RESUMO
Systemic arterial hypertension (SAH) is one of the most prevalent chronic diseases worldwide and is related to serious health complications. It has been pointed out as a major risk factor for COVID-19. This study aimed to determine the impact of COVID-19 on the metabolomic profile, the correlation with the plasmatic levels of losartan and its active metabolite (EXP3174), biochemical markers, and blood pressure (BP) control in hypertensive patients. 1H NMR metabolomic profiles of hypertensive and normotensive patients with and without previous COVID-19 diagnosis were identified. Plasmatic levels of LOS and EXP3174 were correlated with BP, biochemical markers, and the metabolomic fingerprint of the groups. Biomarkers linked to important aspects of SAH and COVID-19 were identified, such as glucose, glutamine, arginine, creatinine, alanine, choline, erythritol, homogentisate, 0-tyrosine, and 2-hydroxybutyrate. Those metabolites are indicative of metabolic alterations, kidney damage, pulmonary dysfunction, and persistent inflammation, which can be found in both diseases. Some hypertensive patients did not reach the therapeutic levels of LOS and EXP3174, while the BP control was also limited among the normotensive patients with previous COVID-19 diagnoses. Metabolomics proved to be an important tool for assessing the effectiveness of losartan pharmacotherapy and the damage caused by SAH and COVID-19 in hypertensive patients.
RESUMO
Systemic arterial hypertension (SAH) is one of the most prevalent chronic diseases worldwide and, when dysregulated, may cause serious complications. Losartan (LOS) blocks relevant physiological aspects of hypertension, acting mainly on the reduction of peripheral vascular resistance. Complications of hypertension include nephropathy, in which diagnosis is based on the observation of functional or structural renal dysfunction. Therefore, blood pressure control is essential to attenuate the progression of chronic kidney disease (CKD). In this study, 1H NMR metabolomics were used to differentiate hypertensive and chronic renal patients. Plasmatic levels of LOS and EXP3174, obtained by liquid chromatography coupled with mass-mass spectroscopy, were correlated with blood pressure control, biochemical markers and the metabolomic fingerprint of the groups. Some biomarkers have been correlated with key aspects of hypertension and CKD progression. For instance, higher levels of trigonelline, urea and fumaric acid were found as characteristic markers of kidney failure. In the hypertensive group, the urea levels found could indicate the onset of kidney damage when associated with uncontrolled blood pressure. In this sense, the results point to a new approach to identify CKD in early stages and may contribute to improving pharmacotherapy and reducing morbidity and mortality associated with hypertension and CKD.
Assuntos
Hipertensão , Insuficiência Renal Crônica , Humanos , Losartan/uso terapêutico , Losartan/farmacologia , Pressão Sanguínea , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/farmacologia , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/complicações , Ureia/farmacologiaRESUMO
Anacardic acid extracted from cashew nut shells of Anacardium occidentale L has demonstrated important biological activities, such as antibacterial activity against the cariogenic specie Streptococcus mutans. Zein nanoparticles containing anacardic acid (9.375 µg/mL) were evaluated in terms of toxicity and genotoxicity in vivo. The subacute toxicity assay was used to evaluate the cumulative effects of the oral administration of nanoencapsulated anacardic acid at 2.25 and 112.5 µg/kg for 7 days in mice, simulating a mouth rinse short-term clinical course treatment. Blank zein nanoparticles and saline solution 0.9 % were used as negative controls. Peripheral blood samples were collected to evaluate the genotoxicity in polychromatic erythrocytes using the micronucleus test. The animals were anesthetized, euthanized and the target organs collected, weighed and submitted to histopathological analysis. Liver, kidney and spleen relative weights did not change. Nevertheless, stomach, lung and heart increased the relative weights in the group receiving the highest dose, in which occasional histopathological findings were also identified. Both doses maintained the micronucleus frequency within the normal range and the animals treated with the highest dose presented a discrete weight lost, which could explain the organs' relative weight reductions. Blank and anacardic acid loaded zein nanoparticles were nontoxic when administered repeatedly for 7 days, as no relevant histopathological changes neither genotoxicity were observed. These preparations demonstrated limited toxicity under the conditions used in this study and could become an antibacterial alternative for preventing/treating oral infections in short-term treatments.
RESUMO
Ellagic acid (EA) has demonstrated several biological properties, such as antioxidant, antimicrobial, and enzymatic inhibition. Zein and chitosan (CHI) are natural polymers whose biological potential has also gained attention. Therefore, this paper aimed to evaluate the antimicrobial, antioxidant, anticollagenase, and antielastase properties of EA, zein, and chitosan isolated or in combination. The microdilution method was used to assess the minimum inhibitory and bactericide concentrations. The antioxidant activity was determined using the 2,2-diphenyl-1-picryl-hydrazila free radical scavenging method. The anticollagenase and antielastase activities were evaluated by specific colorimetric tests. EA has shown inhibitory activity against Staphylococcus aureus and Pseudomonas aeruginosa together with an antioxidant IC50 of 0.079 mg/mL. EA also showed significant collagenase and elastase inhibition. Zein has shown antimicrobial and antioxidant activities itself and enhanced sinergically the antioxidant activity and the antimicrobial activity against P. aeruginosa when combined with EA. CHI increased sinergically the inhibitory activity of EA against both bacterial strains, while showed itself an acceptable antimicrobial activity. 1 H saturation transfer-difference nuclear magnetic resonance experiment confirmed the formation of a complex between EA and zein that could be related with the improvement on its biological performance over the individual compounds, while no chemical interaction was detected between CHI and EA. PRACTICAL APPLICATION: The results reinforce the potential of ellagic acid in combination with zein and/or chitosan as an antimicrobial, antienzimatic, and antioxidant agent. Those findings reinforce the use of these substances, protecting this bioactive from degradation and/or improving the functional characteristics and biopharmaceutical properties.
Assuntos
Quitosana/farmacologia , Ácido Elágico/farmacologia , Zeína/farmacologia , Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Colagenases/metabolismo , Inibidores Enzimáticos/farmacologia , Espectroscopia de Ressonância Magnética , Inibidores de Metaloproteinases de Matriz/farmacologia , Testes de Sensibilidade Microbiana , Elastase Pancreática/antagonistas & inibidores , Elastase Pancreática/metabolismo , Extratos Vegetais/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacosRESUMO
Zein is a protein containing a large amount of nonpolar amino acids, which has shown the ability to form aggregates and entrap solutes, such as drugs and amino acids. NMR techniques were used to detect binding interactions and measure affinity between zein and three different drugs: tetracycline, amoxicillin and indomethacin. The release study of zein microparticle formulations containing any of these drugs was confronted with the affinity results, showing a remarkable correlation. The feasible methodology employed, focused in the functionality of the protein-drug interaction, can be very promising for the rational design of appropriate drug vehicles for drug delivery.
Assuntos
Amoxicilina/química , Portadores de Fármacos/química , Indometacina/química , Tetraciclina/química , Zeína/química , Amoxicilina/metabolismo , Portadores de Fármacos/metabolismo , Indometacina/metabolismo , Ácido Láctico/química , Espectroscopia de Ressonância Magnética , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Ligação Proteica , Tetraciclina/metabolismo , Zeína/metabolismoRESUMO
The intracellularly-occurring Cu(I)-glutathione complex (Cu(I)-[GSH](2)) has the ability to reduce molecular oxygen into superoxide. Removal of such radicals leads to the irreversible conversion of Cu(I)-[GSH](2) into the redox-inactive Cu(II)-GSSG complex. The present study addressed the potential of reduced glutathione, ascorbate and superoxide to reductively regenerate Cu(I)-[GSH](2) from Cu(II)-GSSG, and investigated the redox changes involved in such process. Results show that: (i) among the three tested reductants, only GSH is able to reduce the Cu(II) bound to GSSG; (ii) during the reduction of Cu(II)-GSSG, a Cu(I)-GSSG intermediate would be formed (supported here by Cu(I) and GSSG recovery data and by NMR studies); (iii) when GSH is present in a molar excess equal or greater than 1:3, the reduction of Cu(II)-GSSG into Cu(I)-[GSH](2) is quantitative and complete. Under such conditions, the Cu(II)-GSSG complex acquires a superoxide-generating capacity which is identical to that seen with the Cu(I)-[GSH](2) complex. Within cells, the concentrations of GSH are at least 2- to 3-fold order of magnitude higher than those expected for the Cu(II)-GSSG complex. Thus, we postulate that the interaction between GSH and Cu(II)-GSSG could be seen as a potential mechanism to regenerate continuously the Cu(I)-[GSH](2) complex and thereby affect the ability of the latter to generate superoxide.