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2.
Biol Trace Elem Res ; 202(1): 246-257, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37086356

RESUMO

This study is based on the premise that the application of chemical synthesis strategies to structurally modify commercial drugs by complexation with biometals is a valid procedure to improve their biological effects. Our purpose is to synthesize a compound with greater efficacy than the original drug, able to enhance its antihypertensive and cardiac pharmacological activity. Herein, the structure of the coordination compound of Zn(II) and the antihypertensive drug olmesartan, [Zn(Olme)(H2O)2] (ZnOlme), is presented. After 8 weeks of treatment in SHR male rats, ZnOlme displayed a better blood pressure-lowering activity compared with olmesartan, with a noticeable effect even in the first weeks of treatment, while ZnCl2 showed similar results than the control. ZnOlme also reduced left ventricle (LV) weight and left ventricle/tibia length ratio (LV/TL), posterior wall thickness (PWT), and intraventricular septum in diastole (IVSd) suggesting its potential to prevent LV hypertrophy. Besides, ZnOlme reduced interstitial fibrosis (contents of collagen types I and III, responsible for giving rigidity and promoting vascular elasticity, respectively). The recovery of heart function was also evidenced by fractional shortening (diastolic left ventricular/systolic left ventricular) diameter determinations. Furthermore, ZnOlme increased the antioxidant capacity and prevented cardiac oxidative stress: it enhanced the reduction of reactive oxygen species generation, exerted a significant decrease in lipid peroxidation and enhanced glutathione contents in heart tissues compared to the control, Zn, and olmesartan treatments. Our results demonstrate that continuous oral administration of ZnOlme causes a better antihypertensive effect and grants enhancement of cardioprotection through antioxidant activity, in combination with hemodynamic improvement.


Assuntos
Anti-Hipertensivos , Hipertensão , Ratos , Animais , Masculino , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Ratos Endogâmicos SHR , Pressão Sanguínea , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Hipertrofia Ventricular Esquerda/prevenção & controle , Zinco/farmacologia , Zinco/uso terapêutico
3.
J Trace Elem Med Biol ; 81: 127327, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37890445

RESUMO

BACKGROUND: the antihypertensive drug α-methyldopa (MD) stands as one of the extensively used medications for managing hypertension during pregnancy. Zinc deprivation has been associated with many diseases. In this context, the synthesis of a Zn coordination complex [Zn(MD)(OH)(H2O)2]·H2O (ZnMD) provide a promising alternative pathway to improve the biological properties of MD. METHODS: ZnMD was synthesized and physicochemically characterized. Fluorescence spectral studies were conducted to examine the binding of both, the ligand and the metal with bovine serum albumin (BSA). MD, ZnMD, and ZnCl2 were administered to spontaneous hypertensive rats (SHR) rats during 8 weeks and blood pressure and echocardiographic parameters were determined. Ex vivo assays were conducted to evaluate levels of reactive oxygen species (ROS), thiobarbituric acid reactive substances (TBARS), and nitric oxide (NO). Cross-sectional area (CSA) and collagen levels of left ventricular cardiomyocytes were also assessed. Furthermore, the expression of NAD(P)H oxidase subunits (gp91phox and p47phox) and Superoxide Dismutase 1 (SOD1) was quantified through western blot analysis. RESULTS: The complex exhibited a moderate affinity for binding with BSA showing a spontaneous interaction (indicated by negative ΔG values) and moderate affinity (determined by affinity constant values). The binding process involved the formation of Van der Waals forces and hydrogen bonds. Upon treatment with MD and ZnMD, a reduction in the systolic blood pressure in SHR was observed, being ZnMD more effective than MD (122 ± 8.1 mmHg and 145 ± 5.6 mmHg, at 8th week of treatment, respectively). The ZnMD treatment prevented myocardial hypertrophy, improved the heart function and reduced the cardiac fibrosis, as evidenced by parameters such as left ventricular mass, fractional shortening, and histological studies. In contrast, MD did not show noticeable differences in these parameters. ZnMD regulates negatively the oxidative damage by reducing levels of ROS and lipid peroxidation, as well as the cardiac NAD(P)H oxidase, and increasing SOD1 expression, while MD did not show significant effect. Moreover, cardiac nitric oxide levels were greater in the ZnMD therapy compared to MD treatment. CONCLUSION: Both MD and ZnMD have the potential to be transported by albumin. Our findings provide important evidence suggesting that this complex could be a potential therapeutic drug for the treatment of hypertension and cardiac hypertrophy and dysfunction.


Assuntos
Anti-Hipertensivos , Hipertensão , Ratos , Animais , Anti-Hipertensivos/uso terapêutico , Metildopa/farmacologia , Metildopa/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase-1 , Óxido Nítrico/metabolismo , Hipertensão/tratamento farmacológico , Pressão Sanguínea , Ratos Endogâmicos SHR , Miócitos Cardíacos/metabolismo , Cardiomegalia , NADPH Oxidases , Zinco/farmacologia , Zinco/uso terapêutico
5.
Diagn. tratamento ; 27(2): 55-60, abr-jun. 2022. ilus, tab, tab
Artigo em Português | LILACS | ID: biblio-1369114

RESUMO

Contexto: O zinco é um elemento-traço que age no sistema auditivo, atuando em sinapses auditivas e na cóclea, sobretudo junto à enzima superóxido dismutase. Objetivo: Avaliar a efetividade da suplementação de zinco para o tratamento de cocleovestibulopatias. Material e Métodos: Trata-se de sinopse baseada em evidências. Procedeu-se à busca por estudos que associavam zinco à perda auditiva, tontura e zumbido em três bases eletrônicas de dados: Cochrane - Central de Registros de Ensaios Clínicos - CENTRAL (2022), PubMed (1966- 2022) e Portal BVS (1982-2022). Dois pesquisadores independentemente extraíram os dados e avaliaram a qualidade dos estudos para a síntese. Os desfechos de análise envolveram melhora de perda auditiva, tontura e zumbido. Resultados: Foram encontrados 231 estudos. Cinco estudos (quatro ensaios clínicos randomizados e uma revisão sistemática) envolvendo um total de 249 pacientes. Discussão: A literatura mundial apresenta poucos estudos relacionando zinco e cocleovestibulopatias. A maioria trata-se de estudos in vitro ou de experimentação animal. Os estudos em humanos são ensaios clínicos de baixa amostragem e elevada heterogeneidade, que avaliaram melhora de perda auditiva e melhora de zumbido. Nenhum estudo avaliou melhora da tontura. O nível de evidência é muito baixo e não permite, nesse momento, aferir a efetividade do zinco para tratamento de cocleovestibulopatias em humanos, sendo sua utilização clínica baseada na experiência de cada profissional. Conclusões: Não há evidência de efetividade da suplementação de zinco no tratamento de cocleovestibulopatias, sendo recomendada a realização de novos estudos de boa qualidade metodológica. PALAVRAS-CHAVE: Zinco, perda auditiva, tontura, zumbido, prática clínica baseada em evidências


Assuntos
Humanos , Zumbido , Zinco/uso terapêutico , Suplementos Nutricionais , Tontura/tratamento farmacológico , Prática Clínica Baseada em Evidências , Perda Auditiva/prevenção & controle
6.
Nutr Rev ; 80(5): 1086-1093, 2022 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-34338769

RESUMO

Zinc supplementation is indicated for diarrhea and taste disorders, which are both features of COVID-19 . Nevertheless, this strategy has not been tested for the treatment of these secondary complications in the current pandemic. Through an updated review, a practical appraisal was considered as a means of providing a medical nexus of therapeutic zinc regimens as an adjunct in the management of COVID-19-related diarrhea and ageusia/dysgeusia. While diarrhea and taste disorders are consequences of COVID-19, zinc supplementation is useful for non-COVID-19 patients with these clinical problems. The overwhelming evidence for supplementing with zinc in diarrhea and pneumonia is associated with the treatment of children, while for taste disorders the use of supplementing with zinc is more examined in adults. Whereas COVID-19 is more prevalent in adults, precautions should be exercised not to translate the zinc dosage used for children with diarrhea and taste disorders into the current pandemic. Therapeutic doses of zinc used for adults (∼50-150 mg/day of elemental zinc) could be included in the treatment strategies for COVID-19, but this proposal should be examined through randomized studies.


Assuntos
Ageusia , Tratamento Farmacológico da COVID-19 , Adulto , Ageusia/complicações , Ageusia/tratamento farmacológico , Criança , Diarreia/tratamento farmacológico , Suplementos Nutricionais , Disgeusia/tratamento farmacológico , Disgeusia/etiologia , Humanos , Distúrbios do Paladar/complicações , Distúrbios do Paladar/tratamento farmacológico , Zinco/uso terapêutico
7.
Br J Nutr ; 127(8): 1172-1179, 2022 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-34128459

RESUMO

Zn deficiency compromises its biological functions, its effect on the immune system and its antiviral activity, increasing vulnerability to infectious diseases. This narrative review aims at presenting and discussing functional aspects and possible mechanisms involved in the potential role of Zn in the immune response and antiviral activity for coronavirus infectious disease-19 (COVID-19) prevention and control. The searches were conducted in PubMed and Science Direct databases, using clinical trials, experimental studies in animals and humans, case-control studies, case series, letters to the editor, and review articles published in English, without restrictions on year of publication. Search approach was based on using the terms: 'zinc', 'COVID-19', 'antiviral agents', 'immunologic factors' and 'respiratory tract infections'. Literature shows the importance of Zn as an essential mineral immunomodulator with relevant antiviral activity in the body. Thus, although there is still a scarcity of studies evaluating Zn supplementation in patients with COVID-19, the results on the topic show the necessity of controlling Zn mineral deficiency, as well as maintaining its homoeostasis in the body in order to strengthen the immune system and improve the prevention of highly complex viral infections, such as that of the COVID-19.


Assuntos
Tratamento Farmacológico da COVID-19 , Doenças Transmissíveis , Viroses , Antivirais/farmacologia , Antivirais/uso terapêutico , Doenças Transmissíveis/tratamento farmacológico , Humanos , Zinco/uso terapêutico
8.
Rev. ANACEM (Impresa) ; 16(2): 95-100, 2022. ilus
Artigo em Espanhol | LILACS | ID: biblio-1525875

RESUMO

El Trastorno por Déficit de Atención con Hiperactividad (TDAH) es un trastorno del comportamiento común en la infancia, caracterizado por la presencia de hiperactividad, impulsividad, problemas de atención y dificultades en las interacciones sociales. El objetivo de esta revisión bibliográfica fue identificar los tratamientos disponibles para el manejo del TDAH, tanto farmacológicos como no farmacológicos. La búsqueda se realizó en PubMed y Google Scholar, recopilando 285 artículos. Se excluyeron aquellos que no estaban en inglés o español, incluían población adulta o no se ajustaban al propósito de la revisión. Se seleccionaron 48 artículos y se incluyeron finalmente 30 para la lectura. Se concluye que la evidencia sugiere un enfoque combinado de tratamiento farmacológico y no farmacológico. Entre los tratamientos farmacológicos, los estimulantes como el metilfenidato siguen siendo la opción de primera línea. Además, hay estudios preliminares que respaldan la suplementación de hierro, vitamina D, zinc, omega 3, ginseng rojo y proteína de suero de leche. En cuanto a los tratamientos no farmacológicos, hay una amplia variedad de estrategias terapéuticas, como psicoeducación, entrenamiento en habilidades sociales, terapia de aceptación y compromiso, entrenamiento para padres, neurofeedback, aplicaciones de juegos móviles, actividad física, higiene del sueño, estimulación magnética transcraneal, acupuntura y terapia asistida por caballos. Aunque estos estudios son prometedores, muchos son incipientes, y se requiere más investigación en este campo.


Attention Deficit Hyperactivity Disorder (ADHD) is a common behavioral disorder in childhood, characterized by the presence of hyperactivity and impulsivity, attention problems, and difficulties in social interactions. The objective of this bibliographic review was to identify the available treatments for the non-pharmacological and pharmacological management of ADHD. A search was conducted in PubMed for articles published in the last 5 years and in Google Scholar since 2018, resulting in 285 collected articles. Articles not in English or Spanish, including adults in their population, or not fitting the purpose of this review were excluded. Out of 48 selected articles for reading, 30 were finally included. The available evidence suggests a combined approach of pharmacological and non-pharmacological treatment. Stimulants such as methylphenidate continue to be the first-line treatment among pharmacological measures. Incipient studies recommend the use of iron, vitamin D, zinc, omega 3, red ginseng, and whey protein supplementation. Non-pharmacological measures include a variety of therapeutic strategies, such as psychoeducation, training in social skills, acceptance and commitment therapy, training for parents, neurofeedback, mobile game applications, physical activity, sleep hygiene, transcranial magnetic stimulation, acupuncture, and horse-assisted therapy. While these studies show promise, most are still in the early stages, emphasizing the need for further research in this area.


Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/terapia , Terapias Complementares/métodos , Zinco/uso terapêutico , Ferro/uso terapêutico , Metilfenidato/uso terapêutico
9.
Ann Hepatol ; 25: 100549, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34614431

RESUMO

Malnutrition among patients with chronic liver disease (CLD) is a common complication with significant prognostic implications for patients with liver cirrhosis. Micronutrient deficiency has been associated with an increased risk of hepatic decompensation and is an independent risk factor for mortality among cirrhotic patients. Micronutrient deficiencies in patients with CLD include zinc, vitamin A, vitamin D and selenium. This review article aims to evaluate the literature to date on the complications of zinc deficiency in patients with CLD. A management algorithm for zinc replacement has also been proposed.


Assuntos
Suplementos Nutricionais , Hepatopatias/terapia , Oligoelementos/uso terapêutico , Zinco/uso terapêutico , Doença Crônica , Humanos , Hepatopatias/diagnóstico , Hepatopatias/etiologia
10.
Oxid Med Cell Longev ; 2021: 6696538, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34040692

RESUMO

Oxygen deprivation in newborns leads to hypoxic-ischemic encephalopathy, whose hallmarks are oxidative/nitrosative stress, energetic metabolism alterations, nutrient deficiency, and motor behavior disability. Zinc and taurine are known to protect against hypoxic-ischemic brain damage in adults and neonates. However, the combined effect of prophylactic zinc administration and therapeutic taurine treatment on intrauterine ischemia- (IUI-) induced cerebral damage remains unknown. The present work evaluated this issue in male pups subjected to transient IUI (10 min) at E17 and whose mothers received zinc from E1 to E16 and taurine from E17 to postnatal day 15 (PND15) via drinking water. We assessed motor alterations, nitrosative stress, lipid peroxidation, and the antioxidant system comprised of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Enzymes of neuronal energetic pathways, such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH), were also evaluated. The hierarchization score of the protective effect of pharmacological strategies (HSPEPS) was used to select the most effective treatment. Compared with the IUI group, zinc, alone or combined with taurine, improved motor behavior and reduced nitrosative stress by increasing SOD, CAT, and GPx activities and decreasing the GSSG/GSH ratio in the cerebral cortex and hippocampus. Taurine alone increased the AST/ALT, LDH/ALT, and AST/LDH ratios in the cerebral cortex, showing improvement of the neural bioenergetics system. This result suggests that taurine improves pyruvate, lactate, and glutamate metabolism, thus decreasing IUI-caused cerebral damage and relieving motor behavior impairment. Our results showed that taurine alone or in combination with zinc provides neuroprotection in the IUI rat model.


Assuntos
Glutationa Peroxidase/metabolismo , Isquemia/tratamento farmacológico , Taurina/metabolismo , Zinco/uso terapêutico , Animais , Masculino , Ratos , Zinco/farmacologia
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