Mestrado em Ciências Fisiológicas
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Navegando Mestrado em Ciências Fisiológicas por Autor "Alves, Leandro Miranda"
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- 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.
- 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.
- 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.