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1.
Food Chem Toxicol ; 192: 114965, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39197524

RESUMEN

Metabolic dysfunction-associated steatotic liver disease (MASLD) is defined as morphofunctional changes in the liver. Studies have shown that Westernized eating patterns and environmental pollutants can directly induce the development of MASLD. This study evaluates the effect of co-exposure to interesterified palm oil (IPO) and 3,3',4,4',5-pentachlorobiphenyl (PCB-126) on the progression of MASLD in an animal model. C57BL/6 mice were fed IPO and co-exposed to PCB-126 for ten weeks. The co-exposure led to an imbalance in carbohydrate metabolism, increased systemic inflammation markers, and morphofunctional changes in the liver. These liver changes included the presence of inflammatory cells, fibrosis, alterations in aspartate transaminase (AST) and alanine transaminase (ALT) enzymes, and imbalance in gene expression related to fatty acid ß-oxidation, de novo lipogenesis, mitochondrial dynamics, and endoplasmic reticulum stress. Separate exposures to IPO and PCB-126 affected metabolism and MASLD progression. Nutritional and lifestyle factors may potentiate the onset and severity of MASLD.


Asunto(s)
Hígado , Ratones Endogámicos C57BL , Aceite de Palma , Bifenilos Policlorados , Animales , Bifenilos Policlorados/toxicidad , Ratones , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Hígado Graso/inducido químicamente , Hígado Graso/metabolismo , Estrés del Retículo Endoplásmico/efectos de los fármacos , Contaminantes Ambientales/toxicidad
2.
PLoS One ; 19(8): e0308334, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39133714

RESUMEN

Environmental pollutants, including polychlorinated biphenyls (PCBs), act as endocrine disruptors and impair various physiological processes. PCB 126 is associated with steatohepatitis, fibrosis, cirrhosis, and other hepatic injuries. These disorders can be regulated by microRNAs (miRNAs). Therefore, this study aimed to investigate the role of miRNAs in non-alcoholic fatty liver disease associated with exposure to PCB 126. Adult male C57BL/6 mice were exposed to PCB 126 (5 µmol/kg of body weight) for 10 weeks. The PCB group showed lipid accumulation in the liver in the presence of macro- and microvesicular steatosis and fibrosis with increased inflammatory and profibrotic gene expression, consistent with non-alcoholic steatohepatitis (NASH). PCB exposure also upregulated miR-155 and miR-34a, which induce the expression of proinflammatory cytokines and inflammation in the liver and reduce the expression of peroxisome proliferator-activated receptor α, which, in turn, impairs lipid oxidation and hepatic steatosis. Therefore, the present study showed that PCB 126 induced NASH via potential mechanisms involving miR-155 and miR-34a, which may contribute to the development of new diagnostic markers and therapeutic strategies.


Asunto(s)
Cirrosis Hepática , Ratones Endogámicos C57BL , MicroARNs , Bifenilos Policlorados , Regulación hacia Arriba , Animales , MicroARNs/genética , MicroARNs/metabolismo , Bifenilos Policlorados/toxicidad , Masculino , Ratones , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/genética , Cirrosis Hepática/metabolismo , Cirrosis Hepática/patología , Regulación hacia Arriba/efectos de los fármacos , Hígado/metabolismo , Hígado/efectos de los fármacos , Hígado/patología , Enfermedad del Hígado Graso no Alcohólico/inducido químicamente , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedad del Hígado Graso no Alcohólico/patología , Contaminantes Ambientales/toxicidad , Metabolismo de los Lípidos/efectos de los fármacos , Metabolismo de los Lípidos/genética
3.
J Nutr Biochem ; 117: 109336, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36990367

RESUMEN

This study aimed to evaluate the preventive and therapeutic effects of coffee consumption on molecular changes and adipose tissue remodeling in a murine model of high-fat diet-induced obesity. Three-month-old C57BL/6 mice were initially divided into three groups, namely, control (C), high-fat (HF), and coffee prevention (HF-CP) groups, and the HF group was subdivided at the end of the 10th week into two subgroups, an HF group and a coffee treatment (HF-CT) group; thus, a total of four groups were investigated at the 14th week of the experiment. The HF-CP group had lower body mass than the HF group (-7%, P < .05) and a better distribution of adipose tissue. Both groups that received coffee (HF-CP and HF-CT) showed improved glucose metabolism compared with the HF group. Coffee consumption also attenuated adipose tissue inflammation and showed decreased macrophage infiltration and lower IL-6 levels compared with the HF group (HF-CP: -337% %, P < .05; HF-CT: -275%, P < .05). Hepatic steatosis and inflammation were attenuated in the HF-CP and HF-CT groups. The HF-CP group showed more pronounced expression of genes involved in adaptive thermogenesis and mitochondrial biogenesis (PPARγ, Prdm16, Pcg1α, ß3-adrenergic receptor, Ucp-1, and Opa-1) than the other experimental groups. Preventive coffee consumption associated with a high-fat diet ameliorates the metabolic profile related to the development of obesity and its comorbidities.


Asunto(s)
Tejido Adiposo Pardo , Dieta Alta en Grasa , Ratones , Animales , Tejido Adiposo Pardo/metabolismo , Dieta Alta en Grasa/efectos adversos , Café , Ratones Endogámicos C57BL , Obesidad/metabolismo , Tejido Adiposo/metabolismo , Inflamación/metabolismo
4.
Anticancer Res ; 43(1): 359-367, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36585169

RESUMEN

BACKGROUND/AIM: Prostate cancer (PCa) is one of the most common malignancies in adult men. LQB-118 is a pterocarpanquinone with antitumor activity toward prostate cancer cells. It inhibits cell proliferation by down-regulating cyclins D1 and B1 and up-regulating p21. However, the effects of LQB-118 on PCa cell migration are still unclear. Herein, the LQB-118 effects on PCa metastatic cell migration/invasion and its mechanism of action were evaluated. MATERIALS AND METHODS: PC3 cells were treated with LQB-118 or Paclitaxel (PTX), and cell migration (wound healing and Boyden chamber assays) and invasion (matrigel assay) were determined. The LQB-118 mechanisms were evaluated by αVßIII protein expression (flow cytometry), protein phosphorylation (Western blot), and mRNA expression (qPCR). RESULTS: LQB-118 impaired PCa cell migration and invasion, down-regulated Akt phosphorylation, and also reduced GSK3ß phosphorylation, through a FAK-independent pathway. Also, it was observed that LQB-118 controlled the invasiveness behavior by reducing matrix metalloproteinase-9 (MMP-9) and up-regulating reversion-inducing cysteine rich protein with Kazal motifs (Reck) mRNA levels. Interestingly, LQB-118 increased integrin αvßIII expression, but this effect was not related to its activation, since the cell adhesion ability was reduced after LQB-118 treatment. CONCLUSION: These data highlight novel LQB-118 mechanisms in prostate cancer cells. LQB-118 acts as a negative regulator of the Akt/GSK3 signaling pathway and can modulate PCa cell proliferation, death, and migration/invasion. The results also support the use of LQB-118 for the treatment of metastatic PCa, alone or combined with another chemotherapeutic agent, due to its demonstrated pleiotropic activities.


Asunto(s)
Metaloproteinasa 9 de la Matriz , Neoplasias de la Próstata , Humanos , Masculino , Línea Celular Tumoral/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Expresión Génica , Glucógeno Sintasa Quinasa 3/genética , Glucógeno Sintasa Quinasa 3/farmacología , Glucógeno Sintasa Quinasa 3/uso terapéutico , Glucógeno Sintasa Quinasa 3 beta/efectos de los fármacos , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Proteínas Ligadas a GPI/efectos de los fármacos , Proteínas Ligadas a GPI/genética , Proteínas Ligadas a GPI/metabolismo , Metaloproteinasa 9 de la Matriz/efectos de los fármacos , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/metabolismo , Invasividad Neoplásica , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Proteínas Proto-Oncogénicas c-akt/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Mensajero
5.
J Pharm Pharmacol ; 72(12): 1921-1932, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32856322

RESUMEN

OBJECTIVES: Obesity is considered a risk factor for the development of non-alcoholic fatty liver disease (NAFLD). The hydroalcoholic extract obtained from the açai seed (ASE), rich in proanthocyanidins, has been shown a potential body weight regulator with antioxidant properties. This study aimed to investigate the therapeutic effect of ASE in obesity-associated NAFLD and compare it with Rosuvastatin. METHODS: Male C57BL/6 mice received a high-fat diet or standard diet for 12 weeks. The treatments with ASE (300 mg/kg per day) or rosuvastatin (20 mg/kg per day) began in the eighth week until the 12th week. KEY FINDINGS: Our data show that the treatments with ASE and rosuvastatin reduced body weight and hyperglycaemia, improved lipid profile and attenuated hepatic steatosis in HFD mice. ASE and Rosuvastatin reduced HMGCoA-Reductase and SREBP-1C and increased ABGC8 and pAMPK expressions in the liver. Additionally, ASE, but not Rosuvastatin, reduced NPC1L1 and increased ABCG5 and PPAR-α expressions. ASE and rosuvastatin increased SIRT-1 expression and antioxidant defence, although only ASE was able to decrease the oxidative damage in hepatic tissue. CONCLUSIONS: The therapeutic effect of ASE was similar to that of rosuvastatin in reducing dyslipidemia and hepatic steatosis but was better in reducing oxidative damage and hyperglycaemia.


Asunto(s)
Euterpe , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Hipolipemiantes/farmacología , Hígado/efectos de los fármacos , Enfermedad del Hígado Graso no Alcohólico/prevención & control , Obesidad/tratamiento farmacológico , Extractos Vegetales/farmacología , Rosuvastatina Cálcica/farmacología , Animales , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Dislipidemias/metabolismo , Dislipidemias/prevención & control , Euterpe/química , Hiperglucemia/metabolismo , Hiperglucemia/prevención & control , Hipolipemiantes/aislamiento & purificación , Metabolismo de los Lípidos/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Masculino , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/patología , Obesidad/etiología , Obesidad/metabolismo , Obesidad/patología , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/aislamiento & purificación , Semillas
6.
Prev Nutr Food Sci ; 25(1): 25-31, 2020 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-32292752

RESUMEN

This study investigated the protective effect of a Vitis vinifera L. grape skin extract (ACH09) on blood pressure, lipid profile, and oxidative status in spontaneously hypertensive rats (SHR). Systolic blood pressure (SBP), total cholesterol, triglyceride, and glucose levels, as well as oxidative damage and antioxidant activity in the plasma and kidney, were evaluated in four experimental groups: control Wistar rats (W-C) and SHR-C that received water, and Wistar rats and SHR treated with ACH09 (200 mg/kg/d) in drinking water for 12 weeks (W-ACH09 and SHR-ACH09, respectively). SBP increased in the SHR group compared with the W groups and the treatment with ACH09 prevented the development of hypertension. Plasma triglyceride and total cholesterol levels increased in SHR compared with W-C rats; these changes prevented by treatment with ACH09. Glucose levels did not differ between the groups. The SHR group had increased oxidative damage in plasma, as expressed by 2-thiobarbituric acid reactive substances (TBARS) levels, and this prevented by ACH09. Levels of TBARS in the kidneys were lower in the SHR-ACH09 group than in the SHR-C group. Further, ACH09 increased the superoxide dismutase activity in both the plasma and kidneys of both SHR and Wistar rats. These results suggest that ACH09 is protective against disruption of blood pressures, oxidant status, and lipid profile in SHR, and provide important evidence on the benefits of ACH09 on hypertension and associated cardiovascular complications.

7.
Exp Physiol ; 105(3): 542-551, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31876965

RESUMEN

NEW FINDINGS: What is the central question of this study? Does a polyphenol-rich extract from açaí have a potential role in preventing uraemic toxin-induced endothelial cell dysfunction? What is the main finding and its importance? Polyphenols from açaí prevented cell death, restored migratory capacity, protected from inflammation and contributed to the restoration of the antioxidant response in endothelial cells exposed to uraemic toxins. The protective role of açaí against toxic effects exerted by uraemic toxins presents a potential new therapeutic target in endothelial cells. ABSTRACT: In chronic kidney disease (CKD), progressive loss of kidney function results in the accumulation of protein-bound uraemic toxins such as p-cresyl sulfate (pCS) and indoxyl sulfate (IS). Among strategies to ameliorate the harmful actions of uraemic toxins, phenolic compounds have been extensively studied. The main goal of this work was to evaluate the antioxidant and anti-inflammatory actions of phenolic-rich açaí seed extract (ASE) in response to endothelial dysfunction induced by IS and pCS, in human umbilical vein endothelial cells (HUVECs). Cells were treated with ASE (10 µg ml-1 ) in the presence or absence of IS (61 µg ml-1 ) and pCS (40 µg ml-1 ). Cell viability, cell death, cell migratory capacity and inflammatory biomarker expression were evaluated. Cellular antioxidant response was measured through the activity and expression of antioxidant enzymes, and oxidative damage was evaluated. IS and pCS lowered cell viability, triggered cell death and lowered the migratory capacity in endothelial cells (P < 0.05). ASE prevented cell death and restored the migratory capacity in cells exposed to IS. Both toxins up-regulated pro-inflammatory cytokine expression, and ASE was able to beneficially counteract this effect. Tumour necrosis factor-α secretion was greater in uraemic toxin-treated cells and ASE reversed this phenomenon in cells treated with both toxins concomitantly (P < 0.05). With regard to the antioxidant response, superoxide dismutase expression was strikingly lower in cells treated with both toxins, and ASE inhibited this harmful effect (P < 0.05). From the results, we conclude that ASE exerted protective effects on inflammation and oxidative stress caused by uraemic toxins (particularly by IS) in human endothelial cells.


Asunto(s)
Euterpe/química , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Inflamación/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Polifenoles/farmacología , Sustancias Protectoras/farmacología , Antioxidantes , Biomarcadores/metabolismo , Muerte Celular/efectos de los fármacos , Células Cultivadas , Citocinas/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Inflamación/metabolismo , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/metabolismo , Superóxido Dismutasa/metabolismo
8.
Eur J Prev Cardiol ; 21(10): 1225-32, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23695648

RESUMEN

BACKGROUND: Heart failure (HF) patients are at an increased risk of thrombotic events. Here, we investigated the effects of exercise training on platelet function and factors involved in its modulation in HF. DESIGN AND METHODS: Thirty HF patients were randomized to 6 months of supervised exercise training or to a control group that remained sedentary. Exercise training consisted of 30 min of moderate-intensity treadmill exercise, followed by resistance and stretching exercises, performed three times a week. Blood was collected before and after the intervention for platelet and plasma obtainment. RESULTS: Peak VO2 increased after exercise training (18.0 ± 2.2 vs. 23.8 ± 0.5 mlO2/kg/min; p < 0.05). Exercise training reduced platelet aggregation induced by both collagen and ADP (approximately -6%; p < 0.05), as well as platelet nitric oxide synthase activity (0.318 ± 0.030 vs. 0.250 ± 0.016 pmol/10(8) cells; p < 0.05). No difference in the above-mentioned variables were observed in the control group. No significant difference was observed in intraplatelet cyclic guanosine monophosphate levels among groups. There was a significant increase in the activity of the antioxidant enzymes superoxide dismutase and catalase in plasma and platelets, resulting in a decrease in both lipid and protein oxidative damage. Systemic levels of the inflammatory markers C-reactive protein, fibrinogen, and tumour necrosis factor α were also reduced in HF after training. CONCLUSIONS: Our results suggest that regular exercise training is a valuable adjunct to optimal medical management of HF, reducing platelet aggregation via antioxidant and anti-inflammatory effects, and, therefore, reducing the risk of future thrombotic events.


Asunto(s)
Antioxidantes/metabolismo , Terapia por Ejercicio/métodos , Insuficiencia Cardíaca/terapia , Mediadores de Inflamación/sangre , Inflamación/prevención & control , Estrés Oxidativo , Agregación Plaquetaria , Trombosis/prevención & control , Biomarcadores/sangre , Plaquetas/enzimología , Plaquetas/inmunología , Brasil , GMP Cíclico/sangre , Femenino , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/inmunología , Humanos , Inflamación/sangre , Inflamación/inmunología , Lípidos/sangre , Masculino , Persona de Mediana Edad , Actividad Motora , Ejercicios de Estiramiento Muscular , Óxido Nítrico Sintasa/sangre , Consumo de Oxígeno , Pruebas de Función Plaquetaria , Valor Predictivo de las Pruebas , Estudios Prospectivos , Recuperación de la Función , Entrenamiento de Fuerza , Factores de Riesgo , Trombosis/sangre , Trombosis/diagnóstico , Factores de Tiempo , Resultado del Tratamiento
9.
Hypertens Res ; 33(9): 899-904, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20555333

RESUMEN

Nitric oxide (NO) is a short-lived intercellular messenger that provides an efficient vascular regulatory mechanism to support homeostasis and prevent thrombosis. Endothelial dysfunction and reduced NO bioavailability have a central role in hypertension associated with pregnancy. The purpose of this study was to investigate the impact of pregnancy on the L-arginine-NO-cGMP pathway in platelets and its correlation to platelet function and blood pressure in normotensive rats and spontaneously hypertensive rats (SHRs). Platelets were obtained from blood on the 20th day of pregnancy from female SHRs (SHR-P) and normotensive controls (P) or age-matched nonpregnant rats (SHR-NP and NP). Intraplatelet NO synthase (NOS) activity was reduced in P compared to NP, despite unchanged L-arginine influx. The expression levels of endothelial NOS (eNOS) and inducible NOS (iNOS) were diminished during pregnancy in normotensive rats. Paradoxically, cyclic guanosine monophosphate (cGMP) levels were similar between NP and P, as were phosphodiesterase type 5 (PDE5) expression and platelet aggregation induced by adenosine diphosphate. In SHRs, L-arginine influx was reduced in SHR-P compared to SHR-NP. SHR-P exhibited impaired NOS activity and reduced iNOS expression compared with SHR-NP. Soluble guanylyl cyclase and PDE5 expression in platelets were lower in SHR-P than in SHR-NP, whereas no differences were noted between groups with respect to cGMP levels. However, increased levels of cGMP were observed in SHR-P compared to normotensive groups and platelet aggregability remained unaltered. In conclusion, these observations prompted the hypothesis that normal platelet aggregation in pregnant SHRs may be related to a reduction in PDE5 expression and consequently the maintenance of cGMP levels, independently of reduced platelet NO bioavailability.


Asunto(s)
Arginina/metabolismo , GMP Cíclico/metabolismo , Hipertensión/metabolismo , Óxido Nítrico/metabolismo , Animales , Arginina/fisiología , Plaquetas/enzimología , GMP Cíclico/análisis , GMP Cíclico/fisiología , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 5/análisis , Femenino , Guanilato Ciclasa/análisis , Hipertensión/fisiopatología , Óxido Nítrico/fisiología , Óxido Nítrico Sintasa/análisis , Óxido Nítrico Sintasa de Tipo II/análisis , Óxido Nítrico Sintasa de Tipo III/análisis , Agregación Plaquetaria , Embarazo , Ratas , Ratas Endogámicas SHR , Ratas Wistar
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