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1.
Cell Death Dis ; 14(7): 446, 2023 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-37468478

RESUMO

MicroRNA-150 (miR-150) is conserved between rodents and humans, is significantly downregulated during heart failure (HF), and correlates with patient outcomes. We previously reported that miR-150 is protective during myocardial infarction (MI) in part by decreasing cardiomyocyte (CM) apoptosis and that proapoptotic small proline-rich protein 1a (Sprr1a) is a direct CM target of miR-150. We also showed that Sprr1a knockdown in mice improves cardiac dysfunction and fibrosis post-MI and that Sprr1a is upregulated in pathological mouse cardiac fibroblasts (CFs) from ischemic myocardium. However, the direct functional relationship between miR-150 and SPRR1A during both post-MI remodeling in mice and human CF (HCF) activation was not established. Here, using a novel miR-150 knockout;Sprr1a-hypomorphic (Sprr1ahypo/hypo) mouse model, we demonstrate that Sprr1a knockdown blunts adverse post-MI effects caused by miR-150 loss. Moreover, HCF studies reveal that SPRR1A is upregulated in hypoxia/reoxygenation-treated HCFs and is downregulated in HCFs exposed to the cardioprotective ß-blocker carvedilol, which is inversely associated with miR-150 expression. Significantly, we show that the protective roles of miR-150 in HCFs are directly mediated by functional repression of profibrotic SPRR1A. These findings delineate a pivotal functional interaction between miR-150 and SPRR1A as a novel regulatory mechanism pertinent to CF activation and ischemic HF.


Assuntos
MicroRNAs , Infarto do Miocárdio , Animais , Humanos , Camundongos , Modelos Animais de Doenças , Fibroblastos/metabolismo , Fibrose , MicroRNAs/genética , MicroRNAs/metabolismo , Infarto do Miocárdio/metabolismo , Miocárdio/patologia , Miócitos Cardíacos/metabolismo , Remodelação Ventricular/genética
2.
J Cardiovasc Dev Dis ; 10(4)2023 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-37103045

RESUMO

Noncoding RNAs (ncRNAs) play fundamental roles in cardiac development and cardiovascular diseases (CVDs), which are a major cause of morbidity and mortality. With advances in RNA sequencing technology, the focus of recent research has transitioned from studies of specific candidates to whole transcriptome analyses. Thanks to these types of studies, new ncRNAs have been identified for their implication in cardiac development and CVDs. In this review, we briefly describe the classification of ncRNAs into microRNAs, long ncRNAs, and circular RNAs. We then discuss their critical roles in cardiac development and CVDs by citing the most up-to-date research articles. More specifically, we summarize the roles of ncRNAs in the formation of the heart tube and cardiac morphogenesis, cardiac mesoderm specification, and embryonic cardiomyocytes and cardiac progenitor cells. We also highlight ncRNAs that have recently emerged as key regulators in CVDs by focusing on six of them. We believe that this review concisely addresses perhaps not all but certainly the major aspects of current progress in ncRNA research in cardiac development and CVDs. Thus, this review would be beneficial for readers to obtain a recent picture of key ncRNAs and their mechanisms of action in cardiac development and CVDs.

3.
Cell Death Discov ; 8(1): 504, 2022 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-36585403

RESUMO

The ß1-adrenergic receptor (ß1AR) is found primarily in hearts (mainly in cardiomyocytes [CMs]) and ß-arrestin-mediated ß1AR signaling elicits cardioprotection through CM survival. We showed that microRNA-150 (miR-150) is upregulated by ß-arrestin-mediated ß1AR signaling and that CM miR-150 inhibits maladaptive remodeling post-myocardial infarction. Here, we investigate whether miR-150 rescues cardiac dysfunction in mice bearing CM-specific abrogation of ß-arrestin-mediated ß1AR signaling. Using CM-specific transgenic (TG) mice expressing a mutant ß1AR (G protein-coupled receptor kinase [GRK]-ß1AR that exhibits impairment in ß-arrestin-mediated ß1AR signaling), we first generate a novel double TG mouse line overexpressing miR-150. We demonstrate that miR-150 is sufficient to improve cardiac dysfunction in CM-specific GRK-ß1AR TG mice following chronic catecholamine stimulation. Our genome-wide circular RNA, long noncoding RNA (lncRNA), and mRNA profiling analyses unveil a subset of cardiac ncRNAs and genes as heretofore unrecognized mechanisms for beneficial actions of ß1AR/ß-arrestin signaling or miR-150. We further show that lncRNA Gm41664 and GDAP1L1 are direct novel upstream and downstream regulators of miR-150. Lastly, CM protective actions of miR-150 are attributed to repressing pro-apoptotic GDAP1L1 and are mitigated by pro-apoptotic Gm41664. Our findings support the idea that miR-150 contributes significantly to ß1AR/ß-arrestin-mediated cardioprotection by regulating unique ncRNA and gene signatures in CMs.

4.
Circ Heart Fail ; 15(4): e008686, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35000421

RESUMO

BACKGROUND: MicroRNA-150 (miR-150) plays a protective role in heart failure (HF). Long noncoding RNA, myocardial infarction-associated transcript (MIAT) regulates miR-150 function in vitro by direct interaction. Concurrent with miR-150 downregulation, MIAT is upregulated in failing hearts, and gain-of-function single-nucleotide polymorphisms in MIAT are associated with increased risk of myocardial infarction (MI) in humans. Despite the correlative relationship between MIAT and miR-150 in HF, their in vivo functional relationship has never been established, and molecular mechanisms by which these 2 noncoding RNAs regulate cardiac protection remain elusive. METHODS: We use MIAT KO (knockout), Hoxa4 (homeobox a4) KO, MIAT TG (transgenic), and miR-150 TG mice. We also develop DTG (double TG) mice overexpressing MIAT and miR-150. We then use a mouse model of MI followed by cardiac functional, structural, and mechanistic studies by echocardiography, immunohistochemistry, transcriptome profiling, Western blotting, and quantitative real-time reverse transcription-polymerase chain reaction. Moreover, we perform expression analyses in hearts from patients with HF. Lastly, we investigate cardiac fibroblast activation using primary adult human cardiac fibroblasts and in vitro assays to define the conserved MIAT/miR-150/HOXA4 axis. RESULTS: Using novel mouse models, we demonstrate that genetic overexpression of MIAT worsens cardiac remodeling, while genetic deletion of MIAT protects hearts against MI. Importantly, miR-150 overexpression attenuates the detrimental post-MI effects caused by MIAT. Genome-wide transcriptomic analysis of MIAT null mouse hearts identifies Hoxa4 as a novel downstream target of the MIAT/miR-150 axis. Hoxa4 is upregulated in cardiac fibroblasts isolated from ischemic myocardium and subjected to hypoxia/reoxygenation. HOXA4 is also upregulated in patients with HF. Moreover, Hoxa4 deficiency in mice protects the heart from MI. Lastly, protective actions of cardiac fibroblast miR-150 are partially attributed to the direct and functional repression of profibrotic Hoxa4. CONCLUSIONS: Our findings delineate a pivotal functional interaction among MIAT, miR-150, and Hoxa4 as a novel regulatory mechanism pertinent to ischemic HF.


Assuntos
Insuficiência Cardíaca , Proteínas de Homeodomínio , MicroRNAs , Infarto do Miocárdio , RNA Longo não Codificante , Fatores de Transcrição , Animais , Modelos Animais de Doenças , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/metabolismo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Infarto do Miocárdio/genética , Infarto do Miocárdio/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Remodelação Ventricular
5.
Methods Cell Biol ; 166: 309-348, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34752338

RESUMO

Cardiovascular diseases (CVDs) represent the foremost cause of mortality in the United States and worldwide. It is estimated that CVDs account for approximately 17.8 million deaths each year. Despite the advances made in understanding cellular mechanisms and gene mutations governing the pathophysiology of CVDs, they remain a significant cause of mortality and morbidity. A major segment of mammalian genomes encodes for genes that are not further translated into proteins. The roles of the majority of such noncoding ribonucleic acids (RNAs) have been puzzling for a long time. However, it is becoming increasingly clear that noncoding RNAs (ncRNAs) are dynamically expressed in different cell types and have a comprehensive selection of regulatory roles at almost every step involved in DNAs, RNAs and proteins. Indeed, ncRNAs regulate gene expression through epigenetic interactions, through direct binding to target sequences, or by acting as competing endogenous RNAs. The profusion of ncRNAs in the cardiovascular system suggests that they may modulate complex regulatory networks that govern cardiac physiology and pathology. In this review, we summarize various functions of ncRNAs and highlight the recent literature on interactions between ncRNAs with an emphasis on cardiovascular disease regulation. Furthermore, as the broad-spectrum of ncRNAs potentially establishes new avenues for therapeutic development targeting CVDs, we discuss the innovative prospects of ncRNAs as therapeutic targets for CVDs.


Assuntos
Doenças Cardiovasculares , MicroRNAs , Animais , Doenças Cardiovasculares/genética , Epigênese Genética/genética , Mamíferos/genética , MicroRNAs/genética , RNA , RNA não Traduzido/genética
6.
JCI Insight ; 6(18)2021 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-34403363

RESUMO

MicroRNA-150 (miR-150) is downregulated in patients with multiple cardiovascular diseases and in diverse mouse models of heart failure (HF). miR-150 is significantly associated with HF severity and outcome in humans. We previously reported that miR-150 is activated by ß-blocker carvedilol (Carv) and plays a protective role in the heart using a systemic miR-150 KO mouse model. However, mechanisms that regulate cell-specific miR-150 expression and function in HF are unknown. Here, we demonstrate that potentially novel conditional cardiomyocyte-specific (CM-specific) miR-150 KO (miR-150 cKO) in mice worsens maladaptive cardiac remodeling after myocardial infarction (MI). Genome-wide transcriptomic analysis in miR-150 cKO mouse hearts identifies small proline-rich protein 1a (Sprr1a) as a potentially novel target of miR-150. Our studies further reveal that Sprr1a expression is upregulated in CMs isolated from ischemic myocardium and subjected to simulated ischemia/reperfusion, while its expression is downregulated in hearts and CMs by Carv. We also show that left ventricular SPRR1A is upregulated in patients with HF and that Sprr1a knockdown in mice prevents maladaptive post-MI remodeling. Lastly, protective roles of CM miR-150 are, in part, attributed to the direct and functional repression of proapoptotic Sprr1a. Our findings suggest a crucial role for the miR-150/SPRR1A axis in regulating CM function post-MI.


Assuntos
Proteínas Ricas em Prolina do Estrato Córneo/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Infarto do Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Remodelação Ventricular/genética , Antagonistas Adrenérgicos beta/farmacologia , Animais , Apoptose/fisiologia , Carvedilol/farmacologia , Proteínas Ricas em Prolina do Estrato Córneo/metabolismo , Regulação para Baixo , Feminino , Expressão Gênica/efeitos dos fármacos , Perfilação da Expressão Gênica , Insuficiência Cardíaca/metabolismo , Ventrículos do Coração/metabolismo , Humanos , Masculino , Camundongos , Camundongos Knockout , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/metabolismo , Regulação para Cima
7.
Artigo em Inglês | MEDLINE | ID: mdl-33688366

RESUMO

MATERIALS AND METHODS: Bark extracts of these plants (1 and 25 µg/mL) were added 3 hours before coincubating H9c2 cardiomyoblasts with Dox (0.5 and 1 µM) for 24 hours more. We measured cell mass and metabolic viability, mitochondrial transmembrane potential, superoxide anion content, and activity-like of caspase-3 and caspase-9 following treatment with the extracts and/or Dox. Also, selenium and vitamin C contents were measured in the plant extracts. RESULTS: The results confirmed that Dox treatment decreased cell mass, mitochondrial membrane potential and metabolic viability, increased mitochondrial superoxide anion, and stimulated caspase-3 and caspase-9-like activities. Pretreatment of the cells with the plant extracts significantly inhibited Dox cytotoxicity, with more significant results at the higher concentration. Measurements of selenium and vitamin C in the extracts revealed higher concentration of both when compared with other Cameroonian spices. CONCLUSION: Both extracts of A. lepidophyllus and M. myristica were effective against Dox-induced cytotoxicity, most likely due to their content in antioxidants.

8.
ScientificWorldJournal ; 2019: 5236851, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30940993

RESUMO

BACKGROUND: Liver diseases are a global health problem. Medicinal plants are being increasingly used to manage a wide variety of diseases including liver disorders. The aim of this study was to investigate the antioxidant properties and hepatoprotective activity of polyphenolic extract from the fruits of Tetrapleura tetraptera (T. tetraptera). RESULTS: The extract of T. tetraptera was administered at doses of 50 mg/kg and 100 mg/kg for 07 per os to rats before the induction of hepatotoxicity with of 2 ml/kg of 1:1 (v/v) carbon tetrachloride (CCl4) and olive oil through intraperitoneal route. The in vitro antioxidant and radical scavenging properties of T. tetraptera were conducted by the FRAP method, the phosphomolybdate method, and the inhibition potential of DPPH, ABTS, OH, and NO radicals. The extraction yield of T. tetraptera was 19.35%. This extract contains polyphenols (273.48 mg CAE/g DM), flavonoids (5.2549 mg SE/g DM), and flavonols (1.615 mg SE/g DM). This extract showed in vitro antioxidant activity, an inhibitor power of various free radicals, and radical scavenging potential dose-dependent. The fifty-percent inhibitory concentration of the extract (IC50) for the studied radical varied from 28.16 to 136 µg/L. In rats treated with the extract of T. tetraptera, in a dose-dependent manner, the levels of hepatotoxicity markers such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) significantly increased while the enzyme activities of superoxide dismutase (SOD), catalase (CAT), and the level of reduced glutathione (GHS) significantly increased compared to the control group. CONCLUSIONS: The extracts from the fruit of T. tetraptera demonstrate antioxidant activity and hepatoprotective effects.


Assuntos
Antioxidantes/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Extratos Vegetais/uso terapêutico , Substâncias Protetoras/uso terapêutico , Tetrapleura/química , Alanina Transaminase/metabolismo , Fosfatase Alcalina/metabolismo , Antioxidantes/isolamento & purificação , Aspartato Aminotransferases/metabolismo , Camarões , Tetracloreto de Carbono , Catalase/metabolismo , Glutationa/metabolismo , Fenóis , Extratos Vegetais/isolamento & purificação , Plantas Medicinais/química , Substâncias Protetoras/isolamento & purificação , Superóxido Dismutase/metabolismo
9.
Artigo em Inglês | MEDLINE | ID: mdl-28852413

RESUMO

Ferric nitrilotriacetate (Fe-NTA) is a highly reactive compound used to induce degenerative disorders through oxidative stress (OS). Zanthoxylum heitzii (Z. heitzii) is a spice used as a medicinal plant to treat a variety of illnesses. This study investigated the ability of extracts from the leaves, fruits, roots, and barks of Z. Heitzii to inhibit Fe-NTA mediated oxidative damage in rats. The supernatant of rat liver homogenates was pretreated with the extracts for one hour before the induction of oxidative damage using a solution of Fe-NTA (400 mM). The activities of superoxide dismutase (SOD), catalase, and peroxidases were measured together with the marker of lipid peroxidation and the level of glutathione. The pretreated groups showed a significant increase in the activity of SOD, catalase, and peroxidases. The methanolic extract from the leaves of Z. heitzii (36.78 ± 3.30) and aqueous extract from the fruits (37.01 ± 2.52) showed the highest activities of SOD in the liver. The lowest concentration of MDA was found in the liver, and the glutathione was greater in the brain. Conclusively, these results suggest that Z. heitzii might be a chemoprotector which may be used in for prevention of distinct types of diseases induced by oxidative stress.

10.
BMC Res Notes ; 10(1): 186, 2017 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-28577561

RESUMO

BACKGROUND: Elevated titers of antibodies against oxidized low-density lipoproteins-cholesterol (ox-LDL-Ab) have been reported among professional athletes, paradoxically reflecting an increased risk of developing atherogenic and/or cardiovascular events. This study aimed to determine titers of ox-LDL-Ab in a group of Cameroonian professional soccer players, and evaluate their evolution during part of a competition season as well as the plasmatic antioxidant status to find out if this latter correlates with ox-LDL-Ab . METHODS: We conducted a descriptive cohort study in 2012 including 18 healthy male soccer players. Three samplings were performed in March (T1), May (T2), and July 2012 (T3) to assess the lipid profile, titers of ox-LDL-Ab, and plasmatic concentrations of four antioxidants: the ferric reducing antioxidant power (FRAP), reduced glutathione (GSH), superoxide dismutase (SOD), and uric acid. RESULTS: Ages ranged from 16 to 28 years with a median (interquartile range) of 19.5 (19-23) years. Total cholesterol, high-density lipoproteins-cholesterol (HDL-C), low-density lipoproteins-cholesterol (LDL-C) and triglycerides varied within normal ranges throughout the three samplings. While total cholesterol and LDL-C titers increased significantly (p = 0.003 and p = 0.006, respectively), triglycerides and HDL-C values varied non-significantly throughout the measurements (p = 0.061 and p = 0.192, respectively). The median ox-LDL-Ab titers were respectively: 653.3 (468.2-838.8) mIU/ml at T1, 777.7 (553.7-1150.7) mIU/ml at T2, and 1037.7 (901.7-1481.5) mIU/ml at T3. Overall, ox-LDL-Ab titers increased significantly from T1 to T3 (p = 0.006). Concomitantly, uric acid and FRAP concentrations decreased significantly (p = 0.001 and p = 0.003, respectively); on the contrary, GSH and SOD values increased, but insignificantly (p = 0.115 and p = 0.110, respectively). There was a positive and significant correlation between ox-LDL-Ab and HDL-C (ρ = 0.519, p = 0.027), and between ox-LDL-Ab and SOD (ρ = 0.504, p = 0.033) at T2. Ox-LDL-Ab values were expected to increase with each new visit (ß = 201.1; p = 0.041) and each IU/ml of SOD titers (ß = 23.6; p = 0.019). CONCLUSION: These Cameroonian professional soccer players exhibited high levels of ox-LDL-Ab reflecting elevated levels of oxidatively-modified LDL-C particles with an increment over time, this being insufficiently counterbalanced by the antioxidant defense mechanisms. As a consequence, they may be at increased atherogenic and cardiovascular risks.


Assuntos
Aterosclerose/sangue , Aterosclerose/imunologia , Atletas , Futebol , Adolescente , Adulto , Antioxidantes/metabolismo , Autoanticorpos/sangue , Autoanticorpos/imunologia , Camarões , LDL-Colesterol/sangue , Estudos de Coortes , Glutationa/sangue , Humanos , Lipídeos/sangue , Lipoproteínas LDL/imunologia , Masculino , Análise de Regressão , Fatores de Risco , Estações do Ano , Superóxido Dismutase/sangue , Ácido Úrico/sangue , Adulto Jovem
11.
Int Sch Res Notices ; 2017: 9501675, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28529969

RESUMO

Introduction. Several plant preparations like a mixture of aqueous extracts of Spilanthes africana; Portulaca oleracea; and Sida rhombifolia are currently utilized in Foumban (West Cameroon) to manage diabetes. The aim of this study is to investigate the antidiabetic property of the aqueous mixture of three plant extracts (1 : 1 : 1) on streptozotocin induced diabetes rats. Methods. Diabetes was induced to rats by intraperitoneal (i.p.) injection of streptozotocin (STZ) at a dose of 50 mg/kg b.w. The diabetic rats received different dosages of the mixture of extracts for 21 days and glibenclamide 6.5 mg/kg b.w. as positive control. Results. The results showed that the mixture of extracts significantly (p < 0.05) decreased the level of the glycaemia, the total cholesterol, triglyceride, and LDL-cholesterol as well as MDA, AST, ALT, and creatinine levels. It also increased significantly the concentration of HDL-cholesterol, glutathione, and TAOS. A great reduction of the atherogenic indexes CT/HDL and LDL/HDL of the treated groups was observed. Each extract and the mixture demonstrated significant scavenging property on DPPH and OH radicals and present a good antioxidant property. Conclusion. The mixture of plant extracts has hypoglycemic, antioxidant, and hypolipidemic properties and can be used for the management of diabetes mellitus.

12.
BMC Res Notes ; 10(1): 141, 2017 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-28356165

RESUMO

BACKGROUND AND PURPOSE: Studies demonstrate that free radicals are involved in the pathogenesis of diabetic complications. The aim of this study was to determine the implication of total antioxidant capacity (TAC) and some enzymatic and non-enzymatic antioxidants as suitable biomarkers of diabetic complications risk factors. METHODS: A total of 90 patients (70 patients with or without diabetic complications +20 normal healthy) were examined by evaluating the level of lipid peroxidation, nitrogen monoxide (NO), fasting blood glucose, glycated haemoglobin (HbA1c), enzymatic and non-enzymatic antioxidants using standard spectrophotometric methods. RESULTS: The fasting blood glucose and HbA1c levels were respectively 2.05 and 2.32 times higher in the group of patients with diabetes and complications (DPWC) compared to those of healthy persons. A statistically higher level of malondialdehyde (MDA), NO and TAC was observed in a group of patients with diabetes and complications compared to those without complications (DPNC). A significant positive correlation was found between catalase (CAT) and fasting blood glucose while a significant and negative correlation was noted between reduced glutathione (GSH) and fasting blood glucose. Also was noted a significant relationship between HbA1c and other markers of oxidative stress. CONCLUSIONS: The results suggest that the plasma levels of CAT, TAC and reduced glutathione could give information on the risk of developing complications of diabetes, considering that the modification of these biomarkers levels were associated with oxidative stress.


Assuntos
Antioxidantes/metabolismo , Biomarcadores/sangue , Diabetes Mellitus Tipo 2/sangue , Hiperglicemia/sangue , Adulto , Idoso , Glicemia/metabolismo , Camarões , Catalase/sangue , Diabetes Mellitus Tipo 2/complicações , Jejum/sangue , Feminino , Glutationa/sangue , Hemoglobinas Glicadas/metabolismo , Humanos , Hiperglicemia/complicações , Peroxidação de Lipídeos , Masculino , Malondialdeído/sangue , Pessoa de Meia-Idade , Óxido Nítrico/sangue , Estresse Oxidativo , Superóxido Dismutase/sangue
13.
J Complement Integr Med ; 14(1)2017 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-28214348

RESUMO

Background The present study focused on the antioxidant, phenolic profile and free radical scavenging-mediated protective effect of leaves extracts of Syzygium guineense var. macrocarpum against ferric nitriloacetate-induced stress in the liver, heart, kidney and brain tissues of Wistar rats homogenates. Methods Spectrophotometric standardized methods were used to determine the free radical scavenging potential, antioxidant and protective properties of plant extracts on rat homogenates. Results All the extracts showed a concentration-dependent free radical quenching potential, and the ability to protect all the tested organs by inhibiting the lipid peroxidation and potentiating or restoring the activity of enzymatic and non enzymatic markers. The polyphenolic profile revealed the presence of at least one simple phenolic acid (gallic, caffeic, para-coumaric acid) although the majority (6 out of 14) of the compounds used as standard are present in the aqueous and aqueous-ethanol extracts. Conclusions Ethanolic extract of leaves of S. guineense var macrocarpum (SGETOH) exhibited the highest phenol content and appeared as the best extract taking into consideration the antioxidant and organo-protective activities tested.


Assuntos
Antioxidantes/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fenóis/farmacologia , Extratos Vegetais/farmacologia , Syzygium/química , Animais , Encéfalo/efeitos dos fármacos , Compostos Férricos , Coração/efeitos dos fármacos , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Ácido Nitrilotriacético/análogos & derivados , Fenóis/análise , Extratos Vegetais/química , Folhas de Planta/química , Polifenóis/análise , Polifenóis/farmacologia , Substâncias Protetoras/análise , Substâncias Protetoras/farmacologia , Ratos Wistar
14.
BMC Nutr ; 3: 25, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-32153807

RESUMO

BACKGROUND: Spirulina platensis produced in Nomayos (Cameroon) is used as a dietary supplement. S. platensis is known as a neutraceutical with many beneficial effects on humans like lipid-lowering action. This study aims to investigate the mechanism of hypolipidemic action of aqueous extract of Spirulina platensis (S. platensis) through the toxicological studies. METHODS: In this study, we included two month old Wistar rats, weighing between 180 and 200 g. Aqueous S. platensis was extracted and prepared using standard methods. The rats received a supplementation of S. platensis at 5000 mg/Kg of body weight as single dose in acute toxicity whereas different doses (250, 500, 1000 mg / kg body weight) were administered in subacute toxicity compared to control. Acute and subacute toxicities were determined according to the guidelines 420 (14 days) and 407 (28 days) of the Organization for Economic Cooperation and Development (OECD) respectively. Biochemical parameters such as urea, creatinine, total and direct bilirubin, lipid profile and transaminases; and histopathological analysis of the liver and kidneys were used to evaluate the toxicity of S. platensis on these Wistar rats. Plasmatic hydroxymethyl glutaryl coenzyme A reductase (HMG CoA reductase) and lecithine cholesterol acyl transferase (LCAT) were performed to explain the lipid-lowering action of S. platensis. Histopathological analysis of the liver and kidneys was performed. RESULTS: Our results show a decrease in total cholesterol for male rats (from 84 to 74 mg/dl) when the dose of S. platensis increased; this reduction of the total cholesterol level in male rats was significant at 500 mg/kg. There was also a significant inhibition of HMG CoA reductase in a dose dependent manner between 25 and 84.5 fold compared to the control in both male and female groups. At the dose of 250 mg/kg bw, the level of LCAT was higher compared with other groups and control, but the difference was not statistically significant. A slight inflammation in the liver and the mesangial hyperplasia of the renal glomeruli was revealed by the histopathological investigation in subacute toxicity. CONCLUSION: Spirulina platensis from Cameroon appears to have little toxic effects and may demonstrate hypolipidemic activity through the activation of LCAT.

15.
BMC Clin Pathol ; 16: 15, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27688734

RESUMO

BACKGROUND: Sickle cell disease (SCD) is a class of hemoglobinopathy resulting from a single mutation in the ß-globin chain inducing the substitution of valine for glutamic acid at the sixth amino acid position which leads to the production of abnormal haemoglobin (haemoglobin S [HbS]). Studies demonstrated the implication of oxidative stress in the development of the sickle cell disease. METHODS: The study aim was to determine the level of oxidative stress markers in a group of sickle cell homozygous patients (SS) in the Yaounde Central Hospital above 15 years of age. Hemolysates obtained from patients were used to investigate some oxidative stress markers including malondialdehyde (MDA), nitric oxide (NO), catalase (CAT), superoxide dismutase (SOD), peroxidase, total antioxidant capacity (TAC) and total protein concentration. RESULTS: Eighty four individuals, 42 males and 42 females participated (50 % each) with an age range of 15 to 55 years. The levels of markers were significantly higher in the healthy AA group than sickle (SS) (p < 0.05), with the exception of MDA which was significantly high in sickle cell (SS) patients than healthy (p = 0.037). With respect to the gender, both healthy and SS females showed a greater Total anti-oxidant capacity (65 µM) compared to the males (55 µM). CONCLUSION: The increase in the oxidative stress level especially MDA in sickle cell homozygous patients compared to healthy AA individuals confirms that oxidative stress is involved in the pathogenesis of the sickle cell disease.

16.
BMC Complement Altern Med ; 16(1): 315, 2016 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-27561333

RESUMO

BACKGROUND: Overconsumption of oxygen in mammalian cells often lead to the production of reactive oxygen species (ROS) resulting from different mechanisms. Escape of scavenging enzymes/components or nutritional failure are the most important origins. Plant-derived molecules may protect biological molecules either by quenching free radicals, delaying or preventing the ROS formation or by restoring antioxidant enzymes activities. The present study assessed the antioxidant, phenolic profile and protective effect of barks extracts of Syzyguim guineense var macrocarpum against ferric nitriloacetate-induced stress in the liver, heart kidney and brain tissues of wistar rat homogenates. METHODS: Three extracts (aqueous, ethanol and aqueous-ethanol) from the barks of S. guineense var macrocarpum were used in this study. The spectrophotometric standardized methods were used to determine the free radical scavenging and antioxidant potential of the extracts. The protective properties of these plant extracts were also investigated as well as the quantification of secondary metabolites content (total phenolic, flavonoids and flavonols content). The HPLC method helped for characterizing phenolic compounds present in these extracts. RESULTS AND DISCUSSION: All the extracts exhibited a free radical scavenging potential in a concentration dependent manner which varied from 15.18 ± 0.80 to 97.15 ± 0.71 % depending to the type of extract and the method used. The ethanol extract had the higher phenolic content (432.85 mg QE/g extract), including total flavonoids (961.66 mg QE/g extract) and flavonols content (25.12 mg QE/g extract) and higher total antioxidant capacity. Among the phenolic compounds present in the extracts, the HLPC profile revealed the presence of syringic acid and apigenin in all the extracts. The extracts demonstrated their protective effect mostly in liver and brain homogenates by delaying or preventing lipid peroxidation, restoring enzymatic activities and enhancing glutathione levels. CONCLUSION: The overall results demonstrated that the extracts exhibited significant antioxidant and protective effects in liver and brain liver homogenates.


Assuntos
Compostos Férricos/toxicidade , Ácido Nitrilotriacético/análogos & derivados , Estresse Oxidativo/efeitos dos fármacos , Casca de Planta/química , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Syzygium/química , Animais , Glutationa/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Ácido Nitrilotriacético/toxicidade , Extratos Vegetais/química , Substâncias Protetoras/química , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo
17.
Artigo em Inglês | MEDLINE | ID: mdl-26356679

RESUMO

The aim of the present study was to investigate the antioxidant activity and protective potential of T. tetraptera extracts against ion toxicity. The antioxidant activity of the extracts was investigated spectrophotometrically against several radicals (1,1-diphenyl-2-picrylhydrazyl (DPPH(•)), 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS(•)), hydroxyl radical (HO(•)), and nitric oxide (NO(•))), followed by the ferric reducing power, total phenols, flavonoid, and flavonol contents. The effects of the extracts on catalase (CAT), superoxide dismutase (SOD), and peroxidase activities were also determined using the standard methods as well as the polyphenol profile using HPLC. The results showed that the hydroethanolic extract of T. tetraptera (CFH) has the lowest IC50 value with the DPPH, ABTS, OH, and NO radicals. The same extract also exhibited the significantly higher level of total phenols (37.24 ± 2.00 CAE/g dried extract); flavonoids (11.36 ± 1.88 QE/g dried extract); and flavonols contents (3.95 ± 0.39 QE/g dried extract). The HPLC profile of T. tetraptera revealed that eugenol (958.81 ± 00 mg/g DW), quercetin (353.78 ± 00 mg/g DW), and rutin (210.54 ± 00 mg/g DW) were higher in the fruit than the bark extracts. In conclusion, extracts from T. tetraptera may act as a protector against oxidative mediated ion toxicity.

18.
BMC Res Notes ; 8: 344, 2015 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-26264271

RESUMO

BACKGROUND: Several studies described the phytochemical constituents of plants in relation with the free radical scavenging property and inhibition of lipid peroxidation. This study investigated the in vitro antioxidant property, and the protective effects of ethanolic and aqueous ethanol extract of the leaves and barks of Afrostyrax lepidophyllus (Huaceae) against ion mediated oxidative damages. METHODS: Four extracts (ethanol and aqueous-ethanol) from the leaves and barks of A. lepidophyllus were used in this study. The total phenols content, the antiradical and antioxidant properties were determined using standard colorimetric methods. RESULTS: The plant extracts had a significant scavenging potential on the 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl (OH), nitrite oxide (NO) and 2,2-azinobis (3-ethylbenzthiazoline)-6-sulfonic acid (ABTS) radicals with the IC50 varied between 47 and 200 µg/mL depending on the part of plant and the type of extract. The ethanol extract of A. lepidophyllus bark (GEE) showed the highest polyphenolic (35.33 ± 0.29) and flavonoid (12.00 ± 0.14) content. All the tested extracts demonstrated a high protective potential with the increased of superoxide dismutase, catalase and peroxidase activities. CONCLUSION: Afrostyrax lepidophyllus extracts exhibited higher antioxidant potential and significant protective potential on liver enzymes.


Assuntos
Sequestradores de Radicais Livres , Fígado/enzimologia , Oxigênio/química , Casca de Planta/enzimologia , Extratos Vegetais/química , Árvores , Animais , Antioxidantes/química , Benzotiazóis/química , Compostos de Bifenilo , Catalase/biossíntese , Catalase/metabolismo , Colorimetria , Etanol/química , Flavonoides/química , Radicais Livres , Radical Hidroxila/química , Concentração Inibidora 50 , Íons , Peroxidação de Lipídeos , Molibdênio/química , Óxido Nítrico/química , Peroxidase/biossíntese , Fenol/química , Picratos , Análise de Componente Principal , Ratos , Ratos Wistar , Ácidos Sulfônicos/química , Superóxido Dismutase/biossíntese
19.
Nutr J ; 14: 70, 2015 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-26195001

RESUMO

BACKGROUND: Micronutrient deficiencies occur early in Human Immunodeficiency Virus (HIV) infections they have reverse effects on the nutritional status. The diet supplementation with a natural nutraceutical rich in proteins and micronutrient like Spirulina platensis, may be effective and efficient in delaying HIV disease progression by frequently reported improvement in immune response. METHODS: A prospective single-blind, randomized, multicenter study conducted on 320 HIV-1 ARV-naïve participants for 12 months. Participants received either S. platensis supplementation and standard care or standard care and local balanced diet without S. platenis. Selected hematological and biochemical as well as CD4 count cells, viral load copies were assessed at three separate times. RESULTS: Among the 169 ART-naïve participants enrolled in the study, the female was mostly represented (67.1%). The significant increase of CD4 count cells (596.32-614.92 cells count) and significant decrease of viral load levels (74.7 × 10(3)-30.87 × 10(3) copies/mL) of the patients who received a supplementation of S. platensis was found after 6 months of treatment. Haemoglobin level was also significantly higher in the same group while the fasting blood glucose concentration decreased after 12 months compared to control. CONCLUSION: A daily supplementation with S. platensis to diet combined with a reasonable balanced diet has significantly increased the CD4 cells and reduced the viral load after 6 months. Further studies are recommended among a large specific group of people infected by the HIV in order to investigate the mechanisms involved on the effect of S. platensis on immune system.


Assuntos
Suplementos Nutricionais , Infecções por HIV/terapia , Spirulina/metabolismo , Adulto , Índice de Massa Corporal , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/metabolismo , Camarões , Dieta , Feminino , Seguimentos , Infecções por HIV/sangue , Humanos , Estudos Longitudinais , Masculino , Micronutrientes/administração & dosagem , Micronutrientes/sangue , Micronutrientes/deficiência , Estado Nutricional , Estudos Prospectivos , Método Simples-Cego , Carga Viral
20.
J Complement Integr Med ; 12(3): 195-204, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25941917

RESUMO

Reactive oxygen species (ROS), products of normal cell metabolism may cause damage to biological macromolecules leading to severe health threats when they are present in high concentrations. Aromatic plants contain phytochemicals rich of antioxidants that prevent oxidant formation or scavenge oxidants produced under oxidative stress conditions. In the present study, we investigated the free radical scavenging effects, the antioxidant and ion toxicity preventive effect of Xylopia aethiopica (X. aethiopica), a plant of the family of Annonaceae used as spice in Cameroon. The scavenging properties of extracts of X. aethiopica were tested on 2, 2-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO), hydroxyl (OH), 2,2'-azinobis(3-ethylbenzthiazoline)-6-sulfonic acid (ABTS) radicals. The total antioxidant capacity was assayed by ferric reducing ability of plasma (FRAP), phosphomolybdenum antioxidant power (PAP), reduction assays. The protective potential was carried on superoxide dismutase (SOD), catalase and peroxidases. The results showed that both the ethanolic (BEE) and the hydroethanolic (BEH) extracts from the barks of X. aethiopica scavenged all the tested radicals. The sample BEH showed the highest total antioxidant capacity both in the FRAP and the PAP. This result was positively correlated to its higher phenolic content (30.74±0.44 CAE/g dried extract). The higher protective capacity of BEH on SOD, catalase and peroxidase activities was comparable to that of the vitamin C used as standard. In conclusion, X. aethiopica has a higher antioxidant and protective potential against ion-mediated oxidative damage and may be considered as a potential drug against metal-mediated toxicity.


Assuntos
Antioxidantes/metabolismo , Sequestradores de Radicais Livres/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Especiarias , Xylopia/química , Camarões , Células Cultivadas/efeitos dos fármacos , Sequestradores de Radicais Livres/metabolismo , Casca de Planta/química , Extratos Vegetais/metabolismo , Extratos Vegetais/farmacologia
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