خيارات البحث
النتائج 1 - 10 من 17
Probiotics inhibit the stunted growth defect of perfluorobutanesulfonate via stress and thyroid axes in zebrafish larvae
2021
Perfluorobutanesulfonate (PFBS) is an emerging pollutant in aquatic environments and potently disrupts the early developmental trajectory of teleosts. Considering the persistent and toxic nature of PFBS, it is necessary to develop in situ protective measures to ameliorate the toxic damage of PFBS. Probiotic supplements are able to mitigate the growth retardation defects of PFBS. However, the interactive mechanisms remain elusive. To this end, this study acutely exposed zebrafish larvae to a concentration gradient of PFBS (0, 1, 3.3 and 10 mg/L) for 4 days, during which probiotic bacteria Lactobacillus rhamnosus were added in the rearing water. After exposure, alterations in gene transcriptions and key hormones along the hypothalamus–pituitary–interrenal (HPI), growth hormone/insulin–like growth factor (GH/IGF) and hypothalamus–pituitary–thyroid (HPT) axes were examined. The results showed that PFBS single exposure significantly increased the cortisol concentrations, suggesting the induction of stress response, while probiotic supplementation effectively decreased the cortisol levels in coexposed larvae in an attempt to relieve the stress of PFBS toxicant. It was unexpected that probiotic additive significantly decreased the larval GH concentrations independent of PFBS, thereby eliminating the contribution of GH/IGF axis to the growth improvement of probiotics. In contrast, probiotic bacteria remarkably increased the concentration of thyroid hormones, particularly the thyroxine (T4), in zebrafish larvae. The pronounced down-regulation of uridinediphosphate glucoronosyltransferases (UDPGT) gene pointed to the blocked elimination process of T4 by probiotics. Furthermore, proteomic fingerprinting found that probiotics were potent to shape the protein expression pattern in PFBS-exposed zebrafish larvae and modulated multiple biological processes that are essential for the growth. In summary, the present findings suggest that HPI and HPT axes may cooperate to enhance the growth of fish larvae under PFBS and probiotic coexposures.
اظهر المزيد [+] اقل [-]Contaminants in Atlantic walruses in Svalbard Part 2: Relationships with endocrine and immune systems
2019
Routti, Heli | Diot, Béatrice | Panti, Cristina | Duale, Nur | Fossi, Maria Cristina | Harju, Mikael | Kovacs, Kit M. | Lydersen, Christian | Scotter, Sophie E. | Villanger, Gro D. | Bourgeon, Sophie
Marine mammals in the Barents Sea region have among the highest levels of contaminants recorded in the Arctic and the Atlantic walrus (Odobenus rosmarus rosmarus) is one of the most contaminated species within this region. We therefore investigated the relationships bewteen blubber concentrations of lipophilic persistent organic pollutants (POPs) and plasma concentrations of perfluoroalkyl substances (PFASs) and markers of endocrine and immune functions in adult male Atlantic walruses (n = 38) from Svalbard, Norway. To do so, we assessed plasma concentrations of five forms of thyroid hormones and transcript levels of genes related to the endocrine and immune systems as endpoints; transcript levels of seven genes in blubber and 23 genes in blood cells were studied. Results indicated that plasma total thyroxine (TT4) concentrations and ratio of TT4 and reverse triiodothyronine decreased with increasing blubber concentrations of lipophilic POPs. Blood cell transcript levels of genes involved in the function of T and B cells (FC like receptors 2 and 5, cytotoxic T-lymphocyte associated protein 4 and protein tyrosine phosphatase non-receptor type 22) were increased with plasma PFAS concentrations. These results suggest that changes in thyroid and immune systems in adult male walruses are linked to current levels of contaminant exposure.
اظهر المزيد [+] اقل [-]Species-specific debromination of polybromodiphenyl ethers determined by deiodinase activity in fish
2019
Luo, Yuan-Lai | Luo, Xiao-Jun | Ye, Mei-Xia | Lin, Lan | Zeng, Yan-Hong | Mai, Bi-Xian
A combination of previous studies and the present study indicated species-specific debromination of polybromodiphenyl ethers (PBDEs) in teleost fish. Three situations of debromination were found, namely rapid debromination represented by debromination of BDE 99 to BDE 47 observed in common carp, tilapia, crucian carp, and oscar fish; slow debromination represented by debromination of BDE 99 to BDE 49 observed in the abovementioned fish and rainbow trout, salmon, and snakehead; and no or minor debromination observed in catfish. The results of experiments on cofactors, inhibitors, and substrate competitors indicated that activities of outer ring deiodinase of 3, 3′, 5′-triiodothyronine (type I deiodinase), which cannot be inhibited by 6-propyl-2-thiouracil, were responsible for the rapid debromination, and the outer ring deiodinase of thyroxine (type II deiodinase) regulated the slow debromination. The debromination of BDE 99 to BDE 49 was more common, but occurred at a much lower rate (approximately 100 times lower) than the debromination of BDE 99 to BDE 47. This was because the activity of type II deiodinase was nearly two orders of magnitude lower than that of type I deiodinase in the fish species studied. Further studies on debromination of PBDEs and properties of deiodinase in more species are needed to confirm the hypothesis.
اظهر المزيد [+] اقل [-]Illuminated night alters behaviour and negatively affects physiology and metabolism in diurnal zebra finches
2019
Batra, Twinkle | Malik, Indu | Kumar, Vinod
Light at night (LAN) negatively impacts the behaviour and physiology; however, very little is known about molecular correlates of LAN-induced effects in diurnal animals. Here, we assessed LAN-induced effects on behaviour and physiology, and examined molecular changes in the liver of diurnal zebra finches (Taeniopygia guttata). Birds were exposed to dim LAN (dLAN: 12L = 150 lux: 12D = 5 lux), with controls on 12L (150 lux): 12D (0 lux). dLAN altered daily activity-rest and eating patterns, induced nocturnal eating and caused body fattening and weight gain, and reduced nocturnal melatonin levels. Concomitant increased nighttime glucose levels, decreased daytime thyroxine and triglycerides levels, and hepatic lipid accumulation suggested the impairment of metabolism under dLAN. Transcriptional assays evidenced dLAN-induced negative effects on metabolism in the liver, the site of metabolic homeostasis. Particularly, increased g6pc and foxo1 mRNA expressions suggested an enhanced gluconeogenesis, while increased egr1 and star expressions suggested enhanced cholesterol biosynthesis and lipid metabolism, respectively. Similarly, overexpressed sirt1 indicated protection from the metabolic damage due to elevated gluconeogenesis and cholesterol biosynthesis under dLAN. However, no effect on genes involved in lipogenesis (fasn) and insulin signalling pathway (socs3 and insig1) might indicate for the post transcriptional/post translational modification effects or the involvement of other genetic pathways in LAN-induced effects. We also found daily rhythm in the hepatic expression of selected clock and clock-controlled genes (per2, bmal1 and reverb-beta), with an elevated mesor and amplitude of per2 oscillation, suggesting a role of per2 in the liver metabolism. These results demonstrate dLAN-induced negative effects on the behaviour and physiology, and provide molecular insights into metabolic risks of the exposure to illuminated nights to diurnal animals including humans in an urban setting.
اظهر المزيد [+] اقل [-]Polybrominated diphenyl ethers (PBDEs) and thyroid hormones in cord blood
2017
Ding, Guodong | Yu, Jing | Chen, Limei | Wang, Caifeng | Zhou, Yijun | Hu, Yi | Shi, Rong | Zhang, Yan | Cui, Chang | Gao, Yu | Tian, Ying | Liu, Fang
Human exposure to polybrominated diphenyl ethers (PBDEs) has been increasing over the last three decades in China and around the world. Animal studies suggest that PBDEs could reduce blood levels of thyroid hormones, but it is unclear whether PBDEs disrupt thyroid function in humans. We used data from a prospective birth cohort of 123 pregnant women who were enrolled between September 2010 and March 2011 in Shandong, China. We measured the concentrations of eight PBDE congeners (n = 106) and five thyroid hormones (n = 107) in cord serum samples. We examined the relationship between prenatal exposure to PBDEs and thyroid function (n = 90). Median concentrations of BDEs 47, 99, 100, and 153 (detection frequencies > 75%) were 3.96, 8.27, 3.31, and 1.89 ng/g lipid, respectively. A 10-fold increase in BDE-99 and Σ4 PBDEs (the sum of BDEs 47, 99, 100, and 153) concentrations was associated with a 0.41 μg/dL (95% confidence interval [CI]: 0.10 to 0.72) and 0.37 μg/dL (95% CI: 0.06 to 0.68) increase in total thyroxine levels (TT4), respectively. No associations were found between other individual congeners and any of the five thyroid hormones. Our study suggests that prenatal exposure to PBDEs may be associated with higher TT4 in cord blood. Given the inconsistent findings across existing studies, our results need to be confirmed in additional studies.
اظهر المزيد [+] اقل [-]Short-term exposure of arsenite disrupted thyroid endocrine system and altered gene transcription in the HPT axis in zebrafish
2015
Sun, Hong-Jie | Li, Hong-Bo | Xiang, Ping | Zhang, Xiaowei | Ma, Lena Q.
Arsenic (As) pollution in aquatic environment may adversely impact fish health by disrupting their thyroid hormone homeostasis. In this study, we explored the effect of short-term exposure of arsenite (AsIII) on thyroid endocrine system in zebrafish. We measured As concentrations, As speciation, and thyroid hormone thyroxine levels in whole zebrafish, oxidative stress (H2O2) and damage (MDA) in the liver, and gene transcription in hypothalamic–pituitary–thyroid (HPT) axis in the brain and liver tissues of zebrafish after exposing to different AsIII concentrations for 48 h. Result indicated that exposure to AsIII increased inorganic As in zebrafish to 0.46–0.72 mg kg−1, induced oxidative stress with H2O2 being increased by 1.4–2.5 times and caused oxidative damage with MDA being augmented by 1.6 times. AsIII exposure increased thyroxine levels by 1.3–1.4 times and modulated gene transcription in HPT axis. Our study showed AsIII caused oxidative damage, affected thyroid endocrine system and altered gene transcription in HPT axis in zebrafish.
اظهر المزيد [+] اقل [-]Perfluoroalkyl substances and thyroid hormones in cord blood
2017
Tsai, Meng-Shan | Lin, Ching-Chun | Chen, Mei-Huei | Hsieh, Wu-Shiun | Chen, Pau-Chung
Perfluoroalkyl substances (PFASs) are pollutants that tend to accumulate in the environment and organisms. The animal and human studies to date have focused on thyroid function, but the results are inconsistent.A sample of 118 mother-infant pairs was obtained from the Taiwan Birth Panel Study (TBPS). Cord blood PFASs levels were evaluated using the Waters ACQUITY UPLC system coupled with a Waters Quattro Premier XE triple quadrupole mass spectrometer, and cord blood thyroid hormones were assessed using a Roche Analytics E170 modular analyser (Roche Diagnostics, Mannheim, Germany). PFASs concentrations were analysed in the final models to examine the associations between cord blood PFASs levels and thyroid hormone concentrations.The cord blood perfluorooctane sulfonate (PFOS) concentration was negatively associated with the cord blood thyroxine (T4) concentration [per ln unit: adjusted β (95% confidence interval, CI) = −0.458(−0.916, −0.001)]. Moreover, the level of cord blood thyroid stimulating hormone (TSH) was positively associated with the cord blood PFOS concentration [per ln unit: adjusted β (95% confidence interval, CI) = 0.346(0.101, 0.592)]. The sex stratified effects of PFOS on T4 were suggestive of differential effects in high-exposure groups compared with low-exposure group in boys.We found that cord blood thyroid hormone levels are affected by PFASs, with a negative association between T4 and PFOS and a positive association between TSH and PFOS. The causal associations of thyroid hormones and PFASs require further exploration.
اظهر المزيد [+] اقل [-]TBBPA exposure during a sensitive developmental window produces neurobehavioral changes in larval zebrafish
2016
Tetrabromobisphenol A (TBBPA), one of the most widely used brominated flame retardants (BFRs), is a ubiquitous contaminant in the environment and in the human body. This study demonstrated that zebrafish embryos exposed to TBBPA during a sensitive window of 8–48 h post-fertilization (hpf) displayed morphological malformations and mortality. Zebrafish exposed exclusively between 48 and 96 hpf were phenotypically normal. TBBPA was efficiently absorbed and accumulated in zebrafish embryos, but was eliminated quickly when the exposure solution was removed. Larval behavior assays conducted at 120 hpf indicated that exposure to 5 μM TBBPA from 8 to 48 hpf produced larvae with significantly lower average activity and speed of movement in the normal condition than in those exposed from 48 to 96 hpf. Specifically, 8–48 hpf-exposed larvae spent significantly less time in both activity bursts and gross movements compared to control or 48–96 hpf exposed larvae. Consistent with the motor deficits, TBBPA induced apoptotic cell death, delayed cranial motor neuron development, inhibited primary motor neuron development and loosed muscle fiber during the early developmental stages. To further explore TBBPA-induced developmental and neurobehavioral toxicity, RNA-Seq analysis was used to identify early transcriptional changes following TBBPA exposure. In total, 1969 transcripts were significantly differentially expressed (P < 0.05, FDR < 0.05, 1.5-FC) upon TBBPA exposure. Functional and pathway analysis of the TBBPA transcriptional profile identified biological processes involved in nerve development, muscle filament sliding and contraction, and extracellular matrix disassembly and organization changed significantly. In addition, TBBPA also led to an elevation in the expression of genes encoding uridine diphosphate glucuronyl transferases (ugt), which could affect thyroxine (T4) metabolism and subsequently lead to neurobehavioral changes. In summary, TBBPA exposure during a narrow, sensitive developmental window perturbs various molecular pathways and results in neurobehavioral deficits in zebrafish.
اظهر المزيد [+] اقل [-]Testing for heterotopia formation in rats after developmental exposure to selected in vitro inhibitors of thyroperoxidase
2021
Ramhøj, Louise | Frädrich, Caroline | Svingen, Terje | Scholze, Martin | Wirth, Eva K. | Rijntjes, Eddy | Köhrle, Josef | Kortenkamp, Andreas | Axelstad, Marta
The thyroperoxidase (TPO) enzyme is expressed by the thyroid follicular cells and is required for thyroid hormone synthesis. In turn, thyroid hormones are essential for brain development, thus inhibition of TPO in early life can have life-long consequences for brain function. If environmental chemicals with the capacity to inhibit TPO in vitro can also alter brain development in vivo through thyroid hormone dependent mechanisms, however, remains unknown. In this study we show that the in vitro TPO inhibiting pesticide amitrole alters neuronal migration and induces periventricular heterotopia; a thyroid hormone dependent brain malformation. Perinatal exposure to amitrole reduced pup serum thyroxine (T4) concentrations to less than 50% of control animals and this insufficiency led to heterotopia formation in the 16-day old pup’s brain. Two other in vitro TPO inhibitors, 2-mercaptobenzimidazole and cyanamide, caused reproductive toxicity and had only minor sporadic effects on the thyroid hormone system; consequently, they did not cause heterotopia. This is the first demonstration of an environmental chemical causing heterotopia, a brain malformation until now only reported for rodent studies with the anti-thyroid drugs propylthiouracil and methimazole. Our results highlight that certain TPO-inhibiting environmental chemicals can alter brain development through thyroid hormone dependent mechanisms. Improved understanding of the effects on the brain as well as the conditions under which chemicals can perturb brain development will be key to protect human health.
اظهر المزيد [+] اقل [-]Mediation effects of thyroid function in the associations between phthalate exposure and glucose metabolism in adults
2021
Huang, Han-Bin | Siao, Chi-Ying | Lo, Yuan-Ting C. | Shih, Shu-Fang | Lu, Chieh-Hua | Huang, Po-Chin
The mediating influence of thyroid function on the association of phthalate exposure with glucose metabolism, including insulin resistance, remains unclear. We explored the mediating influence of thyroid hormone levels on the phthalate exposure–insulin resistance association. This cross-sectional study of 217 Taiwanese adults assessed insulin resistance (Homeostatic Model Assessment for Insulin Resistance, HOMA-IR scores) and the levels of 11 urinary phthalate metabolites and 5 thyroid hormones. Multiple regression models were used to analyze the associations among serum thyroid hormone levels, urinary phthalate metabolite levels, and HOMA-IR scores. The mediation analysis assessed the influence of thyroid function on the phthalate exposure–HOMA-IR association. Our data indicated urinary mono-ethylhexyl phthalate (MEHP) levels was negatively associated with free thyroxine (T₄) (β = −0.018; 95% confidence interval [CI]: −0.031, −0.005) and positively associated with HOMA-IR scores (β = 0.051, 95% CI: 0.012, 0.090). The study also revealed urinary mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) levels was negatively associated with free T₄ (β = −0.036, 95% CI: −0.056, −0.017) and HOMA-IR (β = 0.070, 95% CI: 0.013, 0.126). Free T₄ and HOMA-IR had a negative association (β = −0.757, 95% CI: −1.122, −0.392). In the mediation analysis, free T₄ mediated 24% and 35% of the associations of urinary MEHP and MEOHP with HOMA-IR, respectively. Our findings revealed the mediating role of thyroid function in the phthalate exposure–glucose metabolism association in adults.
اظهر المزيد [+] اقل [-]