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ABSTRACT: BACKGROUND & AIMS: Wogonin is a flavonoid extracted from the root of Scutellaria baicalensis Gerogi. We evaluated the therapeutic effects of wogonin using db/db mice. METHODS: Mice received wogonin or vehicle by oral gavage for 2 weeks. Blood glucose, insulin, and cholesterol levels were measured, and liver morphology was observed with histopathological analysis. The mRNA expression levels of PPARα, PPARγ, and adiponectin in the liver and white adipose tissue (WAT) were determined by real-time PCR. Immunoblotting for AMPK and PPARγ, and adipocyte differentiation were investigated in vitro using 3T3-L1 cells. A luciferase assay was used to measure PPARα and PPARγ binding activity. RESULTS: The wogonin group showed decreased weight gain without a change in food intake and improved glucose tolerance. Serum insulin and cholesterol levels in the wogonin group were significantly decreased compared to those in the control group. The wogonin group also showed less accumulation of lipid droplets and glycogen in the liver. PPARα and PPARγ expression levels in the liver and WAT and adiponectin expression level in WAT in the wogonin group were higher than those in the control group. In 3T3-L1 cells, wogonin was shown to stimulate AMPK activation in a dose-dependent manner. The presence of wogonin did not affect adipocyte differentiation or PPARγ protein level during adipogenesis. Notably, wogonin enhanced PPARα but not PPARγ transactivation. CONCLUSIONS: These indicate that wogonin may have beneficial effects on glucose and lipid metabolism related to enhanced PPARα and adiponectin expression via AMPK activation. Importantly, wogonin did not cause deleterious effects, such as weight gain and fatty liver. Wogonin might be a useful therapeutic agent to treat type 2 diabetes.
Clinical nutrition (Edinburgh, Scotland) 03/2013; · 3.27 Impact Factor
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ABSTRACT: The aim of this study was to analyze the response of gene expression caused by etoposide (VP-16) in the fetal mouse brain. Four miligrams/kilogram of VP-16 was intraperitoneally injected into pregnant mice on day 12 of gestation (GD 12). Gene expression profiling of the VP-16-treated fetal mouse brain by DNA microarray was performed. The expression changes of the target genes of p53 were also examined by real-time RT-PCR. VP-16 induced S-phase accumulation, G2/M arrest, and eventually apoptosis of neuroepithelial cells in the fetal brain. DNA microarray analysis revealed that 8 of cell cycle control- and apoptosis-related genes were upregulated and that 5 of DNA damage, repair, replication, and transcription genes were also upregulated in the fetal telencephalons at 4 h after VP-16 treatment (HAT). The results of real-time RT-PCR demonstrated that the expression of topoisomerase IIα was increased at 4 and 8 HAT. The expression of pro-apoptotic factors such as puma, noxa, bax, and cyclin G was also increased from 4 to 12 HAT. These results suggest that VP-16 induces DNA damage, DNA repair, cell cycle alternation, and apoptosis in the fetal mouse brain. In addition, VP-16-induced apoptosis is mediated through the mitochondrial pathway in a p53-related manner. The present study will provide a better understanding of the mechanisms of VP-16-induced fetal brain injury.
Experimental Animals 01/2013; 62(2):93-9. · 0.92 Impact Factor
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You Chan Bae, Gye Hyeong Woo,
Ha Young Kim,
Moon Her,
Dong Hee Cho,
Suk Chan Jung,
Jae Ku Oem,
Jae Won Byun,
Yi Seok Joo,
O Soo Lee,
Myoung Heon Lee
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ABSTRACT: Bovine brucellosis causes abortion and infertility. The authors conducted this study in order to determine pathological lesions of Korean native cows and fetuses who received experimental vaccination with Brucella abortus RB51 and were challenged with Brucella abortus 2308. Gross and histopathological lesions in endometrium and placenta were observed in cows of the vaccinated group. Twenty-five percent of pregnant cattle in the vaccinated group showed endometritis and placentitis, which was three times lower, compared with the non-vaccinated group. The pathological lesions in the uterus and placenta in both groups were consistent with previous reports. Therefore, vaccination in heifers using Brucella abortus RB51 may not provide adequate protection against infection with Brucella abortus virulent strain.
Korean Journal of Veterinary Public Health. 09/2012; 36(3):109-113.
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ABSTRACT: To elucidate target molecules of white matter development responding to hypothyroidism, global gene expression profiling of cerebral white matter from male rat offspring was performed after maternal exposure to anti-thyroid agents, 6-propyl-2-thiouracil and methimazole, on postnatal day 20. Genes involved in central nervous system development commonly up- or down-regulated among groups treated with anti-thyroid agents. Immunohistochemical distributions of vimentin, Ret proto-oncogene (Ret), deleted in colorectal cancer protein (DCC), and Claudin11 (Cld11) were examined based on the gene expression profile. Immunoreactive cells for vimentin and Ret in the cingulum, and the immunoreactive intensity of Cld11 and DCC in whole white matter were increased by treatment with anti-thyroid agents. Immunoreactive cells for vimentin and Ret were immature astrocytes and oligodendrocytes, respectively. Thus, immunoreactive cells for vimentin and Ret may be quantitatively measurable targets of developmental hypothyroidism in white matter.
Reproductive Toxicology 04/2012; 34(1):93-100. · 3.23 Impact Factor
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ABSTRACT: We immunohistochemically investigated the impact and reversibility of three brominated flame retardants (BFRs) known to be weak thyroid hormone disruptors on neuronal development in the hippocampal formation and apoptosis in the dentate subgranular zone. Pregnant Sprague-Dawley rats were exposed to 10, 100, or 1,000 ppm decabromodiphenyl ether (DBDE); 100, 1,000 or 10,000 ppm tetrabromobisphenol A (TBBPA) or 1,2,5,6,9,10-hexabromocyclododecane (HBCD) in the diet from gestational day 10 through to day 20 after delivery (weaning). On postnatal day (PND) 20, interneurons in the dentate hilus-expressing reelin increased with all chemicals, suggestive of aberration of neuronal migration. However, this increase had disappeared by PND 77. NeuN-positive mature neurons increased in the hilus on PND 77 with all chemicals. In the subgranular zone on PND 20, an increase in apoptotic bodies suggestive of impaired neurogenesis was observed after exposure to TBBPA or HBCD. The effects on neuronal development were detected at doses of ≥100 ppm DBDE; ≥1,000 ppm TBBPA; and at least at 10,000 ppm HBCD. On PND 20, the highest dose of DBDE and HBCD revealed mild fluctuations in the serum concentrations of thyroid-related hormones suggestive of weak developmental hypothyroidism, while TBBPA did not. Thus, DBDE and TBBPA may exert direct effect on neuronal development in the brain, but hypothyroidism may be operated for DBDE and HBCD at high doses. An excess of mature neurons in the hilus at later stages may be the signature of the developmental effects of BFRs. However, the effect itself was reversible.
Archive für Toxikologie 03/2012; 86(9):1431-42. · 4.67 Impact Factor
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Hong Gyu Park,
Eun Jung Bak, Gye-Hyeong Woo,
Jin Moon Kim,
Zhejiu Quan,
Jung Mogg Kim,
Ho-Kun Yoon,
Seung Hoon Cheon,
Goo Yoon,
Yun-Jung Yoo,
Younghwa Na,
Jeong-Heon Cha
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ABSTRACT: Licochalcone E (lico E) is a retrochalcone isolated from the root of Glycyrrhiza inflata. Retrochalcone compounds evidence a variety of pharmacological profiles, including anticancer, antiparasitic, antibacterial, antioxidative and superoxide-scavenging properties. In this study, we evaluated the biological effects of lico E on adipocyte differentiation in vitro and obesity-related diabetes in vivo. We employed 3T3-L1 preadipocyte and C3H10T1/2 stem cells for in vitro adipocyte differentiation study and diet-induced diabetic mice for in vivo study. The presence of lico E during adipogenesis induced adipocyte differentiation to a significant degree, particularly at the early induction stage. Licochalcone E evidenced weak, but significant, peroxisome proliferator-activated receptor gamma (PPARγ) ligand-binding activity. Two weeks of lico E treatment lowered blood glucose levels and serum triglyceride levels in the diabetic mice. Additionally, treatment with lico E resulted in marked reductions in adipocyte size and increases in the mRNA expression levels of PPARγ in white adipose tissue (WAT). Licochalcone E was also shown to significantly stimulate Akt signaling in epididymal WAT. In conclusion, lico E increases the levels of PPARγ expression, at least in part, via the stimulation of Akt signals and functions as a PPARγ partial agonist, and this increased PPARγ expression enhances adipocyte differentiation and increases the population of small adipocytes, resulting in improvements in hyperglycemia and hyperlipidemia under diabetic conditions.
The Journal of nutritional biochemistry 08/2011; 23(7):759-67. · 4.29 Impact Factor
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Reproductive Toxicology 07/2011; · 3.23 Impact Factor
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ABSTRACT: Chana series are new chalcone derivatives. To evaluate the possibility of Chana series as therapeutic agents of type 2 diabetes, the inhibitory effects of Chana series on the activities of α-glucosidase and DPP-4 were investigated using in vitro enzyme assays, and their effects on adipocyte differentiation were investigated in C3H10T1/2 cells. Chana 1 and Chana 7 among the Chana series showed significant inhibition of α-glucosidase activity. In DPP-4 enzyme assay, Chana 1 exhibited the highest inhibitory activity while Chana 7 did not. In MTT assay, Chana 1 did not show significant cytotoxicity up to a concentration of 250 μM, whereas cytotoxicity was observed with Chana 7 at a concentration of 300 μM. In addition, Chana 1 induced adipocyte differentiation. Therefore, Chana 1 showed inhibitory effects on α-glucosidase and DPP-4 as well as a stimulatory effect on adipocyte differentiation, suggesting that Chana 1 may be a potential beneficial agent for the treatment of type 2 diabetes.
BMB reports 06/2011; 44(6):410-4. · 1.72 Impact Factor
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ABSTRACT: Rat thyroid follicular cell carcinomas invading into the thyroid capsule are highly produced by promotion with sulfadimethoxine (SDM) in a rat two-stage thyroid carcinogenesis model. In this study, we investigated the participation of phosphoinositide 3-kinase (PI3K) signaling pathway that is associated with malignant phenotypes of many cancers on the development of SDM-induced capsular invasive carcinomas.
Thyroid proliferative lesions developed 10 or 15 weeks after promotion with SDM in male F344 rats initiated with N-bis(2-hydroxypropyl)nitrosamine were immunohistochemically analyzed with regard to cellular distribution of phosphatase and tensin homolog (PTEN) and Akt isoforms, as well as their downstream molecules.
Increased expression of PI3K signaling molecules was evident in association with the development of lesion stages from the early focal hyperplasia to the late carcinomas. Capsular carcinomas, and the less frequent parenchymal carcinomas, exclusively expressed phosphorylated, inactive PTEN, and active Akt isoforms, as did their downstream molecules. Among the Akt isoforms, enhanced expression of Akt1 was more prominent than that of Akt2 in both capsular and parenchymal carcinomas.
Activation of the PI3K pathway through phosphorylation of PTEN promotes the high production of capsular carcinomas as well as the development of less frequent parenchymal carcinomas.
Journal of Cancer Research and Clinical Oncology 04/2011; 137(4):723-32. · 2.56 Impact Factor
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ABSTRACT: Pregnant Sprague-Dawley rats were given diet containing decabromodiphenyl ether (DBDE) either at 0, 10, 100, or 1000 ppm from gestation day (GD) 10 until day 20 after delivery (PND 20). No significant alterations were observed in maternal and offspring reproductive parameters. At PND 20, serum triiodothyronine concentrations examined in males were slightly reduced at 1000 ppm (84.2% of the control value), and incidence of thyroid follicular cell hypertrophy was increased in both sexes with significant difference in males at 1000 ppm. Diffuse liver cell hypertrophy accompanying increased relative liver weight and increased cytoplasmic eosinophilia of the renal proximal tubules were observed in both sexes with significant difference from 10 ppm in males and females, respectively. At postnatal week 11, serum thyroxine concentrations examined in males were slightly reduced at 1000 ppm (85.9% of the control value), and the incidence of thyroid follicular cell hypertrophy was non-significantly increased from 10 ppm in males. There were reductions in the corpus callosum area and density of 2',3'-cyclic nucleotide 3'-phosphodiesterase-immunoreactive oligodendrocytes in the cingulate deep cortex in males from 100 ppm. Conversely, NeuN-immunoreactive neuronal distribution in the hippocampal CA1 was unchanged. This suggests that developmental DBDE-exposure caused irreversible white matter hypoplasia targeting oligodendrocytes from 100 ppm, accompanied with developmental hypothyroidism. The lowest-observed-adverse-effect level of DBDE was determined to be 10 ppm (0.7-2.4 mg/kg-body weight-d).
Reproductive Toxicology 01/2011; 31(1):86-94. · 3.23 Impact Factor
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ABSTRACT: We have shown phosphoinositide 3-kinase (PI3K)/Akt signaling activation in thyroid capsular invasive carcinomas (CICs), which are highly induced by promotion with sulfadimethoxine (SDM) in a rat 2-stage thyroid carcinogenesis model. To examine the potency of calcitriol, a synthetic vitamin D3 analog, on the development or progression of CICs, male F344 rats were injected with calcitriol (0.1 µg/kg body weight) three times a week intraperitoneally, during an entire period of SDM-promotion for 13 weeks (Experiment 1) or during the last 2 weeks of a 15-week SDM-promotion (Experiment 2). Initiation with N-bis(2-hydroxypropyl)nitrosamine preceded all treatments. In Experiment 1, long-term calcitriol treatment reduced the multiplicity of CICs, while cell proliferation activity, estimated by Ki-67 cell index in the induced CICs, was unchanged with SDM-promotion alone. Considering the strong dependency of promotion with SDM during the early stages on thyroid-stimulating hormone, the reduced multiplicity in Experiment 1 may be due to the effect on an early stage of neoplastic proliferation. Although the magnitude was mild, cell proliferation activity was decreased in existing CICs after short-term calcitriol treatment in Experiment 2, which was associated with a mild decrease in cyclin-dependent kinase-2-positive cells, cytoplasmic immunolocalization of phosphorylated, inactive, Rb protein and a mild increase in nucleocytoplasmic expression of p27(kip1). Although the effect was mild at the late stage of SDM-promotion in this hypothyroidism-related thyroid carcinogenesis model, our results suggest that calcitriol targets cell proliferation via inhibition of a molecular cascade downstream of PI3K/Akt signaling, controlling G1/S transition.
Journal of Veterinary Medical Science 12/2010; 73(5):655-64. · 0.85 Impact Factor
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ABSTRACT: Necrotizing sialometaplasia (NS) is a self-limiting, benign, ischemic, inflammatory disease that is most often described in the submandibular glands of dogs, with clinical and histologic features that resemble malignancy. Unilateral swelling of the parotid salivary gland in a 7-year-old Cocker Spaniel dog was diagnosed as NS. The dog also had otitis externa on the same side as the parotid gland lesions. The main histologic features were included lobular necrosis of salivary tissue; fibrinoid necrosis of some arteries; marked squamous metaplasia of duct and/or acinar epithelium, with intercellular bridge formation; preservation of salivary lobular morphology; and variable inflammation and fibrosis. Etiologic factors for NS in both humans and animals remain obscure.
Journal of veterinary diagnostic investigation: official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc 11/2010; 22(6):975-7. · 1.21 Impact Factor
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ABSTRACT: A dead whooper swan was found in an area of cropland near a stream and was submitted to the National Veterinary Research and Quarantine Service (NVRQS) in Korea. The affected animal was in relatively good condition. Grossly, the heart was enlarged and had pale and dark red stripes. A white, elongate parasite was seen on the cut surface of the heart. Histopathologically, severe lymphohistiocytic inflammation, myocardial necrosis, many adult heart worms and microfilariae were observed in the myocardium. Hemorrhage, lymphocytic inflammation, mineralization, and myocardial degeneration were also seen around the adult worms. No bacteria or viruses were isolated from the affected bird. The pathological findings indicate that the whooper swan was infected with nematodes, presumably Sarconema eurycerca, resulting in non-suppurative myocarditis.
Journal of Veterinary Medical Science 09/2010; 72(9):1233-5. · 0.85 Impact Factor
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ABSTRACT: Over a 6-day period beginning on 15 October 2008, 93 dead or sick wild waterfowl, including Mallards, Spotbills, and teal species, were found along the shore of a branch stream of the Hangang River, which flows through Seoul, Korea, and were submitted to the National Veterinary Research and Quarantine Service (NVRQS) for diagnosis. Clinically, the affected birds showed flaccid paralysis of the legs and wings and paralysis of the neck. Grossly, no bird showed any lesions, but all had almost empty stomachs. Histopathologic findings included mild lymphocytic hepatitis and mild lymphocytic interstitial nephritis. Clostridium botulinum type C toxin was identified in sera collected from the birds using a mouse bioassay for botulinum toxins; however, no bacteria were isolated from any of the affected birds. In addition, a low-pathogenic avian influenza virus was isolated from two Spotbills, and pesticides such as diazinon and phorate, were detected in seven Mallards. The cause of this outbreak is not clear, but an increase in organic materials from sewage due to drought, increased temperatures, and an increased number of aquatic carcasses resulting from pesticide contamination may have increased the replication of C. botulinum, contributing to the release of botulinum toxins into the waterfowl food chain.
Journal of wildlife diseases 07/2010; 46(3):951-5. · 1.08 Impact Factor
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ABSTRACT: Fifteen 8-month-old fennec foxes imported from Sudan showed fever, mucopurulent ocular discharge, diarrhea, severe emaciation, seizures, and generalized ataxia, and died. Three of the 15 animals were presented for diagnostic investigation. Severe dehydration, brain congestion, and gastric ulcers were observed in all animals. In one animal, the lungs had failed to collapse and were multifocally dark red in appearance. Histopathologically, there were lymphohistiocytic meningoencephalitis with malacia, mild interstitial pneumonia, lymphoid depletion of lymphoid tissues and organs, and intestinal villous atrophy with intralesional coccidia. There were many intracytoplasmic and/or intranuclear inclusion bodies in the epithelial cells of the medullary velum, lungs, liver, kidneys, trachea, pancreas, stomach, gall bladder, urinary bladder, and ureters, and in macrophages of malacia foci and lymphocytes and macrophages of lymphoid organs. Additionally, intestinal coccidia were confirmed to be Isospora species by a fecal test. To our knowledge, this is the first report of canine distemper with intestinal coccidiosis in fennec fox.
Journal of Veterinary Medical Science 03/2010; 72(8):1075-9. · 0.85 Impact Factor
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ABSTRACT: To detect molecular evidence reflecting a permanent disruption of neuronal development due to hypothyroidism, distribution of Reelin-producing cells that function in neuronal migration and positioning was analyzed in the hippocampal dentate hilus using rats. From gestation day 10, maternal rats were administered either 6-propyl-2-thiouracil (PTU) at 3 or 12ppm (0.57 or 1.97mg/kg body weight/day) or methimazole (MMI) at 200ppm (27.2mg/kg body weight/day) in the drinking water and male offspring were immunohistochemically examined at the end of exposure on weaning (postnatal day 20) and at the adult stage (11-week-old). Offspring with MMI and 12ppm PTU displayed evidence of growth retardation lasting into the adult stage. On the other hand, all exposure groups showed a sustained increase in Reelin-expressing cells in the dentate hilus until the adult stage in parallel with Calbindin-D-28K-expressing cells at weaning and with glutamic acid decarboxylase 67-positive cells in the adult stage, confirming an increase in gamma-aminobutyric acid (GABA)ergic interneurons. At the adult stage, NeuN-positive postmitotic mature neurons were also increased in the hilus in all exposure groups, however, the increased population of Reelin-producing cells at this stage was either weakly positive or negative for NeuN, indicative of immature neurons. At weaning, neuroblast-producing subgranular zone of the dentate gyrus showed increased apoptosis and decreased cell proliferation suggestive of impaired neurogenesis. The results suggest that sustained increases of immature GABAergic interneurons synthesizing Reelin in the hilus could be a signature of compensatory regulation for impaired neurogenesis and mismigration during the neuronal development as a hypothyroidism-related brain effect rather than that secondary to systemic growth retardation.
Reproductive Toxicology 03/2010; 29(4):407-14. · 3.23 Impact Factor
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Yukie Saegusa, Gye-Hyeong Woo,
Hitoshi Fujimoto,
Kaoru Inoue,
Miwa Takahashi,
Masao Hirose,
Katsuhide Igarashi,
Jun Kanno,
Kunitoshi Mitsumori,
Akiyoshi Nishikawa,
Makoto Shibutani
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ABSTRACT: To determine whether developmental hypothyroidism causes permanent disruption of neuronal development, we first performed a global gene expression profiling study targeting hippocampal CA1 neurons in male rats at the end of maternal exposure to anti-thyroid agents on weaning (postnatal day 20). As a result, genes associated with nervous system development, zinc ion binding, apoptosis and cell adhesion were commonly up- or down-regulated. Genes related to calcium ion binding were up-regulated and those for myelination were often down-regulated. We, then, examined immunohistochemical cellular distribution of Ephrin type A receptor 5 (EphA5) and Tachykinin receptor (Tacr)-3, those selected based on the gene expression profiles, in the hippocampal formation at the adult stage (11-week-old) as well as at the end of exposure. At weaning, both EphA5- and Tacr3-immunoreactive cells with strong intensities appeared in the pyramidal cell layer or stratum oriens of the hippocampal CA1 region. Although the magnitude of the change was decreased at the adult stage, Tacr3 in the CA1 region showed a sustained increase in expressing cells until the adult stage after developmental hypothyroidism. On the other hand, EphA5-expressing cells did not show sustained increase at the adult stage. The results suggest that developmental hypothyroidism caused sustained neuronal expression of Tacr3 in the hippocampal CA1 region, probably reflecting a neuroprotective mechanism for mismigration.
Journal of Veterinary Medical Science 11/2009; 72(2):187-95. · 0.85 Impact Factor
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ABSTRACT: An outbreak of fatal hemorrhagic pneumonia with 70-90% morbidity and 50% mortality occurred in an animal shelter in Yangju, Gyeonggi Province, Korea. Clinically, the affected dogs showed severe respiratory distress within 48 h after arriving in the shelter. The dead were found mainly with nasal bleeding and hematemesis. At necropsy, hemothorax and hemorrhagic pneumonia along with severe pulmonary consolidation was observed, though histopathological analysis showed mainly hemorrhagic bronchopneumonia. Lymphoid depletion was inconsistently seen in the spleen, tonsil and bronchial lymph node. Gram-positive colonies were shown in blood vessels or parenchyma of cerebrum, lung, liver, spleen, and kidney. Also, Streptococcus (S.) equi subsp. zooepidemicus was isolated from the various organs in which the bacterium was microscopically and histologically detected. In addition, approximately 0.9 Kb specific amplicon, antiphagocytic factor H binding protein, was amplified in the bacterial isolates. In this study, we reported an outbreak of canine hemorrhagic bronchopneumonia caused by S. equi subsp. zooepidemicus in an animal shelter in Yangju, Korea.
Journal of veterinary science (Suwŏn-si, Korea) 10/2009; 10(3):269-71. · 0.89 Impact Factor
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Hye-Ryoung Kim,
Choi-Kyu Park,
Youn-Jeong Lee, Gye-Hyeong Woo,
Kyoung-Ki Lee,
Jae-Ku Oem,
Seong-Hee Kim,
Young-Hwa Jean,
Yu-Chan Bae,
Soon-Seek Yoon,
In-Soon Roh,
Ok-Mi Jeong,
Ha-Young Kim,
Jeong-Soo Choi,
Jae-Won Byun,
Yun-Kyung Song,
Jun-Hun Kwon,
Yi-Seok Joo
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ABSTRACT: In spite of intensive surveillance programs for the control of HPAI, an outbreak of highly pathogenic avian influenza (HPAI) H5N1 in Korea in April 2008 caused serious damage to poultry farms, as did previous outbreaks in 2003/2004 and 2006/2007. Six viruses were selected from the Korean 2008 isolates for genetic analysis, and all eight gene segments from each of the influenza viruses were sequenced. A phylogenetic analysis showed that all of the viruses were of the same virus type and that the hemagglutinin (HA) gene was clustered with that of clade 2.3.2 viruses. However, the internal and neuraminidase (NA) genes were closely related to those of the clade 2.3.4 viruses (recent human and bird isolates from Southeast Asia).
Veterinary Microbiology 09/2009; 141(3-4):362-6. · 3.33 Impact Factor
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ABSTRACT: To evaluate developmental exposure effects of two brominated flame retardants, tetrabromobisphenol A (TBBPA) and 1,2,5,6,9,10-hexabromocyclododecane (HBCD), pregnant Sprague-Dawley rats were administered either chemical at doses of 100, 1000 or 10,000 ppm in a soy-free diet from gestation day 10 until the day 20 after delivery. Offspring exposed to TBBPA showed dose-unrelated slight decreases of serum triiodothyronine (T(3)) concentration at postnatal day 20, and there was no evidence of hypothyroidism-related neuronal mismigration and impaired oligodendroglial development as judged by morphometric analyses of NeuN-immunoreactive neuronal distribution in the hippocampal CA1, and area of corpus callosum as well as density of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase)-immunoreactive oligodendrocytes in the cingulate deep cortex at the adult stage. On the other hand, HBCD exerted a weak hypothyroidism evident with increases in thyroid weight, thyroid follicular cell hypertrophy and serum concentrations of thyroid-stimulating hormone as well as decreases of serum T(3) concentrations in offspring at 10,000 ppm at weaning. Increased thyroid weights and decreased serum T(3) concentrations were also observed in the adult stage from 1000 ppm. With regard to the effect on brain development, HBCD reduced density of CNPase-positive oligodendrocytes at 10,000 ppm, suggesting an impaired oligodendroglial development. Results thus suggest that TBBPA did not exert developmental brain effects, while HBCD did, and 100 ppm was determined to be the no-observed-adverse-effect level of HBCD from changes in thyroid parameters at the adult stage by maternal exposure, translating into 8.1-21.3mg/kg-d.
Reproductive Toxicology 08/2009; 28(4):456-67. · 3.23 Impact Factor
