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1.
Biosensors (Basel) ; 11(9)2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34562929

RESUMO

The gut microbiota plays a critical role in chronic kidney disease (CKD) and hypertension. Trimethylamine-N-oxide (TMAO) and trimethylamine (TMA) are gut microbiota-derived metabolites, and both are known uraemic toxins that are implicated in CKD, atherosclerosis, colorectal cancer and cardiovascular risk. Therefore, the detection and quantification of TMAO, which is a metabolite from gut microbes, are important for the diagnosis of diseases such as atherosclerosis, thrombosis and colorectal cancer. In this study, a new "colour-switch" method that is based on the combination of a plasma separation pad/absorption pad and polyallylamine hydrochloride-capped manganese dioxide (PAH@MnO2) nanozyme was developed for the direct quantitative detection of TMAO in whole blood without blood sample pretreatment. As a proof of concept, a limit of quantitation (LOQ) of less than 6.7 µM for TMAO was obtained with a wide linear quantification range from 15.6 to 500 µM through quantitative analysis, thereby suggesting potential clinical applications in blood TMAO monitoring for CKD patients.

2.
Nutrients ; 13(9)2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34578924

RESUMO

Maternal exposure to environmental pollutants affects fetal development, which can result in hypertension in adulthood. Gut microbiota-derived metabolite trimethylamine (TMA), trimethylamine-N-oxide (TMAO), and short chain fatty acids (SCFAs) have been associated with hypertension. We tested a hypothesis that maternal 3,3-Dimethyl-1-butanol (DMB, a TMA inhibitor) therapy prevents 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure-induced hypertension in adult offspring relevant to alterations of gut microbiota-derived metabolites, the mediation of aryl hydrocarbon receptor (AHR) signaling, and the renin-angiotensin system (RAS). Pregnant Sprague-Dawley rats were given weekly oral dose of TCDD 200 ng/kg for four doses (T), 1% DMB in drinking water (D), TCDD + DMB (TD), or vehicle (C) in pregnancy and lactation periods. Male progeny (n = 8/group) were sacrificed at the age of 12 weeks. Perinatal TCDD exposure caused hypertension in adult male offspring coinciding with reduced α-diversity, increased the Firmicutes to Bacteroidetes ratio, less abundant beneficial bacteria, impaired SCFA receptors' expression, the activation of AHR signaling, and the aberrant activation of the RAS. Treatment with DMB during pregnancy and lactation rescued hypertension induced by perinatal TCDD exposure. This was accompanied by reshaping gut microbiota, mediating TMA-TMAO metabolic pathway, increasing acetic acid and its receptors, and restoring the AHR and RAS pathway. Our data provide new insights into the therapeutic potential of DMB, a microbiome-based metabolite treatment, for the prevention of hypertension of developmental origins.

3.
Nutrients ; 13(9)2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34579143

RESUMO

Recent studies demonstrated that metabolic syndrome and cardiovascular diseases could be elicited by developmental programming, which is regulated by prenatal nutritional and environmental stress. In this study, we utilized a rat model to examine the effect of excessive maternal fructose intake during pregnancy and lactation on cardiac development and progression of pressure overload-induced cardiac hypertrophy in offspring. Transverse aortic constriction (TAC) was performed on 3-month-old male offspring to induce ventricular pressure overload. Four weeks post-TAC, echocardiographic assessment as well as histopathological and biochemical examinations were performed on the myocardium of the offspring. Echocardiographic and gross examinations showed that heart weight, interventricular septal thickness in diastole (IVD; d), and left ventricular posterior wall thickness in diastole (LVPW; d) were elevated in offspring with TAC and further increased by maternal fructose exposure (MFE). However, the left ventricular ejection function was not significantly affected. Myocardial histopathological examination revealed that the indices of fibrosis and oxidative stress were higher in offspring with MFE and TAC than those in animals receiving either treatment. Molecular examinations on the myocardium demonstrated an MFE-induced upregulation of p38-MAPK signaling. Next generation sequence (NGS) analysis indicated a modulation of the expression levels of several cardiac hypertrophy-associated genes, including GPR22, Myh7, Nppa, P2RX4, and Npy by MFE. Subsequent RT-PCR indicated that MFE regulated the expression levels of genes responsive to cardiac hypertrophy (i.e., Myh-7, ANP) and oxidative stress (i.e., GR, GPx, and NQO-1). In conclusion, MFE during pregnancy and lactation modulated myocardial gene expression, increased oxidative stress, and exacerbated ventricular pressure overload-induced cardiac remodeling in rat offspring.

4.
Lipids Health Dis ; 20(1): 100, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34496884

RESUMO

BACKGROUND: The deleterious effect of maternal high-fat diet (HFD) on the fetal rat liver may cause later development of non-alcoholic fatty liver disease (NAFLD). The aim of this study was to evaluate the effect of maternal HFD-induced maternal hepatic steatosis and dysbiosis on the fetal liver and intestines, and the effect of prenatal metformin in a rat model. METHODS: Sprague-Dawley rats were assigned to three groups (N = 6 in each group). Before mating, the rats were randomly assigned to HFD or normal-chow diet (NCD) group for 7 weeks. After mating, the HFD group rats were continued with high-fat diet during pregnancy and some of the HFD group rats were co-treated with metformin (HFMf) via drinking water during pregnancy. All maternal rats and their fetuses were sacrificed on gestational day 21. The liver and intestinal tissues of both maternal and fetal rats were analyzed. In addition, microbial deoxyribonucleic acid extracted from the maternal fecal samples was analyzed. RESULTS: HFD resulted in maternal weight gain during pregnancy, intrahepatic lipid accumulation, and change in the serum short-chain fatty acid profile, intestinal tight junctions, and dysbiosis in maternal rats. The effect of HFD on maternal rats was alleviated by prenatal metformin, which also ameliorated inflammation and apoptosis in the fetal liver and intestines. CONCLUSIONS: This study demonstrated the beneficial effects of prenatal metformin on maternal liver steatosis, focusing on the gut-liver axis. In addition, the present study indicates that prenatal metformin could ameliorate maternal HFD-induced inflammation and apoptosis in the fetal liver and intestines. This beneficial effect of in-utero exposure of metformin on fetal liver and intestines has not been reported. This study supports the use of prenatal metformin for pregnant obese women.

5.
Nutrients ; 13(7)2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34371800

RESUMO

Cardiovascular diseases (CVDs) can originate from early life. Accumulating evidence suggests that gut microbiota in early life is linked to CVDs in later life. Gut microbiota-targeted therapy has gained significant importance in recent decades for its health-promoting role in the prevention (rather than just treatment) of CVDs. Thus far, available gut microbiota-based treatment modalities used as reprogramming interventions include probiotics, prebiotics, and postbiotics. The purpose of this review is, first, to highlight current studies that link dysbiotic gut microbiota to the developmental origins of CVD. This is followed by a summary of the connections between the gut microbiota and CVD behind cardiovascular programming, such as short chain fatty acids (SCFAs) and their receptors, trimethylamine-N-oxide (TMAO), uremic toxins, and aryl hydrocarbon receptor (AhR), and the renin-angiotensin system (RAS). This review also presents an overview of how gut microbiota-targeted reprogramming interventions can prevent the developmental origins of CVD from animal studies. Overall, this review reveals that recent advances in gut microbiota-targeted therapy might provide the answers to reduce the global burden of CVDs. Still, additional studies will be needed to put research findings into practice.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Disbiose/prevenção & controle , Microbioma Gastrointestinal/fisiologia , Terapia Nutricional/métodos , Probióticos/uso terapêutico , Animais , Doenças Cardiovasculares/microbiologia , Disbiose/microbiologia , Humanos , Fenômenos Fisiológicos da Nutrição , Prebióticos/administração & dosagem
6.
Int J Mol Sci ; 22(15)2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34360574

RESUMO

Nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S), three major gasotransmitters, are involved in pleiotropic biofunctions. Research on their roles in hypertension and kidney disease has greatly expanded recently. The developing kidney can be programmed by various adverse in utero conditions by so-called renal programming, giving rise to hypertension and kidney disease in adulthood. Accordingly, early gasotransmitter-based interventions may have therapeutic potential to revoke programming processes, subsequently preventing hypertension and kidney disease of developmental origins. In this review, we describe the current knowledge of NO, CO, and H2S implicated in pregnancy, including in physiological and pathophysiological processes, highlighting their key roles in hypertension and kidney disease. We summarize current evidence of gasotransmitter-based interventions for prevention of hypertension and kidney disease in animal models. Continued study is required to assess the interplay among the gasotransmitters NO, CO, and H2S and renal programming, as well as a greater focus on further clinical translation.


Assuntos
Gasotransmissores/uso terapêutico , Hipertensão/prevenção & controle , Nefropatias/prevenção & controle , Animais , Humanos
7.
Artigo em Inglês | MEDLINE | ID: mdl-34208324

RESUMO

Introduction: Phthalates are substances that are added to plastic products to increase their plasticity. These substances are released easily into the environment and can act as endocrine disruptors. Epidemiological studies in children have showed inconsistent findings regarding the relationship between prenatal or postnatal exposure to phthalates and the risk of allergic disease. Our hypothesis is that prenatal exposure to phthalates may contribute to the development of allergies in children. Material and methods: The objective of this study was to determine the associations between urinary phthalate metabolite concentrations in pregnant women, maternal atopic diathesis, maternal lifestyle, and cord blood IgE. Pregnant mothers and paired newborns (n = 101) were enrolled from an antenatal clinic. The epidemiologic data and the clinical information were collected using standard questionnaires and medical records. The maternal blood and urine samples were collected at 24-28 weeks gestation, and cord blood IgE, IL-12p70, IL-4, and IL-10 levels were determined from the newborns at birth. The link between phthalates and maternal IgE was also assessed. To investigate the effects of phthalates on neonatal immunity, cord blood mononuclear cells (MNCs) were used for cytokine induction in another in vitro experiment. Results: We found that maternal urine monoethyl phthalate (MEP) (a metabolite of di-ethyl phthalate (DEP)) concentrations are positively correlated with the cord blood IgE of the corresponding newborns. The cord blood IL-12p70 levels of mothers with higher maternal urine MEP groups (high DEP exposure) were lower than mothers with low DEP exposure. In vitro experiments demonstrated that DEP could enhance IL-4 production of cord blood MNCs rather than adult MNCs. Conclusion: Prenatal DEP exposure is related to neonatal IgE level and alternation of cytokines relevant to Th1/Th2 polarization. This suggests the existence of a link between prenatal exposure to specific plasticizers and the future development of allergies.


Assuntos
Ácidos Ftálicos , Efeitos Tardios da Exposição Pré-Natal , Adulto , Criança , Exposição Ambiental , Feminino , Humanos , Imunoglobulina E , Recém-Nascido , Exposição Materna/efeitos adversos , Ácidos Ftálicos/toxicidade , Gravidez , Linfócitos T
8.
Molecules ; 26(13)2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34209270

RESUMO

Resveratrol butyrate esters (RBE) are derivatives of resveratrol (RSV) and butyric acid and exhibit biological activity similar to that of RSV but with higher bioavailability. The aim of this study was designed as an animal experiment to explore the effects of RBE on the serum biochemistry, and fat deposits in the offspring rats exposed to bisphenol A (BPA), along with the growth and decline of gut microbiota. We constructed an animal model of perinatal Bisphenol A (BPA) exposure to observe the effects of RBE supplementation on obesity, blood lipids, and intestinal microbiota in female offspring rats. Perinatal exposure to BPA led to weight gain, lipid accumulation, high levels of blood lipids, and deterioration of intestinal microbiota in female offspring rats. RBE supplementation reduced the weight gain and lipid accumulation caused by BPA, optimised the levels of blood lipids, significantly reduced the Firmicutes/Bacteroidetes (F/B) ratio, and increased and decreased the abundance of S24-7 and Lactobacillus, respectively. The analysis of faecal short-chain fatty acid (SCFA) levels revealed that BPA exposure increased the faecal concentration of acetate, which could be reduced via RBE supplementation. However, the faecal concentrations of propionate and butyrate were not only significantly lower than that of acetate, but also did not significantly change in response to BPA exposure or RBE supplementation. Hence, RBE can suppress BPA-induced obesity in female offspring rats, and it demonstrates excellent modulatory activity on intestinal microbiota, with potential applications in perinatological research.


Assuntos
Compostos Benzidrílicos/toxicidade , Ácido Butírico/farmacologia , Obesidade , Fenóis/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Resveratrol/farmacologia , Animais , Ácidos Graxos Voláteis/metabolismo , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Obesidade/induzido quimicamente , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/tratamento farmacológico , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Ratos , Ratos Sprague-Dawley
9.
Sci Rep ; 11(1): 11887, 2021 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-34088938

RESUMO

The aim of the study was to assess trends in the relative use of dialysis modalities in the hospital-based pediatric cohort and to determine risk factors associated with in-hospital morality among pediatric patients receiving dialysis for acute kidney injury (AKI). Patients aged < 20 years who received dialysis between 2010 and 2017 were identified from electronic health records databases of a Taiwan's healthcare delivery system. The annual uses of intermittent hemodialysis (HD), continuous and automated peritoneal dialysis (PD) and continuous kidney replacement therapy (CKRT) were assessed using Cochran-Armitage Tests for trend. Among patients who received their first dialysis as inpatients for AKI, a multivariate logistic regression model was employed to assess mortality risks associated with dialysis modalities, patient demographics, complexity of baseline chronic disease, and healthcare service use during their hospital stays. Kidney dialysis was performed 37.9 per patient per year over the study period. Intermittent hemodialysis (HD) (73.3%) was the most frequently used dialysis modality. In the inpatient setting, the relative annual use of CKRT increased over the study period, while HD use concomitantly declined (P < 0.0001). The overall in-hospital mortality rate after dialysis for AKI was 33.6%, which remained steady over time (P = 0.2411). Patients aged < 2 years [adjusted odds ratio: (aOR) 3.36; 95% confidence interval (CI) 1.34-8.93] and greater vasoactive regimen use (aOR: 17.1; 95% CI: 5.3-55.21) were significantly associated with dialysis-related mortality. Overall treatment modality used for dialysis in pediatric patients increased slowly in the study period, and HD and CRKT modality uses largely evolved in the inpatient setting. Younger ages and use of more vasoactive medication regimens were independently associated with increased early mortality in patients on AKI-dialysis.

10.
Int J Mol Sci ; 22(10)2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-34067838

RESUMO

Resveratrol can affect the physiology or biochemistry of offspring in the maternal-fetal animal model. However, it exhibits low bioavailability in humans and animals. Fifteen-week SD pregnant female rats were orally administered bisphenol A (BPA) and/or resveratrol butyrate ester (RBE), and the male offspring rats (n = 4-8 per group) were evaluated. The results show that RBE treatment (BPA + R30) compared with the BPA group can reduce the damage caused by BPA (p < 0.05). RBE enhanced the expression of selected genes and induced extramedullary hematopoiesis and mononuclear cell infiltration. RBE increased the abundance of S24-7 and Adlercreutzia in the intestines of the male offspring rats, as well as the concentrations of short-chain fatty acids (SCFAs) in the feces. RBE also increased the antioxidant capacity of the liver by inducing Nrf2, promoting the expression of HO-1, SOD, and CAT. It also increased the concentration of intestinal SCFAs, enhancing the barrier formed by intestinal cells, thereby preventing BPA-induced metabolic disruption in the male offspring rats, and reduced liver inflammation. This study identified a potential mechanism underlying the protective effects of RBE against the liver damage caused by BPA exposure during the peri-pregnancy period, and the influence of the gut microbiota on the gut-liver axis in the offspring.


Assuntos
Compostos Benzidrílicos/efeitos adversos , Hepatopatias/prevenção & controle , Fenóis/efeitos adversos , Resveratrol/farmacologia , Animais , Antioxidantes/metabolismo , Compostos Benzidrílicos/farmacologia , Butiratos/metabolismo , Ésteres/metabolismo , Ácidos Graxos Voláteis/metabolismo , Feminino , Microbioma Gastrointestinal , Fígado/metabolismo , Fígado/patologia , Hepatopatias/metabolismo , Masculino , Fenóis/farmacologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Ratos , Ratos Sprague-Dawley , Resveratrol/análogos & derivados
11.
Medicine (Baltimore) ; 100(20): e25986, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34011089

RESUMO

ABSTRACT: Thrombotic microangiopathy (TMA) syndromes are extraordinarily diverse in clinical presentations and etiologies. However, there are still a limited number of large cohort studies focusing on the underlying causes, outcomes, and response to plasmapheresis.A retrospective study was designed to understand trigger etiologies, organ dysfunctions, clinical outcomes, and efficacy of plasmapheresis in patients with TMA. The whole population of Taiwan was set up into 2 cohorts: 875 patients with TMA in the 2006 cohort (2006-2010) and 1352 patients with TMA in the 2011 cohort (2011-2015). One hundred ninety-five patients in the 2006 cohort and 272 patients in the 2011 cohort were under plasmapheresis treatment.The common underlying etiologies were pregnancy, followed by systemic lupus erythematosus, rheumatoid arthritis, transplantation and drugs, which were significantly higher than the control group. Stroke, seizure, arterial thrombosis, vascular stenosis, hypertension, myocardial infarction, and pancreatitis were the main clinical signs and extra-renal involvements. In the multivariate regression analysis, stroke, arterial thrombosis, peripheral arterial disease, and uremia were significantly higher compared with the control group. The mortality rate in TMA under plasmapheresis was significantly higher than all TMA cases (39.33% vs 15.39% in the 2006 cohort and 39.27% vs 15.06% in the 2011 cohort).This study indicated the spectrum of underlying causes, extra-renal characteristics, and the response to plasmapheresis of patients with TMA in Taiwan. Of note, the poor clinical outcomes of plasmapheresis in patients with TMA might highlight the masked underlying etiology or worse disease condition that should be noticed.


Assuntos
Plasmaferese/estatística & dados numéricos , Microangiopatias Trombóticas/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/uso terapêutico , Feminino , Glucocorticoides , Humanos , Imunossupressores/uso terapêutico , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Taiwan/epidemiologia , Microangiopatias Trombóticas/diagnóstico , Microangiopatias Trombóticas/mortalidade , Microangiopatias Trombóticas/terapia , Resultado do Tratamento , Adulto Jovem
12.
J Nutr Biochem ; 93: 108630, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33798707

RESUMO

Resveratrol, a phytochemical, has shown antioxidant properties and potential benefits in hypertension. Asymmetric dimethylarginine (ADMA)-related nitric oxide deficiency and gut microbiota-derived metabolite trimethylamine-N-oxide (TMAO) have been linked to hypertension. We aimed to test whether maternal resveratrol therapy would protect adult offspring against hypertension programmed by prenatal exposure to ADMA and TMAO. Pregnant Sprague-Dawley rats received ADMA 10 mg/kg/day (A), TMAO 0.65 mg/hr (T), ADMA+TMAO (AT), or vesicle (CV). One group of ADMA+TMAO-exposed rats received 50 mg/L of resveratrol in drinking water during pregnancy and lactation periods (ATR). Male offspring (n = 8/group) were assigned to five groups: CV, A, T, AT, and ATR. Rats were killed at 12 weeks of age. ADMA exposure caused the elevation of blood pressure in 12-week-old male offspring, which was exacerbated by TMAO exposure. Treatment with resveratrol rescued hypertension programmed by combined ADMA and TMAO exposure. This was accompanied by alterations in the compositions of gut microbiota and increased fecal butyrate levels. Both the abundance of the butyrate-producing genera Lachnospiraceae and Ruminococcaceae were augmented by resveratrol. Meanwhile, resveratrol therapy significantly increased the abundance of the Cyanobiaceae and Erysipelotrichaceae families. Moreover, the protective effects of resveratrol were related to the mediation of the renin-angiotensin system . Our data provide new insights into the protective mechanisms of resveratrol against hypertension programmed by ADMA and TMAO, including regulation of gut microbiota and their metabolites, the renin-angiotensin system, and nitric oxide pathway. Resveratrol might be a potential reprogramming strategy to protect against the hypertension of developmental origins.


Assuntos
Arginina/análogos & derivados , Hipertensão/induzido quimicamente , Hipertensão/prevenção & controle , Metilaminas/toxicidade , Resveratrol/farmacologia , Animais , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Arginina/toxicidade , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Fenômenos Fisiológicos da Nutrição Pré-Natal , Ratos , Sistema Renina-Angiotensina/efeitos dos fármacos , Resveratrol/administração & dosagem
13.
Sci Rep ; 11(1): 8202, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33859259

RESUMO

The pathophysiologies of metabolic syndrome (MS) and overactive bladder (OAB) might overlap. Using fructose-fed rats (FFRs) as a rodent model of MS we investigated the effects of tadalafil (a phosphodiesterase type 5 inhibitor) on the dysregulated insulin signalling in the bladder mucosa and bladder overactivity. Micturition behaviour was evaluated. Concentration-response curves on detrusor relaxation to insulin stimulation were examined. Expression and phosphorylation of proteins in the insulin signalling pathway were evaluated by Western blotting. Levels of detrusor cGMP and urinary nitrite and nitrate (NOx) were measured. We observed FFRs exhibited metabolic traits of MS, bladder overactivity, and impaired insulin-activated detrusor relaxation in organ bath study. A high-fructose diet also impeded insulin signalling, reflected by overexpression of IRS1/pIRS1Ser307 and pIRS2Ser731 and downregulation of PI3K/pPI3KTyr508, AKT/pAKTSer473, and eNOS/peNOSSer1177 in the bladder mucosa, alongside decreased urinary NOx and detrusor cGMP levels. Tadalafil treatment restored the reduced level of mucosal peNOS, urinary NOx, and detrusor cGMP, improved the insulin-activated detrusor relaxation, and ameliorated bladder overactivity in FFRs. These results suggest tadalafil may ameliorate MS-associated bladder overactivity by restoring insulin-activated detrusor relaxation via molecular mechanisms that are associated with preservation of IR/IRS/PI3K/AKT/eNOS pathway in the bladder mucosa and cGMP production in the bladder detrusor.

14.
Int J Mol Sci ; 22(8)2021 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-33921641

RESUMO

The increase in the incidence of cardiovascular diseases (CVDs) and kidney disease has stimulated research for strategies that could prevent, rather than just treat, both interconnected disorders. Resveratrol, a polyphenolic compound with pleiotropic biofunctions, has shown health benefits. Emerging epidemiological data supports that early life environmental insults are regarded as increased risks of developing CVDs and kidney disease in adulthood. Conversely, both disorders could be reversed or postponed by shifting interventions from adulthood to earlier stage by so-called reprogramming. The purpose of this review is first to highlight current epidemiological studies linking cardiovascular and renal programming to resulting CVD and kidney disease of developmental origins. This will be followed by a summary of how resveratrol could exert a positive influence on CVDs and kidney disease. This review also presents an overview of the evidence documenting resveratrol as a reprogramming agent to protect against CVD and kidney disease of developmental origins from animal studies and to outline the advances in understanding the underlying molecular mechanisms. Overall, this review reveals the need for future research to further clarify the reprogramming effects of resveratrol before clinical translation.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Nefropatias/prevenção & controle , Resveratrol/uso terapêutico , Animais , Doenças Cardiovasculares/metabolismo , Humanos , Nefropatias/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
15.
Int J Mol Sci ; 22(5)2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33800916

RESUMO

Gut microbiota-derived metabolites, in particular short chain fatty acids (SCFAs) and their receptors, are linked to hypertension. Fructose and antibiotics are commonly used worldwide, and they have a negative impact on the gut microbiota. Our previous study revealed that maternal high-fructose (HF) diet-induced hypertension in adult offspring is relevant to altered gut microbiome and its metabolites. We, therefore, intended to examine whether minocycline administration during pregnancy and lactation may further affect blood pressure (BP) programmed by maternal HF intake via mediating gut microbiota and SCFAs. Pregnant Sprague-Dawley rats received a normal diet or diet containing 60% fructose throughout pregnancy and lactation periods. Additionally, pregnant dams received minocycline (50 mg/kg/day) via oral gavage or a vehicle during pregnancy and lactation periods. Four groups of male offspring were studied (n = 8 per group): normal diet (ND), high-fructose diet (HF), normal diet + minocycline (NDM), and HF + minocycline (HFM). Male offspring were killed at 12 weeks of age. We observed that the HF diet and minocycline administration, both individually and together, causes the elevation of BP in adult male offspring, while there is no synergistic effect between them. Four groups displayed distinct enterotypes. Minocycline treatment leads to an increase in the F/B ratio, but decreased abundance of genera Lactobacillus, Ruminococcus, and Odoribacter. Additionally, minocycline treatment decreases plasma acetic acid and butyric acid levels. Hypertension programmed by maternal HF diet plus minocycline exposure is related to the increased expression of several SCFA receptors. Moreover, minocycline- and HF-induced hypertension, individually or together, is associated with the aberrant activation of the renin-angiotensin system (RAS). Conclusively, our results provide a new insight into the support of gut microbiota and its metabolite SCAFs in the developmental programming of hypertension and cast new light on the role of RAS in this process, which will help prevent hypertension programmed by maternal high-fructose and antibiotic exposure.


Assuntos
Antibacterianos/toxicidade , Frutose/toxicidade , Microbioma Gastrointestinal/fisiologia , Hipertensão/microbiologia , Minociclina/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Animais , Antibacterianos/administração & dosagem , Ácidos Graxos Voláteis/metabolismo , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Negativas/metabolismo , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/isolamento & purificação , Bactérias Gram-Positivas/metabolismo , Hipertensão/etiologia , Rim/efeitos dos fármacos , Rim/metabolismo , Lactação , Masculino , Minociclina/administração & dosagem , Óxido Nítrico/metabolismo , Gravidez , Ratos , Ratos Sprague-Dawley , Receptores de Superfície Celular/biossíntese , Receptores de Superfície Celular/genética , Sistema Renina-Angiotensina/fisiologia
16.
Antioxidants (Basel) ; 10(3)2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33801821

RESUMO

To expand the applications and enhance the stability and bioactivity of resveratrol (RE), and to simultaneously include the potential health benefits of short chain fatty acids (SCFA) esters of RE were prepared by Steglich reactions with acetic, propionic, and butyric acids, respectively. RE and the esterified RE-SCFA products (including RAE, RPE, and RBE) were analyzed using nuclear magnetic resonance (NMR), Fourier-transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), differential thermal analysis (DTA), and liquid chromatography-mass spectrometry (LC-MS). The FTIR and 13C NMR spectra of the esterified products included ester-characteristic peaks at 1751 cm-1 and 171 ppm, respectively. Moreover, the peaks in the range of 1700 to 1600 cm-1 in the FTIR spectra of the esterified products indicated that the esterification of RE-SCFA was successful. The TGA results revealed that the RE-SCFA esters decomposed at lower temperatures than RE. The peaks in the LC-MS profiles of the esterified products indicated the formation of mono- and diesters, and the calculated monoester synthesis rates ranged between 45.81 and 49.64%. The RE esters inhibited the Cu2+-induced low-density lipoprotein oxidation reaction, exhibited antioxidant activity in bulk oil, and effectively inhibited the hydroxyl radical-induced DNA scission. Moreover, the RE-SCFA esters had better hydrogen peroxide scavenging activity than RE. Our results are the first in the literature to successfully including short chain fatty acids in the esters of resveratrol, and the products could be used as a functional food ingredient in processed foods or can be used as dietary supplements to promote health.

17.
Int J Mol Sci ; 22(5)2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33669059

RESUMO

The renin-angiotensin-aldosterone system (RAAS) is implicated in hypertension and kidney disease. The developing kidney can be programmed by various early-life insults by so-called renal programming, resulting in hypertension and kidney disease in adulthood. This theory is known as developmental origins of health and disease (DOHaD). Conversely, early RAAS-based interventions could reverse program processes to prevent a disease from occurring by so-called reprogramming. In the current review, we mainly summarize (1) the current knowledge on the RAAS implicated in renal programming; (2) current evidence supporting the connections between the aberrant RAAS and other mechanisms behind renal programming, such as oxidative stress, nitric oxide deficiency, epigenetic regulation, and gut microbiota dysbiosis; and (3) an overview of how RAAS-based reprogramming interventions may prevent hypertension and kidney disease of developmental origins. To accelerate the transition of RAAS-based interventions for prevention of hypertension and kidney disease, an extended comprehension of the RAAS implicated in renal programming is needed, as well as a greater focus on further clinical translation.


Assuntos
Hipertensão/metabolismo , Nefropatias/metabolismo , Rim/crescimento & desenvolvimento , Néfrons/crescimento & desenvolvimento , Sistema Renina-Angiotensina , Renina/metabolismo , Adulto , Animais , Modelos Animais de Doenças , Disbiose/metabolismo , Epigênese Genética , Humanos , Hipertensão/genética , Rim/metabolismo , Nefropatias/enzimologia , Nefropatias/genética , Néfrons/citologia , Néfrons/metabolismo , Óxido Nítrico/deficiência , Óxido Nítrico/metabolismo , Estresse Oxidativo/genética , Estresse Oxidativo/fisiologia , Sistema Renina-Angiotensina/genética , Sistema Renina-Angiotensina/fisiologia
18.
Mol Nutr Food Res ; 65(11): e2001116, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33547712

RESUMO

SCOPE: Perinatal high-fat (HF) diet induces hypertension in adult offspring. Garlic, a naturally dietary source of Hydrogen sulfide (H2 S) donor, has been shown benefits in hypertension. The article examines whether maternal garlic oil supplementation can prevent hypertension induced by HF diet and elucidate its protective effects. METHODS AND RESULTS: Pregnant rats are given either a normal diet or HF diet. Rat dams are given garlic oil or vehicle daily by oral gavage at 100 mg kg-1 day-1 during pregnancy and lactation. Male offspring are sacrificed at 16 weeks of age. Garlic oil supplementation during pregnancy and lactation protected against hypertension induced by HF diet in adult male offspring. The beneficial effects of garlic oil are associated with increased renal mRNA expression and activity of H2 S-generating enzymes, increased NO bioavailability, increased plasma short chain fatty acid levels, and alterations of gut microbiota composition. Garlic oil supplementation increases abundance of genus Lactobacillus, but decreases genera Turicibacter and Staphylococcus. CONCLUSION: The data reveals associations between H2 S-generating pathway in the gut and kidneys, NO system, gut microbiota, and microbiota-derived metabolites in hypertension induced by HF intake and provide insight to garlic oil as a hypertension reprogramming strategy for further translational research.

19.
J Pediatr ; 228: 58-65.e3, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32712283

RESUMO

OBJECTIVES: To investigate the cardiovascular features and endothelium in neonates born to mothers with preeclampsia. STUDY DESIGN: In this combined observational cohort and case-control study, neonates born to mothers with normotension and mothers with preeclampsia were recruited at a neonatal intensive care unit of a tertiary medical center. Cardiovascular measurements by echocardiography and the clinical measures upon admission were analyzed. Vascular cell adhesion molecule-1 expression in umbilical arteries and in in vitro endothelial cell stimulation with plasma were examined. Continuous data were compared using nonparametric analysis, and their relationships were analyzed using linear regression. Binary logistic regression was performed in the model of adjustment of birth body weight and for multivariate analysis. RESULTS: In the cohort, almost all cardiovascular segments positively correlated to birth weight. Notably, neonates (n = 65) of mothers with preeclampsia had significantly larger coronary arteries at birth than neonates of mothers with normotension (n = 404) (median size of left main coronary artery 1.36 mm versus 1.08 mm, p <0.001; median size of right coronary artery, RCA 1.25 mm versus 1.0 mm, p <0.001). The size of the right coronary artery positively correlated to the maternal antepartum diastolic blood pressure (r = 0.298, P = .018) and was associated with in-hospital death (P < .001). Meanwhile, endothelial vascular cell adhesion molecule-1 expression was significantly increased in the umbilical arteries of the preeclamptic group and following preeclamptic cord-plasma stimulation. The latter also correlated with their relative coronary sizes. CONCLUSIONS: Neonates of mothers with preeclampsia had distinctive coronary dilatation at birth. Coronary size might be useful as a severity index of neonatal endothelial inflammation as a result of maternal preeclampsia.


Assuntos
Doença da Artéria Coronariana/etiologia , Vasos Coronários/fisiopatologia , Endotélio Vascular/fisiopatologia , Inflamação/diagnóstico , Pré-Eclâmpsia/diagnóstico , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/fisiopatologia , Dilatação Patológica/diagnóstico , Dilatação Patológica/etiologia , Dilatação Patológica/fisiopatologia , Endotélio Vascular/diagnóstico por imagem , Feminino , Seguimentos , Idade Gestacional , Humanos , Recém-Nascido , Inflamação/fisiopatologia , Masculino , Gravidez , Estudos Retrospectivos
20.
Biomedicines ; 8(12)2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33291753

RESUMO

The gut microbiota plays a critical role in kidney disease and hypertension; however, whether maternal chronic kidney disease (CKD)-induced offspring hypertension is associated with alterations of the microbiota and microbial metabolites remains elusive. Using rat as an animal model, we conducted a maternal adenine-induced CKD model to examine whether adult male offspring develop hypertension and kidney disease. As resveratrol has antioxidant and prebiotic properties, we also aimed to elucidate whether its use in pregnancy and lactation can benefit hypertension programmed by maternal CKD via mediation of the gut microbiota and oxidative stress. Female Sprague-Dawley rats received regular chow (C) or chow supplemented with 0.5% adenine (CKD) from 3 weeks before pregnancy until lactation. One group of the adenine-induced CKD pregnant rats received resveratrol (R; 50 mg/L) in drinking water during gestation and lactation. Male offspring were divided into three groups: C, CKD, and CKD+R. The microbial metabolites analyzed were short chain fatty acids (SCFAs) in feces and trimethylamine (TMA)/trimethylamine N-oxide (TMAO) in plasma. We found perinatal resveratrol therapy protected against maternal CKD-induced hypertension in adult male offspring. The overall microbial compositions and diversity of bacterial community in the three groups were different. Resveratrol therapy increased α-diversity, decreased the Firmicutes to Bacteroidetes ratio, and increased the abundance of the genera Lactobacillus and Bifidobacterium. Perinatal resveratrol therapy increased plasma TMA levels but decreased the plasma TMAO-to-TMA ratio. Although resveratrol had negligible effect on fecal concentrations of SCFAs, it increased G-protein coupled receptor-41 (GPR41) protein levels in the offspring's kidneys. Additionally, resveratrol therapy increased plasma levels of L-arginine and the L-arginine-to-ADMA ratio (AAR), and decreased oxidative stress. Overall, the protective effects of resveratrol against programmed hypertension are related to gut microbiome remodeling, including an increased abundance of beneficial microbes, mediation of the TMA-TMAO pathway, and alterations of SCFA receptors. Our results highlighted that targeting the microbiome and their metabolites might be potential therapeutic strategies to prevent maternal CKD-induced adverse pregnancy and offspring outcomes.

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