Ciências Fisiológicas
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Navegando Ciências Fisiológicas por Autor "Alves, Leandro Miranda"
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- ItemAVALIAÇÃO DA EXPOSIÇÃO AO TRIBUTILESTANHO NOS PARÂMETROS MORFOLÓGICOS E METABÓLICOS EM RATOS EXPOSTOS AO FRIO(Universidade Federal do Espírito Santo, 2022-06-30) Merlo, Eduardo; Graceli, Jones Bernardes; https://orcid.org/0000000193494369; http://lattes.cnpq.br/3803670746263603; https://orcid.org/0000-0003-0155-1472; http://lattes.cnpq.br/; Rodrigues, Livia Carla de Melo; https://orcid.org/; http://lattes.cnpq.br/2084216553746326; Alves, Leandro Miranda; https://orcid.org/0000-0001-7832-8717; http://lattes.cnpq.br/9883547704448526; Santos, Roger Lyrio dos; https://orcid.org/0000-0003-4316-7196; http://lattes.cnpq.br/1122196233280741; Lima, Leandro Ceotto Freitas; https://orcid.org/0000-0001-9550-6095Tributyltin (TBT) chloride is an endocrine-disrupting chemical linked with several metabolic complications. Brown adipose tissue (BAT) is emerging as a therapeutic target for metabolic complications. However, few studies have evaluated the TBT effect on BAT function. This study assessed whether a TBT exposure (100 ng/kg/day for 15 days via gavage) could modulate BAT morphophysiology. We evaluated the BAT parameters at room temperature (23ºC) and after a cold tolerance test (CTT – 6ºC) conditions. Interestingly, were observed low T4 levels in TBT rats under normal temperatures. A reduction in body temperature was observed in both conditions in TBT rats, suggesting an abnormal thermogenic function. BAT morphology irregularities were observed in TBT rats. Specifically, an increase in BAT lipid accumulation and unilocular adipocyte number. TBT also reduced lipid droplets and multilocular adipocyte number at room temperature. All these parameters were opposite in the CTT condition. Inflammation signals were observed in the TBT BAT. Collagen accumulation in TAM increased in the ambient condition, exacerbating in the cold condition in TBT rats. ROS production increased under both conditions. Finally, we observed negative correlations between body temperature and BAT lipid accumulation, BAT lipid accumulation and T4 levels, and multilocular adipocyte number. Conversely, and positive correlation was observed between BAT lipid accumulation, inflammation, and ROS production. Thus, these data suggest that the subacute and low dose of TBT exposure impaired BAT morphophysiology linked with lipid accumulation, inflammation, fibrosis, and oxidative stress in male rats.
- ItemEfeitos da sobrecarga crônica de ferro sobre a reprodutividade de camundongos(Universidade Federal do Espírito Santo, 2022-07-25) Alexandre, Jandinay Gonzaga; Santos, Leonardo dos; https://orcid.org/0000-0002-4340-6364; http://lattes.cnpq.br/4132087001362623; http://lattes.cnpq.br/3456911181567441; Alves, Leandro Miranda; https://orcid.org/0000-0001-7832-8717; http://lattes.cnpq.br/9883547704448526; Graceli, Jones Bernardes; https://orcid.org/0000000193494369; http://lattes.cnpq.br/3803670746263603Iron is an essential metal for body homeostasis, acquired from a diet rich in red meat and grains and vegetables, but iron overload (chronic Fe) can cause damage to organs such as the heart, vessels, liver, pancreas and , also, in the organs of the reproductive system. Studies evaluating the effects of iron overload on the hypothalamic-pituitary-gonadal (HPG) axis in the literature are particularly scarce. The objective of this dissertation is to study the effects of chronic iron overload on the reproductive system and reproductive capacity of female mice. We used female mice (C57BL/6) and two experimental groups, control and Fe 10 mg/Kg. The animals destined to the Fe group received intraperitoneal (i.p) injections of iron-dextran (10mg/kg/day, 5x/week), while the animals in the control group received saline solution (0.9% NaCl) in the same volume, conditions and time period. Consecutively, for 30 days, the estrous cycle of the animals was evaluated through a vaginal smear properly stained with methanol, hematoxylin and eosin. At the end of the exposure, a reproductive assay was performed with some animals and other animals were anesthetized and euthanized for removal and consequently obtaining the organs involved in the hypothalamic-pituitary-gonadal axis for analysis. In our results, it was possible to identify a decrease in the size of the ovary, uterus and hypothalamus. It was also noticeable the accumulation of iron in the liver, spleen, hypothalamus, ovary and uterus. The estrous cycle of mice was deregulated. The histology of the ovaries showed impaired follicular development, with a numerical reduction of corpus luteum and an increase in the number of atretic follicles. Histology showed uterine hypotrophy. Even with Fe suppression, the estrous cycle was not normalized and when we quantified the litter, no pups were registered in the cages of animals belonging to the Fe group. These results suggest that chronic exposure to iron generated hemosiderosis, harming the organs involved in the hypothalamic-pituitary-gonadal axis, promoting a reduced or non-existent reproductive rate.
- ItemEXPOSIÇÃO A UMA DIETA COM ALTO TEOR DE CARBOIDRATOS REFINADOS LEVA A ANORMALIDADES METABÓLICAS E REPRODUTIVAS, SEMELHANTES A CARACTERÍSTICAS DA SÍNDROME DO OVÁRIO POLICÍSTICO E FALÊNCIA OVARIANA EM RATAS(Universidade Federal do Espírito Santo, 2022-01-17) Nino, Oscar Mauricio Santamaria; Graceli, Jones Bernardes; https://orcid.org/0000000193494369; http://lattes.cnpq.br/3803670746263603; https://orcid.org/; http://lattes.cnpq.br/; Alves, Leandro Miranda; https://orcid.org/; http://lattes.cnpq.br/; Santos, Roger Lyrio dos; https://orcid.org/; http://lattes.cnpq.br/1122196233280741; Lima, Leandro Ceotto Freitas; https://orcid.org/; http://lattes.cnpq.br/; Santos, Leonardo dos; http://lattes.cnpq.br/4132087001362623Obesity is associated with female reproductive complications, such as polycystic ovary syndrome (SOP), is linked with obesity and insulin resistance (IR). The exact mechanism of this relationship remains unclear. We identified a Few studies that used refi
- ItemO cloreto de tributilestanho desregula o eixo hipotalâmico-hipofisário-adrenal em diferentes níveis em ratas(Universidade Federal do Espírito Santo, 2017-09-12) Merlo, Eduardo; Lima, Leandro Ceotto Freitas; Graceli, Jones Bernardes; Stefanon, Ivanita; Alves, Leandro MirandaTributyltin chloride (TBT) is an environmental contaminant that is used as a biocide in antifouling paints. TBT has been shown to induce effects of endocrine disruption. However, studies evaluating the effects of TBT on the hypothalamic-pituitary-adrenal (HPA) axis are especially rare. The present study demonstrates that exposure to TBT is critically responsible for the inappropriate function of the mammalian HPA axis, as well as the development of abnormal morphology in the pituitary and adrenal gland. Female rats were treated with TBT and the HPA axis morphophysiology was evaluated. High CRH, low ACTH expression and high plasma corticosterone levels were detected in TBT rats. In addition, TBT increases the expression of the iNOS protein in the rat hypothalamus. Morphophysiological abnormalities, including inflammation, altered cellular redox balance, apoptosis and collagen deposition in the pituitary and adrenal glands, in addition to increased adiposity and PPARγ protein expression in the adrenal, were observed in TBT rats. Together, these data provide in vivo evidence that TBT leads to functional dissociation between CRH, ACTH and orticosterone, which could be associated with inflammation and increased iNOS expression in the hypothalamus. Thus, TBT exerts toxic effects at different levels on HPA axis function.
- ItemO obesogênico tributilestanho induz adipogênese anormal nos ovários de ratas adultas(Universidade Federal do Espírito Santo, 2018-04-27) Araújo, Julia Fernandez Puñal de; Lima, Leandro Ceotto Freitas; Graceli, Jones Bernardes; Santos, Roger Lyrio dos; Alves, Leandro MirandaTributyltin (TBT) is an obesogen associated with various metabolic and reproductive dysfunctions after in utero exposure. However, few studies have evaluated the obesogenic effect of TBT on adult ovaries. In this work, we evaluated the effects of this pollutant on the reproductive tract of adult female rats, as well as the obesogenic effect on these organs. For this, TBT was administered for 30 days in Wistar female rats at 12 weeks of age and with normal estrous cycle. During treatment, this cycle was followed, and we observed changes in phases and length. We also evaluated the biometric parameters and the morphology of the reproductive system, focusing on ovary and uterus. Were made dosages of sex hormones (LH, FSH, progesterone, estrogen and testosterone), noting that their levels were altered. In addition, it was observed that the steroidogenic pathway was altered in treated animals. We also evaluated the expression of proteins and mRNA of factors that regulate adipogenesis. These animals demonstrated abnormal ovarian adipogenesis with increased cholesterol levels, increased lipid accumulation and increased expression of PPARγ, C/EBP-β and Lipin-1. A negative correlation was observed between ovarian PPARγ expression and aromatase expression in TBT rats. In addition, exposure to TBT resulted in atrophy, inflammation, oxidative stress and fibrosis in the reproductive tract. Ovarian dysfunctions also occurred along with uterine irregularities and abnormal adipogenic ovary markers of TBT animals, may be associated with these uterine irregularities, as a positive correlation was observed between ovary cholesterol levels and uterine inflammation in TBT rats. These findings suggest that TBT leads to ovarian obesogenic effects directly by abnormal adipogenesis and/or indirectly through irregularities in the reproductive tract.
- ItemPotencial toxicológico do cádmio em dose semelhante à de exposição ocupacional na gênese de complicações no trato reprodutivo de ratas wistar(Universidade Federal do Espírito Santo, 2023-02-16) Costa, Charles Santos da; Graceli, Jones Bernardes; https://orcid.org/0000000193494369; http://lattes.cnpq.br/3803670746263603; https://orcid.org/0000-0003-3616-8211; http://lattes.cnpq.br/8647659013623563; Alves, Leandro Miranda; https://orcid.org/0000-0001-7832-8717; http://lattes.cnpq.br/9883547704448526; Padilha, Alessandra Simão; https://orcid.org/0000-0002-9585-1347; http://lattes.cnpq.br/7658998034219799; Santos, Roger Lyrio dos; https://orcid.org/0000-0003-4316-7196; http://lattes.cnpq.br/1122196233280741; Lima, Leandro Ceotto FreitasCadmium (Cd) is a toxic heavy metal known to be a major endocrine disruptor. However, few studies have explored the effects of Cd exposure on developing polycystic ovary syndrome (PCOS) features and premature ovarian failure (POF). In this study, we evaluated whether subacute exposure to Cd at a dose similar to that of occupational exposure results in damage to the hypothalamic-pituitarygonadal (HPG) axis and abnormalities related to PCOS and FOP. Wistar rats were exposed to CdCl₂ (100 ppm in water for 30 days), we evaluated the levels of Cd in the blood, HPG axis and uterus. In addition, we evaluated metabolic factors, HPG axis function, reproductive tract morphophysiology, inflammation, oxidative stress and fibrosis. Exposure to Cd raised its levels in serum, HPG axis and uterus. The Cd rats presented metabolic damage, adiposity reduction, dyslipidemia and insulin resistance (IR). Cd also caused the HPG axis to malfunction. Irregularities in the estrous cycle, abnormal hypothalamic mRNA expression with overexpression of Kisspeptin 1 (Kiss1), androgen receptor (AR) and rapamycin mechanistic target protein (mTOR) and lower expression of Kiss1 (Kiss1R) and leptin receptors (LepR) were observed and tumor necrosis factor alpha (TNF-a), high levels of luteinizing hormone (LH), low levels of anti-Müllerian hormone (AMH) and abnormal ovarian follicular development, reduced ovarian reserve and follicle number antral were observed, suggesting ovarian depletion. Furthermore, exposure to Cd decreases the granulosa layer thickness and the corpora lutea counting and increases the cystic and atretic follicles. Cd exposure increased inflammation, oxidative stress, and remodeling in the reproductive tract. Finally, positive correlations were observed between serum and reproductive tract Cd levels with insulin resistance, dyslipidemia and estrous cycle duration, cystic and atretic follicles, LH levels and inflammation. Thus, these data suggest that subacute exposure to Cd at a dose similar to that of occupational exposure alters the function of the HPG axis, leading to PCOS and FOP features besides metabolic abnormalities in female rats.
- ItemTributilestanho prejudica a morfofisiologia renal de ratas(Universidade Federal do Espírito Santo, 2016-05-13) Coutinho, João Victor da Silva; Gava, Ágata Lages; Graceli, Jones Bernardes; Santos, Roger Lyrio dos; Mendes, Leonardo; Alves, Leandro MirandaTributyltin chloride (TBT) is an organometallic pollutant that is used as a biocide in antifouling paints. TBT induces several toxic and endocrine-disrupting effects. However, studies evaluating the effects of TBT on renal function are rare. This study demonstrates that TBT exposure is responsible for improper renal function as well as the development of abnormal morphophysiology in mammalian kidneys. Female rats were treated with TBT, and their renal morphophysiology was assessed. Morphophysiological abnormalities such as decreased glomerular filtration rates and increased proteinuria levels were observed in TBT rats. In addition, increases in inflammation, collagen deposition and α-smooth muscle action (α-SMA) protein expression were observed in TBT rat kidneys. A disrupted cellular redox balance and apoptosis in kidney tissue were also observed in TBT rats. TBT rats demonstrated reduced serum estrogen levels and kidney estrogen receptor-α (ERα) protein expression. Together, these data provide in vivo evidence that TBT is toxic to normal renal function and that these effects may be associated with renal histopathology complications.