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1.
Biomol Biomed ; 24(1): 82-88, 2024 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-37289437

RESUMO

Teucrium polium (germander, Lamiaceae) is a local plant in Qatar that has been used in folk medicine to treat numerous illnesses. It is known for its antioxidant, analgesic, anticancer, and antibacterial activities. This study aimed to evaluate the anti-inflammatory activity of Teucrium polium (TP) extract by α-carrageen-induced paw edema in adult Sprague Dawley rats. The animals were randomly grouped into control, acute inflammation, and plant extract groups. Acute inflammation was induced by a sub-plantar injection of 100 µL of 1% α-carrageenan into the rat's right hind paw. Three different doses of the ethanolic extract of TP were tested at different time periods (1, 3, and 5 hours). All doses of the TP ethanolic extract showed significant inhibition of α-carrageenan-induced rat paw edema in a dose-dependent manner in both early and late phases of edema formation. The size of the α-carrageen induced paw edema was significantly reduced one, three, and five hours after TP extract injection compared to the acute inflammation group. This inhibition was accompanied by high expression of interleukin 10 (IL-10) and low expression of monocyte chemoattractant protein 1 (MCP-1), IL-1ß and tumor necrosis factor alpha (TNF-α). The results indicated that the ethanolic extracts of TP possess significant anti-inflammatory and potential pharmaceutical properties.


Assuntos
Teucrium , Ratos , Animais , Carragenina/toxicidade , Ratos Sprague-Dawley , Extratos Vegetais/farmacologia , Anti-Inflamatórios/farmacologia , Inflamação/induzido quimicamente , Edema/induzido quimicamente
2.
Nutrients ; 16(1)2023 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-38201945

RESUMO

Consumption of a high-carbohydrate diet has a critical role in the induction of weight gain and obesity-related pathologies. This study tested the hypothesis that a carbohydrate-rich diet induces weight gain, ectopic fat deposition, associated metabolic risks and development of non-alcoholic fatty liver disease (NAFLD), which are partially reversible following carbohydrate reduction. Sprague Dawley (SD) rats were fed a carbohydrate-enriched cafeteria diet (CAF) or normal chow (NC) ad libitum for 16-18 weeks. In the reversible group (REV), the CAF was replaced with NC for a further 3 weeks (18-21 weeks). Animals fed the CAF diet showed significantly increased body weight compared to those fed NC, accompanied by abnormal changes in their systemic insulin and triglycerides, elevation of hepatic triglyceride and hepatic steatosis. In the REV group, when the CAF diet was stopped, a modest, non-significant weight loss was associated with improvement in systemic insulin and appearance of the liver, with lower gross fatty deposits and hepatic triglyceride. In conclusion, a carbohydrate-enriched diet led to many features of metabolic syndrome, including hyperinsulinemia, while a dietary reduction in this macronutrient, even for a short period, was able to restore normoinsulinemia, and reversed some of the obesity-related hepatic abnormalities, without significant weight loss.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Ratos , Animais , Hepatopatia Gordurosa não Alcoólica/etiologia , Ratos Sprague-Dawley , Dieta/efeitos adversos , Obesidade/etiologia , Aumento de Peso , Insulina , Triglicerídeos , Redução de Peso , Carboidratos
3.
Int J Mol Sci ; 23(19)2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-36232443

RESUMO

Impaired adipogenesis is associated with the development of insulin resistance and an increased risk of type 2 diabetes (T2D). GATA Binding Protein 3 (GATA3) is implicated in impaired adipogenesis and the onset of insulin resistance. Therefore, we hypothesize that inhibition of GATA3 could promote adipogenesis, restore healthy fat distribution, and enhance insulin signaling. Primary human preadipocytes were treated with GATA3 inhibitor (DNAzyme hgd40). Cell proliferation, adipogenic capacity, gene expression, and insulin signaling were measured following well-established protocols. BALB/c mice were treated with DNAzyme hgd40 over a period of 2 weeks. Liposomes loaded with DNAzyme hgd40, pioglitazone (positive), or vehicle (negative) controls were administered subcutaneously every 2 days at the right thigh. At the end of the study, adipose tissues were collected and weighed from the site of injection, the opposite side, and the omental depot. Antioxidant enzyme (superoxide dismutase and catalase) activities were assessed in animals' sera, and gene expression was measured using well-established protocols. In vitro GATA3 inhibition induced the adipogenesis of primary human preadipocytes and enhanced insulin signaling through the reduced expression of p70S6K. In vivo GATA3 inhibition promoted adipogenesis at the site of injection and reduced MCP-1 expression. GATA3 inhibition also reduced omental tissue size and PPARγ expression. These findings suggest that modulating GATA3 expression offers a potential therapeutic benefit by correcting impaired adipogenesis, promoting healthy fat distribution, improving insulin sensitivity, and potentially lowering the risk of T2D.


Assuntos
DNA Catalítico , Diabetes Mellitus Tipo 2 , Resistência à Insulina , Adipogenia/genética , Animais , Antioxidantes/uso terapêutico , Catalase , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Insulina/uso terapêutico , Resistência à Insulina/genética , Lipossomos/uso terapêutico , Camundongos , Obesidade/metabolismo , PPAR gama/metabolismo , Pioglitazona/uso terapêutico , Proteínas Quinases S6 Ribossômicas 70-kDa , Superóxido Dismutase
4.
Front Pharmacol ; 13: 1010817, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36278208

RESUMO

Cadmium (Cd) is a widespread heavy metal known as a toxic environmental pollutant. Cd exposure is threatening due to its bioaccumulation trait in living systems that exceeds 35 years without a beneficial biological role. Acute exposure to high Cd doses was reported to impact adipose tissue (AT) function adversely. The main aim of this study is to investigate the effect of low-dose chronic Cd exposure on the genes involved in adipose tissue (AT) functions. Adult male Sprague-Dawley rats were exposed to a low Cd dose (15 mg/kg B.W./day) for 10 weeks. Then, three AT depots-subcutaneous AT (SUB-AT), abdominal AT (AB-AT), and retroperitoneal AT (REtrop-AT) were excised for Cd accumulation measures and gene expression analysis. Adiponectin and leptin gene expression levels were investigated as markers for adipocytes function and homeostasis. Our results showed that Cd accumulated in all the tested adipose depots, but SUB-AT was found to be the depot to most accumulate Cd. Also, it was exhibited that chronic exposure to low Cd doses altered the gene expression of adipocytokines. The levels of adiponectin and leptin mRNA expression were downregulated in all tested AT-depots after Cd exposure. The significant adverse effect on SUB-AT compared to other depots indicates different responses based on AT depots location toward Cd exposure. Collectively, these results suggest a toxic effect of Cd that influenced adipocyte function.

5.
Mol Nutr Food Res ; : e2200322, 2022 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-36156389

RESUMO

SCOPE: The composition of the gut microbiota is influenced by the dietary nutrient. Sugar has been linked with many metabolic health disorders such as heart disease, metabolic syndrome, and immune disorders. Long-term consumption of sugar influences the landscape of gut microbiota by altering the gut microbial population called dysbiosis. This study aims to evaluate the impact of long-term consumption of high sugar diet (HSD) on the diversity of gut microbiota. METHODS AND RESULTS: CD1 mice are given high concentration of sugar for 15 weeks followed by a recovery period of 10 weeks. Real-time polymerase chain reaction and 16S rRNA next-generation sequencing methods employ to identify microbiome diversity. The results show that Firmicutes and Bacteroidetes are the predominant phyla in control, cecum, and fecal samples. Firmicutes population are gradually increased in treated samples even after the recovery period, whereas Bacteroidetes abundance slightly reduces throughout the study. CONCLUSION: The present study shows that the impact of long period of high sugar diet consumption alters the diversity of normal gut flora which can be restored after 10 weeks of sugar withdrawal. This indicates that the intervention of healthy and nutritious diet influences gut microbes and this can be beneficial in reducing the implication of early life metabolic disorders such as obesity.

6.
Front Pharmacol ; 12: 663048, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34447306

RESUMO

The aim of this study was to evaluate the role of chronic cadmium exposure in modulating cardiac matrix metalloproteinases (MMPs) in the heart of rats. Adult male Sprague-Dawley rats were exposed to 15 ppm CdCl2 in drinking water for 10 weeks followed by withdrawal of cadmium treatment for 4 weeks. Following the completion of the treatment, gene expression of inflammatory mediators (IL-1ß, IL-6, IL-10, TNF-α and NF-κB), protein expression of MMP-2, MMP-9 and their respective inhibitors- TIMP-1 and TIMP-2, and gelatinolytic activity of MMP-2 and MMP-9 were determined. At the protein level, cadmium incites a differential effect on the expression and activity of gelatinases and their endogenous inhibitors in an exposure-dependent manner. Results also show that the administered cadmium dose elicits an inflammatory response until week 10 that slightly diminishes after 4 weeks. This study provides evidence of cadmium-induced imbalance in the MMP-TIMP system in the cardiac tissue. This imbalance may be mediated by cadmium-induced inflammation that could contribute to various cardiovascular pathologies.

7.
Environ Sci Pollut Res Int ; 27(14): 16246-16253, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32124290

RESUMO

Cadmium (Cd) is a naturally occurring toxic heavy metal with no known essential biological functions. Exposure to Cd increases the risk of cardiovascular disease by disrupting vascular homeostasis at the endothelium. The aim of the study was to evaluate the effect of chronic low-dose Cd on vascular structure and function. Fifty adult male Sprague Dawley rats were grouped and assigned to one of two treatments for 14 weeks. The control group received normal water for 14 weeks while the Cd-treated group received 15 mg Cd/kg B.W. as CdCl2 in water for 10 weeks. A subset of the Cd-treated group received 15 mg Cd/kg B.W. as CdCl2 in water for 10 weeks followed by 4 weeks of normal water. Results show an overall decline in vascular function and structure. Withdrawal of Cd treatment showed a considerable restoration of vascular structure and vasorelaxation function. Additionally, asymmetric dimethylarginine (ADMA) bioavailability was found to be lowered over time. Interestingly, the expression of eNOS in the Cd-treated group was found to be significantly elevated during the exposure by more than 3-fold in comparison with that in the control group. This protein expression was similar to the control group after the withdrawal of Cd treatment. Taken together, the results suggest that ADMA, an eNOS inhibitor, may play a role in altering endothelial function in the presence of cadmium. In conclusion, the findings indicate that even at low doses, Cd leads to endothelial dysfunction mediated by ADMA.


Assuntos
Cádmio , Endotélio Vascular , Animais , Arginina/análogos & derivados , Masculino , Óxido Nítrico , Ratos , Ratos Sprague-Dawley
8.
Semin Cancer Biol ; 54: 1-13, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29524560

RESUMO

Abnormally activated RAS proteins are the main oncogenic driver that governs the functioning of major signaling pathways involved in the initiation and development of human malignancies. Mutations in RAS genes and or its regulators, most frequent in human cancers, are the main force for incessant RAS activation and associated pathological conditions including cancer. In general, RAS is the main upstream regulator of the highly conserved signaling mechanisms associated with a plethora of important cellular activities vital for normal homeostasis. Mutated or the oncogenic RAS aberrantly activates a web of interconnected signaling pathways including RAF-MEK (mitogen-activated protein kinase kinase)-ERK (extracellular signal-regulated kinase), phosphoinositide-3 kinase (PI3K)/AKT (protein kinase B), protein kinase C (PKC) and ral guanine nucleotide dissociation stimulator (RALGDS), etc., leading to uncontrolled transcriptional expression and reprogramming in the functioning of a range of nuclear and cytosolic effectors critically associated with the hallmarks of carcinogenesis. This review highlights the recent literature on how oncogenic RAS negatively use its signaling web in deregulating the expression and functioning of various effector molecules in the pathogenesis of human malignancies.


Assuntos
Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , Transdução de Sinais , Proteínas ras/genética , Proteínas ras/metabolismo , Animais , Biomarcadores Tumorais , Regulação Neoplásica da Expressão Gênica , Frequência do Gene , Humanos , Imunomodulação/genética , Inflamação/genética , Inflamação/metabolismo , Terapia de Alvo Molecular , Mutação , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Oncogenes , Proteínas Quinases Associadas a Fase S/genética , Proteínas Quinases Associadas a Fase S/metabolismo , Relação Estrutura-Atividade , Fatores de Transcrição/metabolismo , Proteínas ras/química
9.
Front Physiol ; 9: 1942, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30728783

RESUMO

The ability of epithelial cells to organize through cell-cell adhesion into a functioning epithelium serves the purpose of a tight epithelial protective barrier. Contacts between adjacent cells are made up of tight junctions (TJ), adherens junctions (AJ), and desmosomes with unique cellular functions and a complex molecular composition. These proteins mediate firm mechanical stability, serves as a gatekeeper for the paracellular pathway, and helps in preserving tissue homeostasis. TJ proteins are involved in maintaining cell polarity, in establishing organ-specific apical domains and also in recruiting signaling proteins involved in the regulation of various important cellular functions including proliferation, differentiation, and migration. As a vital component of the epithelial barrier, TJs are under a constant threat from proinflammatory mediators, pathogenic viruses and bacteria, aiding inflammation and the development of disease. Inflammatory bowel disease (IBD) patients reveal loss of TJ barrier function, increased levels of proinflammatory cytokines, and immune dysregulation; yet, the relationship between these events is partly understood. Although TJ barrier defects are inadequate to cause experimental IBD, mucosal immune activation is changed in response to augmented epithelial permeability. Thus, the current studies suggest that altered barrier function may predispose or increase disease progression and therapies targeted to specifically restore the barrier function may provide a substitute or supplement to immunologic-based therapies. This review provides a brief introduction about the TJs, AJs, structure and function of TJ proteins. The link between TJ proteins and key signaling pathways in cell proliferation, transformation, and metastasis is discussed thoroughly. We also discuss the compromised intestinal TJ integrity under inflammatory conditions, and the signaling mechanisms involved that bridge inflammation and cancer.

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