21 results on '"Gómez‐Zamudio, J."'
Search Results
2. Adventitia removal does not modify the α1D-adrenoceptors response in aorta during hypertension and ageing
- Author
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Gómez-Zamudio, J. H. and Villalobos-Molina, R.
- Published
- 2009
- Full Text
- View/download PDF
3. Selective agonists reveal α1A- and α1B-adrenoceptor subtypes in caudal artery of the young rat
- Author
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Parés-Hipólito, J., Gómez-Zamudio, J. H., Gallardo-Ortiz, I. A., López-Guerrero, J. J., Santamaría-Ortiz, J., Ibarra, M., and Villalobos-Molina, R.
- Published
- 2006
4. Chloroethylclonidine reveals that α1A-adrenoceptors mediate contraction in aorta of α1D-adrenoceptor knockout mice
- Author
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Lázaro-Suárez, M. L., Gómez-Zamudio, J. H., Gallardo-Ortíz, I. A., Tanoue, A., Tsujimoto, G., Farias-Rodríguez, V. M., and Villalobos-Molina, R.
- Published
- 2005
5. APOA5 and APOA1 polymorphisms are associated with triglyceride levels in Mexican children
- Author
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Suárez-Sánchez, F., primary, Klunder-Klunder, M., additional, Valladares-Salgado, A., additional, Gómez-Zamudio, J., additional, Peralta-Romero, J., additional, Meyre, D., additional, Burguete-García, A., additional, and Cruz, M., additional
- Published
- 2016
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6. APOA5 and APOA1 polymorphisms are associated with triglyceride levels in Mexican children.
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Suárez‐Sánchez, F., Klunder‐Klunder, M., Valladares‐Salgado, A., Gómez‐Zamudio, J., Peralta‐Romero, J., Meyre, D., Burguete‐García, A., and Cruz, M.
- Subjects
DNA ,GENETIC polymorphisms ,GLUCOSE ,HYPERLIPIDEMIA ,LIPIDS ,TRIGLYCERIDES ,DATA analysis software ,DESCRIPTIVE statistics - Abstract
Background Dyslipidemia is an important risk factor for the development of several diseases. The genetic component of hypertriglyceridemia has been studied in adults, but little is known in children. Objective The objective is to evaluate the association of two variants in APOA5 (rs662799) and APOA1 (rs5072) with triglyceride (TG) levels in Mexican children. Methods Anthropometric parameters were measured in 1559 Mexican children 5-14 years of age. DNA was isolated from blood samples. Lipid profiles and glucose concentrations were determined from serum and genotyping of rs662799, and rs5072 was performed using TaqMan® technology. Additive and dominant models adjusted for age, gender and body mass index were used to evaluate the association of these single nucleotide polymorphisms with TG levels. Results Children with high TG levels were found to have a higher body mass index and waist circumference as well as a worse lipids profile and glucose levels ( p < 0.001). Additive and dominant models demonstrated a significant association between the rs662799 and rs5072 with TG. The dominant model showed the strongest significant association (OR = 1.81; 95% CI 1.46-2.24; p = 5.40 × 10
−08 for rs662799 and OR = 1.54; 95% CI 1.05-2.25; p = 2.60 × 10−02 for rs5072). Conclusion The minor alleles of rs662799 ( APOA5) and rs5072 ( APOA1) modulate TG levels in Mexican children. [ABSTRACT FROM AUTHOR]- Published
- 2017
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7. Angiotensin II modifies the expression of α1-adrenoceptors in aorta smooth muscle cells of α1D-adrenoceptor knockout mice.
- Author
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Lázaro-Suárez, M. L., Gómez-Zamudio, J. H., Delgado-Buenrostro, N. L., Tanoue, A., Tsujimoto, G., and Villalobos-Molina, R.
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ANGIOTENSIN II , *GENE expression , *SMOOTH muscle , *LABORATORY mice , *ADRENERGIC receptors , *MESSENGER RNA , *WESTERN immunoblotting - Abstract
Summary 1 The effect of angiotensin II (Ang II) on α1A-, α1B-, and a1D-adrenoceptors (α1-AR) expression was analyzed in aorta smooth muscle cells obtained from wild-type (WT) and knock out of α1D-AR (α1D-AR KO) mice. 2 The relative abundance of mRNA for the three α1-ARs was determined in WT and α1D-AR KO aortic smooth muscle cells. There were no significant differences between WT and α1D-AR KO cells. 3 As early as 1 h Ang II increased α1B-AR mRNA in WT cells ≈ 2 fold compared with control; in contrast, in α1D-AR KO cells the α1B-AR transcript was ≈ 50% of control. 4 Western blot assays showed that Ang II incremented protein content for α1A-AR, 86% and 107% in WT and α1D-AR KO cells, respectively. 5 Protein for α1B- and α1D-ARs did not change significantly with Ang II in both WT and a1D-AR KO cells. 6 The effect of Ang II on α1B-AR mRNA seems to be influenced by the absence of α1D-AR in aortic smooth muscle cells, which might be important to understand the interactions among α1-ARs. [ABSTRACT FROM AUTHOR]
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- 2011
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8. Adventitia removal does not modify the α1D-adrenoceptors response in aorta during hypertension and ageing.
- Author
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Gómez-Zamudio, J. H. and Villalobos-Molina, R.
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GENETICS of aging , *MURIDAE , *DEVELOPMENTAL biology , *RATS , *ANIMAL models in research , *BLOOD circulation disorders ,AGE factors in hypertension - Abstract
1 The aim of the current study was to characterize the α1-adrenergic receptors (α1-ARs) present in the isolated tunica media of aorta, in normotensive Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats during the course of ageing and hypertension (rats of 1, 3, 6 and 12 months of age). In all vessels, endothelium was removed. 2 In isolated aortic rings, phenylephrine increased contraction in a concentration- and age-dependent manner and was impaired in old SHR compared with WKY rats. 3 The α1-AR selective antagonist prazosin showed high affinity (p A2) in vessels from both rat strains. 4 The potency of the α1A-AR selective antagonists, RS 100329 (5-methyl-3-[3-[4-[2-(2,2,2,-trifluoroethoxy) phenyl]-1-piperazinyl] propyl]-2,4-(1H)-pyrimidinedione) and 5-methylurapidil in antagonizing aortic phenylephrine-responses was low. 5 The α1D-AR selective antagonist, BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1 piperazynil] ethyl]-8-azaspiro [4.5] decane-7,9-dione) potently blocked phenylephrine-induced responses in aorta from both strains and at all ages. 6 Adventitia removal decreased Emax in older rats and modified the relative affinity (p D2), but did not affect the affinity of the selective antagonists. 7 The results suggest that aorta tunica α1D-AR is the main subtype involved in phenylephrine-induced contraction of rat aorta, while α1A-AR plays only a minor role. 8 Ageing and hypertension did not modify α1-ARs in the blood vessel and the tunica adventitia does not seem to participate in contraction, even though α1-ARs are expressed. [ABSTRACT FROM AUTHOR]
- Published
- 2009
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9. Chloroethylclonidine reveals that α1A-adrenoceptors mediate contraction in aorta of α1D-adrenoceptor knockout mice.
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Lázaro-Suárez, M. L., Gómez-Zamudio, J. H., Gallardo-Ortíz, I. A., Tanoue, A., Tsujimoto, G., Farias-Rodríguez, V. M., and Villalobos-Molina, R.
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ADRENERGIC receptors , *AORTA , *DRUG receptors , *SYMPATHETIC nervous system , *MICE , *PHARMACOLOGY - Abstract
1 We have characterized the α1-adrenoceptor subtypes present in isolated aorta of the α1D-adrenoceptor knockout (KO) mice, by chloroethylclonidine (CEC)-induced alkylation and their protection by selective α1-adrenoceptor antagonists. 2 The α1D-adrenoceptor is involved in the contractile response to noradrenaline in wild type (WT) mouse aorta. 3 In WT mice 5-methylurapidil (5-MU, an α1A-adrenoceptor antagonist) or BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl] ethyl]-8-azaspiro[4.5] decane-7,9 dione, a selective α1D-adrenoceptor antagonist), protected the receptors from CEC-induced ( α1B/D-adrenoceptor) alkylation, the combination of both antagonists resulted in complete protection, while AH11110A (1-[biphenyl-2-yloxy]-4-imino-4-piperidin-1-yl-butan-2-ol, an α1B-adrenoceptor antagonist) did not protect. 4 In aorta of KO mice there was a 19-fold rightward shift in noradrenaline effective concentration (EC50) compared with WT; while 5-MU alone or in combination with AH11110A protected α1-adrenoceptors to the same extent. 5 The data indicate that α1A-adrenoceptors mediate contraction and suggest their role in maintaining homeostasis in the α1D-adrenoceptors KO mice. [ABSTRACT FROM AUTHOR]
- Published
- 2005
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10. Level of expression of gene CTSL and its correlation with natural killer T-cells in Mexican pediatric patients with recent-onset type 1 diabetes,Asociación de células NKT con la expresión del gen CTSL en población pediátrica Mexicana con diabetes tipo 1 de reciente diagnostic
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Gómez-Díaz, R. A., Medina-Santillán, R., Castro-Magdonel, B. E., Bekker-Méndez, C., Gómez-Zamudio, J., Nishimura-Meguro, E., Garrido-Magaña, E., Lizárraga-Paulin, L., Aguilar-Herrera, B. E., Valladares-Salgado, A., Miguel Cruz Lopez, Mondragón-González, R., Ortiz-Navarrete, V., and Wacher, N. H.
11. Genetics of pediatric obesity,Genética de la obesidad infantil
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Peralta-Romero, Jd E. J., Gómez-Zamudio, J. H., Estrada-Velasco, B., Roberto Karam-Araujo, and Cruz-López, M.
12. PPARα/γ, adiponectin, and GLUT4 overexpression induced by moronic acid methyl ester influenced glucose and triglyceride levels of experimental diabetic mice.
- Author
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Estrada-Soto S, Cerón-Romero L, Navarrete-Vázquez G, Rosales-Ortega E, Gómez-Zamudio J, Cruz M, and Villalobos-Molina R
- Subjects
- Adiponectin metabolism, Animals, Blood Glucose metabolism, Esters therapeutic use, Glucose, Glucose Transporter Type 4 genetics, Hypoglycemic Agents chemistry, Hypoglycemic Agents pharmacology, Hypoglycemic Agents therapeutic use, Male, Mice, Oleanolic Acid analogs & derivatives, PPAR gamma metabolism, Triglycerides, Diabetes Mellitus, Experimental metabolism, PPAR alpha metabolism
- Abstract
The current study aimed to determine the antidiabetic and antidyslipidemic activities of moronic acid methyl ester (1) (compound 1 ) by in vivo, in vitro, in silico, and molecular biology studies. Compound 1 was evaluated to establish its dose-dependent antidiabetic and antihyperglycemic (50 mg/kg) activities, in diabetic and normoglycemic male CD1 mice, respectively. Also, compound 1 was subjected to a subacute study (50 mg/kg per day for 8 days) to determine blood biochemical profiles and the expression of protein tyrosine phosphatase 1B ( PTP-1B ), glucose transporter type 4 ( GLUT4 ), peroxisome proliferator-activated receptor α ( PPAR-α ), PPAR-γ , adiponectin, interleukin-1β (IL-1β), and monocyte chemoattractant protein 1 (MCP-1) in adipose tissue of animals after treatment. Different doses in acute administration of compound 1 decreased glycemia ( p < 0.05) compared with vehicle, showing greater effectiveness in the range 50-160 mg/kg. Also, the oral glucose tolerance test showed that compound 1 induced a significant antihyperglycemic action by opposing the hyperglycemic peak ( p < 0.05). Moreover, compound 1 subacute administration decreased glucose and triglyceride levels after treatment ( p < 0.05); while the expression of PPAR-α and PPAR-γ, adiponectin, and GLUT4 displayed an increase ( p < 0.05) compared with the diabetic control group. In conclusion, compound 1 showed antihyperglycemic, antidiabetic, and antidyslipidemic effects in normal and diabetic mice, probably due to insulin sensitization through increased mRNA expression of GLUT4 , PPAR-α , PPAR-γ , and adiponectin genes.
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- 2022
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13. Expression of obesity- and type-2 diabetes-associated genes in omental adipose tissue of individuals with obesity.
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Molina-Ayala MA, Rodríguez-Amador V, Suárez-Sánchez R, León-Solís L, Gómez-Zamudio J, Mendoza-Zubieta V, Cruz M, and Suárez-Sánchez F
- Subjects
- Adult, Bariatric Surgery, Cyclin D2 genetics, Female, Gene Expression, Humans, Male, Middle Aged, Obesity surgery, PTEN Phosphohydrolase genetics, Phenotype, Receptors, Interleukin-1 Type I genetics, Vascular Endothelial Growth Factor A genetics, Adipose Tissue physiology, Diabetes Mellitus, Type 2 genetics, Obesity genetics
- Abstract
Aims: Obesity and type 2 diabetes mellitus are two pathologies that share metabolic abnormalities in most of the cases; however, there are differences as well. Some studies have reported that approximately 30% of obese patients have normal glucose and lipid levels in blood despite an accumulation of abdominal adipose tissue. Here, we compare the gene expression in adipose tissue of several genes associated with obesity and/or diabetes between obese patients without T2D and obese patients with T2D., Methods: Omental adipose tissue was collected during the patients elective bariatric surgery. Gene expression was determined by real-time PCR. Phenotypic variables were correlated with gene expression and 2^
-ΔΔCt relative expression analysis between groups was performed., Results: The stronger correlations in the obese without T2D or reference group was between ICAM1 and HbA1c; HP and TC and LDL while in the obese with diabetes or case group the correlation occurred between CSF1 and BMI. A correlation between HP and TC was found in the case group as well. The expression of VEGFA, CCND2, IL1R1 and PTEN was downregulated in the obese with T2D group., Conclusions: This study identified genes whose expression is different between obese subjects with and without diabetes. Those genes are related to inflammation, cholesterol transport, adipocyte differentiation/expansion and browning., (Copyright © 2022 Elsevier B.V. All rights reserved.)- Published
- 2022
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14. Analysis of Flavonoids Bioactivity for Cholestatic Liver Disease: Systematic Literature Search and Experimental Approaches.
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Sánchez-Salgado JC, Estrada-Soto S, García-Jiménez S, Montes S, Gómez-Zamudio J, and Villalobos-Molina R
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- Animals, Flavonoids analysis, Humans, Cholestasis drug therapy, Flavonoids therapeutic use, Liver Diseases drug therapy
- Abstract
Flavonoids are naturally occurring compounds that show health benefits on the liver. However, there is little investigation about identification and evaluation of new flavonoid-containing drugs for cholestatic liver disease, one of the most common liver illnesses. We aimed to a systematic search regarding efficacy of flavonoids for treatment of cholestatic liver disease, and then evaluate naringenin (NG) as representative flavonoid in an obstructive cholestasis model. We searched for information of experimental and clinical studies in four major databases without time and language limits. Intervention was defined as any flavonoid derivate compared with other flavonoid, placebo, or without comparator. In addition, we evaluated NG on a bile duct-ligated model in order to contribute evidence of its actions. Eleven experimental reports that support the efficacy of flavonoids in cholestatic liver disease were identified. However, there was no homogeneity in efficacy endpoints evaluated and methodology. On the other hand, NG showed beneficial effects by improving specific metabolic (cholesterol and lipoproteins) and liver damage (bilirubin and alkaline phosphatase) biomarkers. The review lacks homogeneous evidence about efficacy of flavonoids in experimental settings, and is susceptible to risk for bias. NG only showed improvements in specific disease biomarkers. More investigation is still needed to determine its potential for drug development.
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- 2019
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15. Antidiabetic, antidyslipidemic and toxicity profile of ENV-2: A potent pyrazole derivative against diabetes and related diseases.
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Hernández-Vázquez E, Ocampo-Montalban H, Cerón-Romero L, Cruz M, Gómez-Zamudio J, Hiriart-Valencia G, Villalobos-Molina R, Flores-Flores A, and Estrada-Soto S
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- Adipose Tissue drug effects, Adipose Tissue metabolism, Animals, Body Weight drug effects, Diabetes Mellitus, Experimental complications, Gene Expression Regulation drug effects, Glucose Tolerance Test, Hydrazones therapeutic use, Hydrazones toxicity, Hypoglycemic Agents therapeutic use, Hypoglycemic Agents toxicity, Hypolipidemic Agents therapeutic use, Hypolipidemic Agents toxicity, Liver drug effects, Liver metabolism, Liver pathology, Male, Mice, Organ Size drug effects, Pyrazoles therapeutic use, Pyrazoles toxicity, Rats, Diabetes Mellitus, Experimental drug therapy, Hydrazones chemistry, Hydrazones pharmacology, Hypoglycemic Agents chemistry, Hypoglycemic Agents pharmacology, Hypolipidemic Agents chemistry, Hypolipidemic Agents pharmacology, Pyrazoles chemistry, Pyrazoles pharmacology
- Abstract
Diabetes is a major health problem and a predisposition factor for further degenerative complications and, therefore, novel therapies are urgently needed. Currently, cannabinoid receptor 1 (CB
1 receptor) antagonists have been considered as promissory entities for metabolic disorders treatment. Accordingly, the purpose of this work was the evaluation of the sub-acute antidiabetic, anti-hyperglycemic, antidyslipidemic and toxicological profile of ENV-2, a potent hypoglycemic and antioxidant CB1 receptor antagonist. In this study, ENV-2 showed a pronounced anti-hyperglycemic effect even at a dose of 5mg/kg (P<0.05) in a glucose tolerance test on normoglycemic rats. Moreover, after administration of ENV-2 (16mg/kg) to diabetic rats, a prominent antidiabetic activity was observed (P<0.05), which was higher than glibenclamide. Sub-acute treatment (10 days) of ENV-2 resulted in a significant reduction of plasma glucose (P<0.05). Also, the levels of peripheral lipids were improved; blood triacylglycerols (TG) and cholesterol (CHOL) were diminished (P<0.05). In addition, it was found that ENV-2 reduced IL-1β and IL-18 mRNA expression in adipose tissue (P<0.05). Due to the satisfactory outcomes, we were interested in evaluating the toxicity of ENV-2 in both acute and sub-chronic approaches. Regarding the acute administration, the compound resulted to be non-toxic and was grouped in category 5 according to OECD. It was also found that sub-chronic administration did not increase the size of the studied organs, while no structural damage was observed in heart, lung, liver and kidney tissues. Finally, neither AST nor ALT damage hepatic markers were augmented., (Copyright © 2017 Elsevier B.V. All rights reserved.)- Published
- 2017
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16. [Level of expression of gene CTSL and its correlation with natural killer T-Cells in mexican pediatric patients with recent-onset type 1 diabetes].
- Author
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Gómez-Díaz RA, Medina-Santillán R, Castro-Magdonel BE, Bekker-Méndez C, Gómez-Zamudio J, Nishimura-Meguro E, Garrido-Magaña E, Lizárraga-Paulin L, Aguilar-Herrera BE, Valladares-Salgado A, Cruz M, Mondragón-González R, Ortiz-Navarrete V, and Wacher NH
- Subjects
- Adolescent, Case-Control Studies, Child, Child, Preschool, Cross-Sectional Studies, Diabetes Mellitus, Type 1 blood, Diabetes Mellitus, Type 1 immunology, Female, Glycated Hemoglobin analysis, Humans, Lymphocyte Count, Male, Cathepsin L genetics, Diabetes Mellitus, Type 1 genetics, Natural Killer T-Cells cytology, Siblings
- Abstract
Objective: To compare the level of expression of the gene CTSL and its correlation with NKT cells in patients with recent-onset type 1 diabetes (T1D), their siblings, and healthy controls., Methods: Analytical cross-sectional design. Patients with T1D < 3 months evolution, their siblings, and healthy controls were included. Percentages and absolute numbers of NKT cells were measured with expression of the CTSL gene., Results: 124 subjects: with T1D (n = 48), siblings (n = 44) and controls (n = 32) were included. HbA1c was greater and C-peptide lower in T1D than the other groups and sibling age was higher (p < 0.001). There were no differences in NKT cells between T1D (0.176 ± 0.202) and controls (0.118 ± 0.133), but the percentage was higher in siblings (0.246 ± 0.188; p = 0.002). Lower level of expression of the CTSL gene associated with both absolute number (r: 0.4607; 95% CI: -0.08425 to -0.7935; p = 0.043) and percentage of NKT cells (r: 0.4540; 95% CI: -0.0927 to -0.7903; p = 0.045) in the T1D group., Conclusions: Patients with T1D have lower percentage and absolute number of NKT cells compared to their siblings. NKT cells absolute numbers are correlated with the expression of CTSL in T1D patients.
- Published
- 2016
17. Antidiabetic, antihyperlipidemic and anti-inflammatory effects of tilianin in streptozotocin-nicotinamide diabetic rats.
- Author
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García-Díaz JA, Navarrete-Vázquez G, García-Jiménez S, Hidalgo-Figueroa S, Almanza-Pérez JC, Alarcón-Aguilar FJ, Gómez-Zamudio J, Cruz M, Ibarra-Barajas M, and Estrada-Soto S
- Subjects
- 3T3-L1 Cells, Adipose Tissue drug effects, Adipose Tissue metabolism, Animals, Aorta drug effects, Aorta metabolism, Blood Glucose metabolism, Diabetes Mellitus, Experimental blood, Diabetes Mellitus, Experimental genetics, Fatty Acids metabolism, Gene Expression Profiling, Gene Expression Regulation drug effects, Lipogenesis drug effects, Lipogenesis genetics, Male, Metformin pharmacology, Metformin therapeutic use, Mice, Molecular Docking Simulation, Niacinamide, Oxidation-Reduction drug effects, Rats, Wistar, Streptozocin, Anti-Inflammatory Agents therapeutic use, Diabetes Mellitus, Experimental drug therapy, Flavonoids therapeutic use, Glycosides therapeutic use, Hypoglycemic Agents therapeutic use, Hypolipidemic Agents therapeutic use
- Abstract
Flavonoids from medicinal plants have been used in traditional medicine to treat a variety of prevalent diseases. Flavones activate the signaling pathways promoting fuel metabolism and insulin sensitizing in hepatocytes and adipocytes, which suggests that flavones may have the potential to exert in vivo antidiabetic and antihyperlipidemic effects. Thus, the aim of the current study was to determine the antidiabetic, antihyperlipidemic and anti-inflammatory effects of tilianin in diabetic rats. Also, to understand the mechanism involved using in vitro 3T3-L1 cells and tissues from experimental animals treated with test samples through molecular profile studies. Non insulin-dependent diabetic mellitus (NIDDM) rats were treated over a short period (for 10 days) with 60mg/Kg/day of tilianin. After treatment, a biochemical blood profile was determined. Also, adipose and thoracic aortic tissues were used to determine pro-inflammatory profile, adiponectin and adhesion molecules by real-time PCR. In 3T3-L1 cells pretreated with tilianin (10μM), PPARα, PPARγ, GLUT4, FATP-1 and ACSL-1 mRNA expression were measured. In order to explain the potential PPARα interaction with tilianin, a docking study with PPARα was carried out. Thus, intragastric administration of tilianin and metformin induced a decrease in plasma glucose (GLU) in diabetic rats on day 6, and remained significantly lower until the end of the treatment; also blood triacylglycerides (TAG) and cholesterol (CHOL) (p<0.05) were diminished. Moreover, IL-1β and IL-18 expression was significantly decreased in adipose tissue (p<0.05); meanwhile adiponectin was significantly overexpressed (p<0.05). Besides, ICAM-1 expression was significantly reduced in aortic tissue (p<0.05). In 3T3-L1 cells it was found that tilianin increased PPARα and ACSL1 mRNA levels (p<0.05). Finally, tilianin docking studies with PPARα showed polar interactions with Glu269, Tyr314, His 440 and Tyr464 residues. In conclusion, short-term tilianin treatment might exert its antidiabetic and antihyperlipidemic effect by modulating a pro-inflammatory profile, and increasing adiponectin expression. In addition, our results suggest the possible interaction of tilianin with PPARα., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)
- Published
- 2016
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18. Effect of bis-1,4-dihydropyridine in the kidney of diabetic rats.
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Gómez-Pliego R, Gómez-Zamudio J, Velasco-Bejarano B, Ibarra-Barajas M, and Villalobos-Molina R
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- Albuminuria drug therapy, Animals, Body Weight drug effects, In Vitro Techniques, Kidney drug effects, Male, Organ Size drug effects, Perfusion, Proteinuria drug therapy, Rats, Rats, Wistar, Streptozocin, Calcium Channel Blockers pharmacology, Calcium Channel Blockers therapeutic use, Diabetes Mellitus, Experimental complications, Diabetic Nephropathies etiology, Diabetic Nephropathies prevention & control, Dihydropyridines pharmacology, Dihydropyridines therapeutic use, Kidney blood supply, Vasodilation drug effects
- Abstract
The in vivo effectiveness of 4-dihydropyridine (bis-1,4-DHP), a new calcium-channel blocker, as a nephroprotector in isolated perfused kidney was evaluated by determining its effects on parameters associated with renal injury in diabetic rats. Diabetes in male Wistar rats, control, diabetic, control + bis-1,4-DHP, and diabetic + bis-1,4-DHP, was induced by a single administration of STZ (55 mg·kg(-1), i.p.). In the drug-treated groups, treatment with bis-1,4-DHP (10 mg·kg(-1)·day(-1)) started one week before diabetes induction; bis-1,4-DHP was dissolved in DMSO (0.3%) and suspended in drinking water with carboxymethyl cellulose (3%). Parameters evaluated were body weight, blood glucose, albuminuria, proteinuria, creatinine, urea excretion, kidney's weight / body weight ratio, and kidney perfusion pressure in all rat groups at different times of diabetes (2, 4, 6, and 10 weeks). Kidney weight of diabetic rats significantly increased vs. control, control + bis-1,4-DHP, and diabetic + bis-1,4-DHP rats at different times of diabetes. The ratios % kidney weight / 100 g body weight were different between control, control + bis-1,4-DHP, and diabetic + bis-1,4-DHP rats vs. diabetic rats (P < 0.05). Kidney perfusion pressure was decreased by diabetes, while it was partially recovered by bis-1,4-DHP treatment in response to phenylephrine. Bis-1,4-DHP had a tendency to decrease hyperglycemia vs. diabetic rats, even though glycemia was too high as compared with controls, and it ameliorated albuminuria, creatinine, and urea excretion, suggesting a favorable effect on renal haemodynamics. Bis-1,4-DHP, by inhibiting Ca(2+) entrance, induced vasodilation in renal vascular bed and thus may have a nephroprotective effect against diabetes-induced renal dysfunction, but does not have significant impact on hyperglycemia.
- Published
- 2013
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19. Selective agonists reveal alpha(1A)- and alpha(1B)-adrenoceptor subtypes in caudal artery of the young rat.
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Parés-Hipólito J, Gómez-Zamudio JH, Gallardo-Ortiz IA, López-Guerrero JJ, Santamaría-Ortiz J, Ibarra M, and Villalobos-Molina R
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- Adrenergic alpha-1 Receptor Antagonists, Adrenergic alpha-Antagonists pharmacology, Animals, Arteries physiology, Carbachol pharmacology, Dose-Response Relationship, Drug, Imidazoles pharmacology, In Vitro Techniques, Indoles pharmacology, Male, Phenylephrine pharmacology, Piperazines pharmacology, Prazosin pharmacology, Rats, Rats, Wistar, Receptors, Adrenergic, alpha-1 physiology, Tetrahydronaphthalenes pharmacology, Thymine pharmacology, Adrenergic alpha-1 Receptor Agonists, Adrenergic alpha-Agonists pharmacology, Arteries drug effects, Tail blood supply
- Abstract
Multiple alpha(1)-adrenoceptors were evaluated in caudal artery of the young Wistar rat using selective agonists and antagonists. Arteries were exposed to the selective alpha(1A)-adrenoceptor agonist, A-61603 (N-[5-(4,5-dihydro-1H-imidazol-2-yl)-2-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl] methanesulfonamide) or to phenylephrine and to prazosin (alpha(1)-adrenoceptor antagonist), or the selective alpha(1A)-adrenoceptor antagonists 5-methylurapidil, RS 100329 (5-methyl-3-[3-[4-[2-(2,2,2,-trifluoroethoxy)phenyl]-1-piperazinyl]propyl]-2,4-(1H)-pyrimidinedione), RS 17053 (N-[2(2-cyclopropylmethoxy) ethyl]-5-chloro-alpha, alpha-dimethyl-1H-indole-3-ethanamide), and the selective alpha(1D)-adrenoceptor antagonist BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5] decane-7,9-dione). Results showed a 100-fold higher potency of A-61603 for the alpha(1)-adrenoceptor present in the artery, compared with phenylephrine. Prazosin displaced both agonists with high affinity, whereas 5-methylurapidil, RS 100329 and RS 17053 displaced A-61603 with high affinity, indicating the presence of alpha(1A)-adrenoceptors. The selective alpha(1A)-adrenoceptor antagonists blocked phenylephrine responses with low affinity, suggesting that phenylephrine activated a second receptor population in caudal artery. BMY 7378 antagonized with low affinity both A-61603 and phenylephrine-induced contractions, indicating absence of alpha(1D)-adrenoceptors in the vessel. The results suggest that functional alpha(1B)-adrenoceptors are present in caudal arteries of the young Wistar rat.
- Published
- 2006
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20. Chloroethylclonidine reveals that alpha (1 A)-adrenoceptors mediate contraction in aorta of alpha (1 D)-adrenoceptor knockout mice.
- Author
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Lázaro-Suárez ML, Gómez-Zamudio JH, Gallardo-Ortíz IA, Tanoue A, Tsujimoto G, Farias-Rodríguez VM, and Villalobos-Molina R
- Subjects
- Adrenergic alpha-1 Receptor Antagonists, Animals, Aorta drug effects, Clonidine antagonists & inhibitors, Clonidine pharmacology, Dose-Response Relationship, Drug, Imines pharmacology, In Vitro Techniques, Mice, Mice, Knockout, Norepinephrine, Piperazines pharmacology, Piperidines pharmacology, Receptors, Adrenergic, alpha-1 genetics, Vasoconstriction drug effects, Vasoconstrictor Agents, Adrenergic alpha-Antagonists pharmacology, Aorta metabolism, Clonidine analogs & derivatives, Receptors, Adrenergic, alpha-1 physiology
- Abstract
1 We have characterized the alpha(1)-adrenoceptor subtypes present in isolated aorta of the alpha(1D)-adrenoceptor knockout (KO) mice, by chloroethylclonidine (CEC)-induced alkylation and their protection by selective alpha(1)-adrenoceptor antagonists. 2 The alpha(1D)-adrenoceptor is involved in the contractile response to noradrenaline in wild type (WT) mouse aorta. 3 In WT mice 5-methylurapidil (5-MU, an alpha(1A)-adrenoceptor antagonist) or BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl] ethyl]-8-azaspiro[4.5] decane-7,9 dione, a selective alpha(1D)-adrenoceptor antagonist), protected the receptors from CEC-induced (alpha(1B/D)-adrenoceptor) alkylation, the combination of both antagonists resulted in complete protection, while AH11110A (1-[biphenyl-2-yloxy]-4-imino-4-piperidin-1-yl-butan-2-ol, an alpha(1B)-adrenoceptor antagonist) did not protect. 4 In aorta of KO mice there was a 19-fold rightward shift in noradrenaline effective concentration (EC(50)) compared with WT; while 5-MU alone or in combination with AH11110A protected alpha(1)-adrenoceptors to the same extent. 5 The data indicate that alpha(1A)-adrenoceptors mediate contraction and suggest their role in maintaining homeostasis in the alpha(1D)-adrenoceptors KO mice.
- Published
- 2005
- Full Text
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21. Evidence for the use of agonists to characterize alpha 1-adrenoceptors in isolated arteries of the rat.
- Author
-
Gómez-Zamudio J, Lázaro-Suárez ML, Villalobos-Molina R, and Urquiza-Marín H
- Subjects
- Animals, Dose-Response Relationship, Drug, Endothelium, Vascular physiology, In Vitro Techniques, Male, Muscle Contraction drug effects, Rats, Adrenergic alpha-1 Receptor Agonists, Adrenergic alpha-Agonists pharmacology, Arteries drug effects, Muscle, Smooth, Vascular drug effects
- Published
- 2002
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