from adult rat without vascular anastomosis can maintain long-term ovarian function and exert endocrine function in target organs, in spite of the reduction in follicle pool.


2008 ◽  
Vol 104 (5) ◽  
pp. 1287-1294 ◽  
Author(s):  
Anita Pawar ◽  
Ying-Jie Peng ◽  
Frank J. Jacono ◽  
Nanduri R. Prabhakar

Previous studies suggest that carotid body responses to long-term changes in environmental oxygen differ between neonates and adults. In the present study we tested the hypothesis that the effects of chronic intermittent hypoxia (CIH) on the carotid body differ between neonates and adult rats. Experiments were performed on neonatal (1–10 days) and adult (6–8 wk) males exposed either to CIH (9 episodes/h; 8 h/day) or to normoxia. Sensory activity was recorded from ex vivo carotid bodies. CIH augmented the hypoxic sensory response (HSR) in both groups. The magnitude of CIH-evoked hypoxic sensitization was significantly greater in neonates than in adults. Seventy-two episodes of CIH were sufficient to evoke hypoxic sensitization in neonates, whereas as many as 720 CIH episodes were required in adults, suggesting that neonatal carotid bodies are more sensitive to CIH than adult carotid bodies. CIH-induced hypoxic sensitization was reversed in adult rats after reexposure to 10 days of normoxia, whereas the effects of neonatal CIH persisted into adult life (2 mo). Acute intermittent hypoxia (IH) evoked sensory long-term facilitation of the carotid body activity (sensory LTF, i.e., increased baseline neural activity following acute IH) in CIH-exposed adults but not in neonates. The effects of CIH were associated with hyperplasia of glomus cells in neonatal but not in adult carotid bodies. These observations demonstrate that responses to CIH differ between neonates and adults with regard to the magnitude of sensitization of HSR, susceptibility to CIH, induction of sensory LTF, reversibility of the responses, and morphological remodeling of the chemoreceptor tissue.


Endocrinology ◽  
2013 ◽  
Vol 154 (1) ◽  
pp. 400-409 ◽  
Author(s):  
Kazuki Hattori ◽  
Nobuyuki Shirasawa ◽  
Hikaru Suzuki ◽  
Takanobu Otsuka ◽  
Ikuo Wada ◽  
...  

In the transitional zone of the rat anterior pituitary, spontaneous and LHRH-induced Ca2+ dynamics were visualized using fluo-4 fluorescence Ca2+ imaging. A majority of cells exhibited spontaneous Ca2+ transients, while small populations of cells remained quiescent. Approximately 70% of spontaneously active cells generated fast, oscillatory Ca2+ transients that were inhibited by cyclopiazonic acid (10 μm) but not nicardipine (1 μm), suggesting that Ca2+ handling by endoplasmic reticulum, but not Ca2+ influx through voltage-dependent L-type Ca2+ channels, plays a fundamental role in their generation. In the adult rat anterior pituitary, LHRH (100 μg/ml) caused a transient increase in the Ca2+ level in a majority of preparations taken from the morning group rats killed between 0930 h and 1030 h. However, the second application of LHRH invariably failed to elevate Ca2+ levels, suggesting that the long-lasting refractoriness to LHRH stimulation was developed upon the first challenge of LHRH. In contrast, LHRH had no effect in most preparations taken from the afternoon group rats euthanized between 1200 h and 1400 h. In the neonatal rat anterior pituitary, LHRH caused a suppression of spontaneous Ca2+ transients. Strikingly, the second application of LHRH was capable of reproducing the suppression of Ca2+ signals, indicating that the refractoriness to LHRH had not been established in neonatal rats. These results suggest that responsiveness to LHRH has a long-term refractoriness in adult rats, and that the physiological LHRH surge may be clocked in the morning. Moreover, LHRH-induced excitation and associated refractoriness appear to be incomplete in neonatal rats and may be acquired during development.


1983 ◽  
Vol 23 (4) ◽  
pp. 257-265 ◽  
Author(s):  
T. C. Marrs ◽  
E. Clifford ◽  
H. F. Colgrave

Hamsters and rats exposed to single doses of CS were retained for up to 32 months, together with appropriate controls. Survival was unaffected and in no case was the incidence of histological changes significantly higher in the test animals than corresponding control animals. The overall incidence of neoplastic disease was similar in test and control animals. A high incidence of pituitary acidophil adenomas was detected in the female rats: these tumours were present both in control and test rats and it was concluded that they were probably the result of ad libitum feeding. It was concluded that single doses of CS of 28 800 mg min m−3 administered during 1 hour or 18 000 mg min m−3 administered over 2 hours produced no long-term adverse effects in the two species studied.


1985 ◽  
Vol 63 (4) ◽  
pp. 279-282 ◽  
Author(s):  
Peter Walker

Perinatal thyroid dysfunction in the rat leads to permanent alterations in pituitary TSH secretion in the adult animal. Thus, neonatal hyperthyroidism (NH) and perinatal hypothyroidism (PH) both result in apparent increased pituitary sensitivity to the feedback effects of thyroid hormones in the adult rat. To determine if increased intrapituitary generation of triiodothyronine (T3) might account for these observations, we measured thyroxine (T4) 5′-deiodinase activity in pituitary homogenates of adult NH and PH rats. NH was induced by injecting neonatal rats with 12 daily sc injections of T4 (0.4 μg/g body weight (BW)). Control rats received vehicle alone. PH was induced by administering 0.05% 6-n-propylthiouracil in the drinking water to pregnant dams from the 16th day of gestation through the 12th day postpartum. Thereafter, a normal water supply was substituted. NH and PH rats were allowed to mature and were sacrificed at 105 days of age. Serum T4, T3, and TSH concentrations were measured by radioimmunoassay. Pituitary T4 5′-deiodinase activity was assessed by the measurement of T3 formation by pituitary homogenates incubated in the presence of 0.65 μM T4 and 100 mM dithiothreitol at 37 °C for 90 min. Body weights of adult NH and PH rats were slightly but not significantly decreased compared with control rats. Relative pituitary gland weight (milligrams per 100 g BW) was significantly decreased in adult PH rats (P < 0.005) but not in adult NH rats. In adult NH rats, serum T4 and T3 concentrations were significantly decreased (P < 0.01) compared with control rats. Serum TSH concentrations were similar. No significant differences in serum T4, T3, and TSH concentrations were noted between adult PH and control rats. Pituitary T4 5′-deiodinase activity was significantly increased in both adult NH and PH rats compared with controls (NH > PH > control; P < 0.005, and P < 0.05, respectively). These data indicate that pituitary T4 5′-deiodinase activity is significantly increased in adult NH and PH rats. Increased pituitary T4 5′-monodeiodination may explain, in part, the apparent increased thyrotroph sensitivity to feedback effects of thyroid hormone in these animals.


1996 ◽  
Vol 134 (5) ◽  
pp. 655-659 ◽  
Author(s):  
Sompongse Suwanwalaikorn ◽  
Boonsong Ongphiphadhanakul ◽  
Lewis E Braverman ◽  
Daniel T Baran

Suwanwalaikorn S, Ongphiphadhanakul B, Braverman LE, Baran DT. Differential responses of femoral and vertebral bones to long-term excessive l-thyroxine administration in adult rats. Eur J Endocrinol 1996;134:655–9. ISSN 0804–4643 Recent studies suggest that thyroid-stimulating hormone suppressive doses of thyroid hormone decrease bone mass in humans and growing rats. To determine the long-term effects of excessive l-thyroxine administration on the femur and vertebrae in an adult rat model, 20 male Sprague-Dawley rats (20 weeks old) were randomized into two groups. Group 1 received l-thyroxine (20 μg/100 g body weight ip daily), and group 2 received normal saline ip daily for 20 weeks. Femoral and lumbar vertebral bone mineral density measurements were performed at 0, 6, 15, 18 and 20 weeks of treatment. After 20 weeks of treatment, total RNA was isolated from both femoral and lumbar bones. Northern hybridization was performed with 32P-labeled DNA probes for osteocalcin, osteopontin, alkaline phosphatase and tartrate-resistant acid phosphatase. Significant decreases in bone mineral density in the femur of l-thyroxine-treated rats were observed after 15 weeks (p < 0.03). Lumbar bone mineral density was not affected. Both osteoblast (osteocalcin, osteopontin, alkaline phosphatase) and osteoclast (tartrate-resistant acid phosphatase) gene expression markers were increased significantly in the femoral bone (p < 0.001), but not in the lumbar vertebrae of the l-thyroxine-treated rats. We conclude that long-term administration of excessive doses of l-thyroxine to the adult rat preferentially affects femoral but not vertebral bone. This is manifested by decreased bone mineral density as well as increased gene expression markers for osteoblast and osteoclast activity in the femur. Daniel T Baran, Department of Orthopedics, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA


2006 ◽  
Vol 95 (6) ◽  
pp. 3519-3527 ◽  
Author(s):  
Jianqun Wu ◽  
Michael J. Rowan ◽  
Roger Anwyl

The induction of NMDA-receptor–dependent long-term potentiation (LTP) in adult CA1 is contingent on activation of Ca/calmodulin-dependent protein kinase II (CaMKII). However, little is known about kinase mediation of LTP in the dentate gyrus. In the present study, the involvement of the kinases CaMKII, PKA, and MAPK in the induction of LTP was studied in the dentate gyrus of adult rats. Individual application of selective inhibitors of CaMKII, MEK, or PKA did not inhibit induction of LTP. In contrast, coapplication of a CaMKII inhibitor with either a PKA or MEK inhibitor resulted in a strong block of LTP. Induction of LTP was blocked by the coapplication of the inhibitors CaMKII and PKA or MEK, both when they were applied 1 h before the induction stimulus and also when they were applied after the induction stimulus. Thus LTP is mediated by either of two parallel cascades, one involving CaMKII and the other PKA or MAPK. Moreover, these cascades are active for a certain period after the induction stimulus.


2018 ◽  
Vol 50 (06) ◽  
pp. 491-503 ◽  
Author(s):  
Ana Santos-Silva ◽  
Egberto de Moura ◽  
Cintia Pinheiro ◽  
Elaine Oliveira ◽  
Patricia Lisboa

AbstractNeonates can be exposed to bisphenol A (BPA) through placenta and milk, and BPA is associated with disorders such as precocious puberty and obesity. We evaluated the effects of BPA exposure during breastfeeding on the biochemical and endocrine profiles in young and adult rat progeny. From postnatal day (PND) 3 to 15 dams were divided into low-dose BPA treatment [50 μg/kg/day s.c. (BPA-LD)], high-dose BPA treatment [5 mg/kg/day s.c. (BPA-HD)], and Control (vehicle) groups. Milk was collected at PND15 and 21, which represents the end of exposure and 6 days after withdrawal, respectively. Dams were euthanized at weaning. Offspring of both genders were euthanized at PND15, 21, and 180. Milk estradiol levels were lower in the BPA-HD group than in the control group at PND 15; however, they were higher at PND21. Female rats whose mothers were BPA-exposed showed more significant differences from those in the control group, including better glycemic control and lipid profiles and higher food intake without higher adiposity, in adulthood than in the weaning period, when they presented with higher adiposity and hyperestrogenism. Conversely, male rats showed more abnormalities after BPA exposure compared to control rats, including insulin, leptin, testosterone, and thyroid hormone changes, when young but exhibited fewer alterations in adulthood, with increase only in LDLc in the BPA-HD rats. Taken together, the present findings suggest that exposure to BPA exclusively through milk affects adiposity, metabolism, and/or hormones of offspring in the short and long term, possibly compromising normal development in both sexes.


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