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Tris(4-hydroxyphenyl)ethane (THPE), a trisphenol compound, is antiestrogenic and can retard uterine development in CD-1 mice
2020
Xiao, Han | Wang, Yue | Jia, Xiaojing | Yang, Lei | Wang, Xiaoning | Guo, Xuan | Zhang, Zhaobin
Tris (4-hydroxyphenyl)ethane (THPE), a trisphenol compound widely used as a branching agent and raw material in plastics, adhesives, and coatings is rarely regarded with concern. However, inspection of in vitro data suggests that THPE is an antagonist of estrogen receptors (ERs). Accordingly, we aimed to evaluate the antiestrogenicity of THPE in vivo and tested its effect via oral gavage on pubertal development in female CD-1 mice. Using uterotrophic assays, we found that THPE either singly, or combined with 17β-estradiol (E₂) (400 μg/kg bw/day) suppressed the uterine weights at low doses (0.1, 0.3, and 1 mg/kg bw/day) in 3-day treatment of weaning mice. When mice were treated with THPE during adolescence (for 10 days beginning on postnatal day 24), their uterine development was significantly retarded at doses of at least 0.1 mg/kg bw/day, manifest as decreased uterine weight, atrophic endometrial stromal cells and thinner columnar epithelial cells. Transcriptome analyses of uteri demonstrated that estrogen-responsive genes were significantly downregulated by THPE. Molecular docking shows that THPE fits well into the antagonist pocket of human ERα. These results indicate that THPE possesses strong antiestrogenicity in vivo and can disrupt normal female development in mice at very low dosages.
Mostrar más [+] Menos [-]Programming of hepatic lipid metabolism in a rat model of postnatal nicotine exposure – Sex-related differences
2020
Bertasso, Iala Milene | Pietrobon, Carla Bruna | Lopes, Bruna Pereira | Peixoto, Thamara Cherem | Soares, Patrícia Novaes | Oliveira, Elaine | Manhães, Alex Christian | Bonfleur, Maria Lucia | Balbo, Sandra Lucinei | Cabral, Suellen Silva | Gabriel Kluck, George Eduardo | Atella, Georgia Correa | Gaspar de Moura, Egberto | Lisboa, Patrícia Cristina
Maternal nicotine exposure during lactation induces liver damage in adult male rats. However, the mechanism in males is unknown and females have not been tested. Here, we determined the liver lipid composition and lipogenic enzymes in male and female offspring at two ages in a model of postnatal nicotine exposure. Osmotic minipumps were implanted in lactating Wistar rat dams at postnatal day (PND) 2 to release 6 mg/kg/day of nicotine (NIC group) or saline (CON group) for 14 days. Offspring received a standard diet from weaning until euthanasia at PND120 (1 pup/litter/sex) or PND180 (2 pups/litter/sex). At PND120, NIC males showed lower plasma triglycerides (TG), steatosis degree 1, higher hepatic cholesterol (CHOL) ester, free fatty acids, monoacylglycerol content as well as acetyl-coa carboxylase-1 (ACC-1) and fatty acid synthase (FAS) protein expression in the liver compared to CON males. At this age, NIC females had preserved hepatocytes architecture, higher plasma CHOL, higher CHOL ester and lower total CHOL content in the liver compared to CON females. At PND180, NIC males showed steatosis degrees 1 and 2, higher TG, lower free fatty acids and total CHOL content in the liver and an increase in ACC-1 hepatic protein expression. NIC females had higher plasma TG and CHOL levels, no change in hepatic morphology, lower CHOL ester and free fatty acids in the liver, which also showed higher total ACC-1 and FAS protein expression. Maternal nicotine exposure induces long-term liver dysfunction, with an alteration in hepatic cytoarchitecture that was aggravated with age in males. Concerning females, despite unchanged hepatic cytoarchitecture, lipid metabolism was compromised, which deserves further attention.
Mostrar más [+] Menos [-]Reconstructing temporal variation of fluoride uptake in eastern grey kangaroos (Macropus giganteus) from a high-fluoride area by analysis of fluoride distribution in dentine
2016
Kierdorf, Horst | Rhede, Dieter | Death, Clare | Hufschmid, Jasmin | Kierdorf, Uwe
Trace element profiling in the incrementally formed dentine of mammalian teeth can be applied to reconstruct temporal variation of incorporation of these elements into the tissue. Using an electron microprobe, this study analysed fluoride distribution in dentine of first and third mandibular molars of free-ranging eastern grey kangaroos inhabiting a high-fluoride area, to assess temporal variation in fluoride uptake of the animals. Fluoride content in the early-formed dentine of first molars was significantly lower than in the late-formed dentine of these teeth, and was also lower than in both, the early and the late-formed dentine of third molars. As early dentine formation in M1 takes place prior to weaning, this finding indicates a lower dentinal fluoride uptake during the pre-weaning compared to the post-weaning period. This is hypothetically attributed to the action of a partial barrier to fluoride transfer from blood to milk in lactating females and a low bioavailability of fluoride ingested together with milk. Another factor contributing to lower plasma fluoride levels in juveniles compared to adults is the rapid clearance of fluoride from blood plasma in the former due to their intense skeletal growth. The combined action of these mechanisms is considered to explain why in kangaroos from high-fluoride areas, the (early-formed) first molars are not affected by dental fluorosis while the (later-formed) third and fourth molars regularly exhibit marked to severe fluorotic lesions.
Mostrar más [+] Menos [-]Short and long-term effects of bisphenol S (BPS) exposure during pregnancy and lactation on plasma lipids, hormones, and behavior in rats
2019
da Silva, Beatriz Souza | Pietrobon, Carla Bruna | Bertasso, Iala Milene | Lopes, Bruna Pereira | Carvalho, Janaine Cavalcanti | Peixoto-Silva, Nayara | Santos, Tatianne Rosa | Claudio-Neto, Sylvio | Manhães, Alex Christian | Oliveira, Elaine | de Moura, Egberto Gaspar | Lisboa, Patrícia Cristina
Bisphenol S (BPS) has replaced bisphenol A (BPA), a known non-persistent endocrine disrupting chemical, in several products. Considering that little is known regarding BPS effects, especially during critical windows of ontogenetic development, and that BPA, which is quite similar to BPS, is know to be transferred to the offspring via the placenta and milk, in the present study we investigated the behavioral, biochemical and endocrine profiles of Wistar rats born from dams that were BPS-exposed [groups: BPS10 (10 μg/kg/day), BPS50 (50 μg/kg/day)] during pregnancy and lactation. Due to the non-monotonic dose-response effect of bisphenol, the data of both BPS groups were directly compared with those of the controls, not to each other. Males and females were analyzed separately. At weaning, male BPS50 offspring had hypotriglyceridemia and hyperthyroxinemia, whereas BPS50 females showed higher 25(OH)D levels. At adulthood, BPS offspring of both sexes had lower food intake. BPS males showed lower visceral adiposity. BPS50 females had smaller fat droplets in brown adipocytes. BPS males showed higher anxiety and higher locomotor activity, while BPS10 females showed lower exploration. During a food challenge test at adulthood, BPS males consumed more high-fat diet at 30 min. BPS10 females initially (at 30 min) consumed more high-fat diet but, after 12 h, less of this diet was consumed. BPS50 males had hypertriglyceridemia and lower plasma T3, while BPS females showed lower plasma T4. BPS10 females had lower progesterone, whereas BPS50 females had higher plasma 25(OH)D. Maternal BPS exposure has adverse effects on the triacylglycerol, hormones levels and behavior of the progeny. Furthermore, the increased preference for the fat-enriched diet suggests an increased risk for obesity and its health consequences in the long term.
Mostrar más [+] Menos [-]Perinatal exposure to low-dose decabromodiphenyl ethane increased the risk of obesity in male mice offspring
2018
Yan, Sen | Wang, Dezhen | Teng, Miaomiao | Meng, Zhiyuan | Yan, Jin | Li, Ruisheng | Jia, Ming | Yao, Chenyang | Sheng, Jing | Tian, Sinuo | Zhang, Renke | Zhou, Zhiqiang | Zhu, Wentao
Decabromodiphenyl Ethane (DBDPE), a kind of new brominated flame retardants (NBFRs) used to replace DecaBDE, has been frequently detected in the environment and human samples. In this study, we explored its toxic effects on male mouse offspring after perinatal exposure to DBDPE. During the perinatal period, pregnant ICR mice were exposed to DBDPE (100 μg/kg body weight) via oral gavage. After weaning, male offspring were fed on a low-fat diet and a high-fat diet, respectively. We measured and recorded body weight, liver weight, and epididymis fat mass, blood biochemical markers, metabolites changes in liver, and gene expression involved in lipid and glucose homeostasis. The results showed that perinatal exposure to DBDPE increased the risk of obesity in mouse offspring and affected triglyceride synthesis, bile secretion, purine synthesis, mitochondrial function and glucose metabolism, furthermore, the use of HFD feeding may further exacerbate these effects. All of these results show that early-life exposure to low doses of DBDPE can promote the development of metabolic dysfunction, which in turn induces obesity.
Mostrar más [+] Menos [-]Drivers and annual estimates of marine wildlife entanglement rates: A long-term case study with Australian fur seals
2015
McIntosh, Rebecca R. | Kirkwood, Roger | Sutherland, Duncan R. | Dann, Peter
Methods of calculating wildlife entanglement rates are not standardised between studies and often ignore the influence of observer effort, confounding comparisons. From 1997–2013 we identified 359 entangled Australian fur seals at Seal Rocks, south-eastern Australia. Most entanglement materials originated from commercial fisheries; most frequently entangling pups and juveniles. Using Generalized Additive Mixed Models, which incorporated observer effort and survey frequency, we identified that entanglements were observed more frequently amongst pups from July to October as they approached weaning. Neither the decline in regional fishing intensity nor changing seal population size influenced the incidence of entanglements. Using the models, we estimated that 302 (95% CI=182–510) entangled seals were at Seal Rocks each year, equivalent to 1.0% (CI=0.6–1.7%) of the site population. This study highlights the influence of observer effort and the value of long-term datasets for determining the drivers of marine debris entanglements.
Mostrar más [+] Menos [-]Synergistic oxidative impact of aluminum chloride and sodium fluoride exposure during early stages of brain development in the rat
2019
Kinawy, Amal A.
Aluminum is widely used in industry and in cooking utensils, especially in countries with low economic and social standards. Fluoride is also used in industry, a major component of toothpaste and is added to the drinking water in many countries to fight teeth decay and cavities. Consequently, the coexistence of aluminum and fluoride is highly probable. Growing evidence indicates that environmental pollutants during the early stages of embryonic development may reprogram the offspring’s brain capabilities to encounter oxidative stress during the rest of their postnatal life. This study investigated the impact of sodium fluoride (NaF, 0.15 g/L) and aluminum chloride (AlCl₃, 500 mg/L) added, individually or in combination, to the deionized drinking water starting from day 6 of gestation until just after weaning, or until the age of 70 days postnatal life. A significant decline was observed in tissue contents of vitamin C, reduced glutathione, GSH/GSSH ratio, and the total protein, as well as in the activities of Na⁺/K⁺-ATPase and superoxide dismutase (SOD) in almost all cases. On the contrary, lipid peroxidation and NO, as total nitrate, exhibited a significant increase in comparison with the corresponding control. Based on the present results, administration of Al and NaF, alone or in combination abated the quenching effects of the antioxidant system and induced oxidative stress in most brain regions under investigation. In conclusion, aluminum and fluoride are very noxious environmental pollutants that interfere with the proper functions of the brain neurons and their combination together aggravates their hazard.
Mostrar más [+] Menos [-]Maternal exposure to perfluorooctanoic acid (PFOA) causes liver toxicity through PPAR-α pathway and lowered histone acetylation in female offspring mice
2019
Li, Danyang | Zhang, Linchao | Zhang, Yan | Guan, Shuo | Gong, Xincheng | Wang, Xiaodan
The study was conducted to investigate the liver toxicity in female offspring mice induced by maternal exposure to perfluorooctanoic acid (PFOA). Fifty pregnant Kunming mice were randomly divided into 5 groups with 10 of each, which were treated with 0.2 mL PFOA solution dissolved with deionized water at 0, 1, 2.5, 5, and 10 mg/kg BW, respectively, from the pregnancy day (PND) 0 to day 17. Female offspring mice were sacrificed to collect serum and liver at postpartum day 21. The results showed that PFOA significantly reduced the body weight at weaning and the survival rate of the female offspring mice (P < 0.01) increased the liver index of the pups (P < 0.01). Meanwhile, PFOA also caused hepatic bleeding, local necrosis, and enlargement of hepatocytes and vacuolization. The levels of serum AST, ALT, SOD, and CAT in PFOA treatment group were upregulated significantly (P < 0.01). The expressions of Acot1, Acox1, and Acsl1 genes were increased significantly (P < 0.01). The expression of PPAR-α gene was decreased significantly (P < 0.01). There was no significant difference in the expression of Cpt1a gene among the 5 groups. HAT activity was reduced significantly and HDAC activity was increased significantly. The expression of anti-acetyl-histone H3 and acetyl-histone H4 was reduced significantly. Thus, our findings indicate that exposure to PFOA during pregnancy affects the growth and development of the pups and causes liver damage, disrupting the secretion of enzymes involved in fatty acid oxidation induced by PPAR-α, leading to liver oxidative stress and a decrease in the degree of histone acetylation. Elevated HDAC may aggravate downstream fatty acid metabolism disorders through PPAR-α.
Mostrar más [+] Menos [-]Behavioral and neurochemical consequences of perinatal exposure to lead in adult male Wistar rats: protective effect by Centella asiatica
2018
Chintapanti, Swetha | Pratap Reddy, K. | Sreenivasula Reddy, P.
The present study evaluated the protective effects of Centella asiatica (CA) leaf extract on behavioral deficits and neurotoxicity in adult rat exposed to lead during perinatal period. Adult Wistar rats were exposed to 0.15% lead acetate (Pb) from gestation day 6 through drinking water and the pups were exposed lactationally to Pb till weaning. Significant perturbations in locomotor activity and exploratory behavior were observed in rats exposed to Pb during perinatal period. The levels of lipid peroxidation increased significantly with a reduction in levels of glutathione and activity levels of acetylcholinesterase and antioxidant enzymes in hippocampus, cerebrum, cerebellum, and medulla of brains excised from Pb-exposed rats. Oral supplementation of CA during postweaning period provided significant protection against Pb-induced behavioral impairments and neurotoxicity, without chelating tissue Pb levels. The possible neuroprotective efficacy of CA may be due to its antioxidant potential but not by lowering effects of brain Pb content.
Mostrar más [+] Menos [-]Oxidative Stress and DNA methylation in male rat pups provoked by the transplacental and translactational exposure to bisphenol A
2020
El Henafy, Hanan M. A. | Ibrahim, Marwa A. | Abd El Aziz, Samy A. | Gouda, Eman M.
The epigenetic changes induced by environmental contaminants play important roles in the inheritance of male reproductive dysfunction. The present study investigated DNA methylation changes and some oxidative stress biomarkers induced by bisphenol A (BPA) in male offspring. A total number of 48 female albino rats were administered orally with 50 μg/kg of BPA/day during gestation and/or lactation periods. At postnatal day 60, the samples were collected from the male pups to assess the serum testosterone, malondialdehyde (MDA) level, superoxide dismutase (SOD), glutathione S-transferase, and glutathione peroxidase (GSH-Px) activities in testicular tissue. DNA methylation in both DNA (cytosine-5)-methyltransferase 3A and estrogen receptor alpha genes was detected by methylation-specific PCR. BPA exposure resulted in significant decrease in the anogenital distance, testis and epididymis weights, serum testosterone level, SOD, GST, and GSH-Px levels with significant increase in weaning body weight and the MDA level. Additionally, BPA caused marked hypermethylation within Dnmt3A and ER- ∝ genes promoter regions in the testis of rat male pups. Graphical abstract
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