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1.
J Neurosci Res ; 96(1): 138-150, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28609588

RESUMO

Diabetic encephalopathy (DE), one of the most prevalent chronic complications of diabetes mellitus, is short of effective prevention and formidable therapeutic strategies. The aim of the present study is to reveal the imbalance of tryptophan (Trp) and its metabolites in streptozotocin (STZ)-induced experimental DE rats to underscore their critical values in clinical diagnosis of the disease. For this purpose, we first developed an accurate and appropriate simultaneous method for measuring Trp and its metabolites using liquid chromatography-tandem mass spectrometry, which was in accordance with the requirements of biological sample analysis. Secondly, a single STZ intraperitoneal injection was administered to male Sprague-Dawley rats, and their cognitive function was detected by Morris water maze tests. Cerebrospinal fluid (CSF), serum, and brain tissue were then collected for the determination of Trp and its metabolites. Compared with age-matched control rats, the levels of neuroprotective serotonin decreased significantly in the samples of cortices, hippocampi, striatum, CSF, and serums in the STZ-induced DE rats, while the levels of neurotoxic 3-hydroxykynurenine increased significantly. Moreover, analogous changes of both compounds were found in the central nervous system and peripheral blood of the STZ-induced DE rats. In conclusion, we established a quantitative method for the simultaneous detection of Trp and its metabolites, and we also present a critical elucidation of the nervous system dysfunction in DE.


Assuntos
Encefalopatias/metabolismo , Encéfalo/metabolismo , Diabetes Mellitus Experimental/metabolismo , Neurotransmissores/metabolismo , Triptofano/metabolismo , Animais , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Biomarcadores/metabolismo , Encéfalo/patologia , Encefalopatias/patologia , Diabetes Mellitus Experimental/patologia , Masculino , Neurotransmissores/análise , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem/métodos , Triptofano/análise
2.
J Pharm Sci ; 106(8): 2152-2162, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28479355

RESUMO

The progression of breast cancer is closely related to the levels of estrogens within the body. UDP-glucuronosyltransferase (UGT) is an important class of phase II metabolizing enzymes, playing a pivotal role in detoxifying steroid hormone. In the present study, we aim at uncovering the potential dysregulation pattern of UGT and its role in estrogen metabolism and in the pathogenesis of breast cancer. Female Sprague-Dawley rats were treated with 100 mg/kg dimethylbenz(a)anthracene (DMBA) to induce breast cancer. Our results showed that the expression and activity of UGT in mammary tissues were downregulated significantly in DMBA rats. Consistent with this, levels of estradiol, 4-hydroxylated estradiol, and 2-hydroxylated estradiol were increased in both mammary tissues and serum, supporting a notable accumulation of toxic estrogen species in the target tissue of breast cancer. In addition, we also observed the decreased cell migration, cell proliferation, and DNA damage in UGT-transfected MCF-7 cells, suggesting a protective role of UGT against estrogen-induced mammary carcinogenesis. Taken together, these results indicated that accumulation of estrogens induced by UGT deficiency is a critical factor to induce the development of breast cancer. UGT contributes to estrogen elimination, and its glucuronidation capacity influences the estrogen signaling pathway and the pathogenesis of breast cancer.


Assuntos
Neoplasias da Mama/metabolismo , Mama/metabolismo , Estrogênios/metabolismo , Glucuronosiltransferase/metabolismo , Animais , Mama/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Regulação para Baixo , Estradiol/análise , Estradiol/metabolismo , Estrogênios/análise , Feminino , Regulação Neoplásica da Expressão Gênica , Glucuronosiltransferase/genética , Humanos , Células MCF-7 , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Ratos , Ratos Sprague-Dawley
3.
J Chromatogr Sci ; 55(8): 839-845, 2017 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-28505281

RESUMO

A new type of partially substituted 3,5-dimethylphenylcarbamate-(3-(2-O-ß-cyclodextrin)-2-hydroxypropoxy)-propylsilyl-appended silica particles (MP-CD-HPS) have been prepared by a convenient post-immobilization derivazition procedure. The MP-CD-HPS has been successfully used as chiral stationary phase (CSP) for high-performance liquid chromatography (HPLC) under normal phase, reversed phase and polar organic mobile phase conditions. The chromatographic evaluation results show that the MP-CD-HPS has excellent selectivity for the separation of aromatic positional isomers and enantiomers of some chiral compounds. The multi-mode HPLC separation results also indicate that both the stable ether spacer linking to the wider torus rim of ß-cyclodextrin in the MP-CD-HPS phase and the hydroxyl residues in the partially substituted ß-cyclodextrin have important contributions to chiral recognitions and chromatographic separations.

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