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1.
Br J Clin Pharmacol ; 87(3): 806-815, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32978831

RESUMO

AIMS: Beta-blockers are commonly used to treat hypertension that arises during pregnancy. However, reproductive safety concerns have been expressed. Here, we investigated whether the use of ß-blockers during early pregnancy increased the risk of congenital malformations. METHODS: A systematic literature search was performed in PubMed, Embase and Cochrane Library to identify relevant studies published from database inception until February 2020. Observational studies evaluating associations between maternal ß-blocker use and congenital malformations were included in this meta-analysis. Two reviewers independently extracted data and assessed study quality. Meta-analysis of outcomes was performed and a summary odds ratio (OR) was calculated with consideration of heterogeneity. RESULTS: Twenty observational studies were identified. Beta-blocker use during early pregnancy was not associated with an increased risk of congenital malformations (OR = 1.01, 95% confidence interval [CI] = 0.93-1.09). Subgroup analysis of organ-specific malformations revealed that ß-blocker use was associated with an increased risk of heart malformations (OR = 1.29, 95% CI = 1.02-1.63) and an increased risk of cleft lip or palate (OR = 1.5, 95% CI = 1.18-1.91); however, these associations (OR = 1.11, 95% CI = 0.94-1.32 for heart malformations; OR = 1.34, 95% CI = 0.98-1.85 for cleft lip or palate) disappeared when the adjusted data were pooled. Beta-blocker use was not associated with increased risks of central nervous system malformations, neural tube defects or hypospadias. CONCLUSION: Exposure to ß-blockers during early pregnancy does not appear to be associated with congenital malformations or heart malformations in offspring. Other organ-specific congenital malformations should be evaluated in further studies.


Assuntos
Cardiopatias Congênitas , Hipertensão , Antagonistas Adrenérgicos beta/efeitos adversos , Feminino , Cardiopatias Congênitas/induzido quimicamente , Cardiopatias Congênitas/epidemiologia , Humanos , Masculino , Estudos Observacionais como Assunto , Razão de Chances , Gravidez
2.
Horm Behav ; 105: 95-103, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30096284

RESUMO

Estrogen receptors (ERs) are thought to be associated with the onset and progression of neurodegenerative injuries and diseases, but the relationship and mechanisms underlying between ERs and cognition in type 1 diabetes remain elusive. In the current study, we investigated the effects of ERα and ERß on the memory impairment and apoptosis in streptozotocin-induced diabetic mice. We found that ERα and/or ERß activation using their agonists (0.5 mg/kg E2, PPT or DPN) ameliorate memory impairment in the Morris water maze (MWM) and Y-maze tests and suppress apoptosis as evidenced by decreased caspase-3 activity and increased ratio of Bcl-2/Bax. Importantly, treatment with the pharmacologic ERs agonists caused significant increases in the membrane ERα and ERß expression and subsequent PI3K/Akt, CREB and BDNF activation in the hippocampus of diabetic mice. Our data indicate that ERα and ERß are involved in the cognitive impairment of type 1 diabetes and that activation of ERs via administration of ERs agonists could be a novel and promising strategy for the treatment of diabetic cognitive impairment.


Assuntos
Disfunção Cognitiva/tratamento farmacológico , Diabetes Mellitus Experimental/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Disfunção Cognitiva/etiologia , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/psicologia , Estradiol/farmacologia , Estradiol/uso terapêutico , Receptor alfa de Estrogênio/agonistas , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/agonistas , Receptor beta de Estrogênio/metabolismo , Feminino , Hipocampo/efeitos dos fármacos , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Fármacos Neuroprotetores/farmacologia , Nitrilas/farmacologia , Nitrilas/uso terapêutico , Ovariectomia , Fenóis/farmacologia , Fenóis/uso terapêutico , Pirazóis/farmacologia , Pirazóis/uso terapêutico , Estreptozocina
3.
Antioxidants (Basel) ; 10(6)2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34071998

RESUMO

Oxidative stress has been suggested to negatively affect oocyte and embryo quality and developmental competence, resulting in failure to reach full term. In this study, we investigated the effect of N-acetyl-L-cysteine (NAC), a cell-permeating antioxidant, on developmental competence and the quality of oocytes and embryos upon supplementation (0.1-10 mM) in maturation and culture medium in vitro using slaughterhouse-derived oocytes and embryos. The results show that treating oocytes with 1.0 mM NAC for 8 h during in vitro maturation attenuated the intracellular reactive oxygen species (ROS) (p < 0.05) and upregulated intracellular glutathione levels (p < 0.01) in oocytes. Interestingly, we found that NAC affects early embryonic development, not only in a dose-dependent, but also in a stage-specific, manner. Significantly (p < 0.05) decreased cleavage rates (90.25% vs. 81.46%) were observed during the early stage (days 0-2), while significantly (p < 0.05) increased developmental rates (38.20% vs. 44.46%) were observed during the later stage (from day 3) of embryonic development. In particular, NAC supplementation decreased the proportion of apoptotic blastomeres significantly (p < 0.05), resulting in enhanced hatching capability and developmental rates during the in vitro culture of embryos. Taken together, our results suggest that NAC supplementation has beneficial effects on bovine oocytes and embryos through the prevention of apoptosis and the elimination of oxygen free radicals during maturation and culture in vitro.

4.
In Vitro Cell Dev Biol Anim ; 53(4): 344-353, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28127704

RESUMO

During mammalian embryo development in vitro, mechanism of embryonic development arrest caused by oxidative stress has not been clear so far. The tumor suppressor protein p53 controls cell cycle and programmed cell death by regulating relevant signal pathway. Recent researches revealed that the concentration and distribution of p53 are closely related with reactive oxygen species (ROS). The main objective of this experiment was to explore the role of p53 on embryonic development arrest caused by oxidative stress. Results showed that embryo arrest at two-four-cell stage was significantly increased in the presence of 50 µM H2O2 (39.01 ± 2.74 vs. 77.20 ± 5.34%, p < 0.05). Supplementation of N-acetyl-L-cysteine (NAC) obviously reduced the ratio of development arrest (39.01 ± 2.74 vs. 71.18 ± 5.34%, p < 0.05), which was accompanied by an increase in ROS level, and H2O2 treatment sharply increased messenger RNA (mRNA) expression and protein levels of p53 and p53-ser15. Further increased transcription of GADD45a and p21, a downstream of p53, has an especially significant effect on the mRNA expression of GADD45a. However, expressions of cdc2 were reduced by H2O2. In addition, using Pifithrin-α (PFT-α), the suppresser of p53, the result showed that GADD45a and p21 were significantly downregulated, but the cell cycle gene cdc2 was significantly upregulated, while the protein level of p53 and p53-ser15 was significantly decreased. Taken together, these results demonstrate that ROS could activate p53 and regulate p53 target genes to influence early embryo development in in vitro culture.


Assuntos
Desenvolvimento Embrionário/efeitos dos fármacos , Peróxido de Hidrogênio/toxicidade , Proteína Supressora de Tumor p53/metabolismo , Acetilcisteína/farmacologia , Animais , Benzotiazóis/farmacologia , Ciclo Celular/genética , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Embrião de Mamíferos/citologia , Feminino , Espaço Intracelular/metabolismo , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Serina/metabolismo , Tolueno/análogos & derivados , Tolueno/farmacologia , Zigoto/efeitos dos fármacos
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