RESUMEN
Background/aim: Oxidative stress and advanced glycation end products (AGEs) formation are proposed as effective mechanisms in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD). 1,25(OH)2D3 was proposed to have antioxidant, antiinflammatory and antiglycation properties. In this study, the effect of 1,25(OH)2D3 treatment on oxidative stress parameters and AGEs levels together with hepatic histopathology was investigated in high fructose (HFr) or ethanol (EtOH)-treated rats. Materials and methods: Rats were treated with fructose (30%) or ethanol (5-20%) in drinking water with and without 1,25(OH)2D3 treatment (5 µg/kg two times a week) for 8 weeks. Insulin resistance (IR), oxidative stress parameters, AGEs, triglyceride (TG), and hydroxyproline (Hyp) levels together with histopathology were investigated in the liver. Results: 1,25(OH)2D3 decreased hepatic reactive oxygen species, lipid and protein oxidation products together with histopathological improvements in HFr- and EtOH-treated rats. 1,25(OH)2D3 treatment was observed to decrease significantly serum and hepatic AGEs in HFr group, and hepatic AGEs in EtOH group. Conclusion: Our results clearly show that 1,25(OH)2 D3 treatment may be useful in the alleviation of hepatic lesions by decreasing glycooxidant stress in both NAFLD and ALD models created by HFr- and EtOH-treated rats, respectively.
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Enfermedad del Hígado Graso no Alcohólico , Estrés Oxidativo , Animales , Calcitriol/metabolismo , Etanol , Fructosa/metabolismo , Productos Finales de Glicación Avanzada/metabolismo , Hígado/metabolismo , RatasRESUMEN
The endothelin (EDN) axis (EDN1 and EDN1 receptor A, EDNRA) is involved in cellular growth, differentiation, invasiveness, and tumor progression in several cancers. We wanted to examine the possible impact of single nucleotide polymorphisms (SNPs) of EDN1 and EDNRA genes on papillary thyroid cancer (PTC) development and general characteristics of PTC. Study population consist of 113 PTC patients and 185 controls. EDN1 (G5665T, T-1370G) and EDNRA (C TT70G, G-231A) SNPs were investigated by real-time PCR. The GG genotype of EDNRA + 70 SNP was associated with threefold increased PTC risk (p = 0.01), and the combined CG + GG genotype was 2.48 fold higher among PTC patients compared to controls. The variant EDNRA - 231 allele was overrepresented in PTC patients according to controls (p = 0.05). The combined GT + TT genotype of EDN1 5665 SNP was related with late (age after 40 years) PTC onset (p = 0.04), and was more prominent among male patients with PTC according to females (p = 0.03). No significant associations between PTC and - 1370 SNP were found. There were no relationships between laboratory parameters and investigated polymorphisms. The EDNRA + 70 SNP was associated with PTC development. The EDN1 5665 SNP was linked with increased risk for late PTC onset and was more prominent among male patients with PTC.
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Endotelina-1/genética , Receptor de Endotelina A/genética , Cáncer Papilar Tiroideo/genética , Adulto , Anciano , Alelos , Endotelina-1/fisiología , Endotelinas/genética , Femenino , Frecuencia de los Genes/genética , Predisposición Genética a la Enfermedad/genética , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Receptor de Endotelina A/fisiología , Receptores de Endotelina/genética , Factores de Riesgo , Neoplasias de la TiroidesRESUMEN
BACKGROUND: Methylglyoxal (MG) is a highly reactive dicarbonyl compound. It is produced by processes like glycolysis, glucose autooxidation, lipid peroxidation, and protein glycation. It is a major precursor of advanced glycation end products (AGE). It also exacerbates oxidative stress in the organism. Although there are some in vitro studies investigating the effect of resveratrol (RES) as an antioxidant and antiglycating agent on MG-induced toxicity, in vivo effect of RES is unknown. Therefore, we aimed to investigate the efficiency of RES in chronic MG-treated rats. METHODS: Rats were given incrementally increased doses (100-300â¯mg/kg) of MG in drinking water for ten weeks. RES (10â¯mg/kg ip) was administered together with MG. Reactive oxygen species (ROS) formation, thiobarbituric reactive substances (TBARS), protein carbonyl (PC), advanced oxidation protein products (AOPP) and AGE levels as well as ferric reducing antioxidant power (FRAP) values were determined in plasma and liver. RESULTS: Significant increases in plasma TBARS, PC, AOPP and AGE and fructosamine levels were detected in MG-treated rats. However, plasma ROS and FRAP levels remained unchanged. Hepatic ROS, TBARS, PC and AOPP, but not AGE and FRAP levels were also increased in MG-treated rats. RES treatment diminished high levels of plasma PC, AOPP and AGE levels in MG-treated rats. Additionally, significant decreases in hepatic ROS, TBARS, PC and AOPP levels together with histopatological amelioration were detected due to RES treatment in MG-treated rats. CONCLUSIONS: Our results indicate that RES may be considered as a protective agent against glycoxidative stress generated by in vivo MG treatment.
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Productos Finales de Glicación Avanzada/sangre , Productos Finales de Glicación Avanzada/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Oxidación-Reducción/efectos de los fármacos , Estilbenos/farmacología , Animales , Antioxidantes/metabolismo , Fructosamina/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Masculino , Estrés Oxidativo/efectos de los fármacos , Sustancias Protectoras/farmacología , Piruvaldehído/farmacología , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Resveratrol , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoRESUMEN
High levels of homocysteine (Hcy) have neurotoxic effects. Homocysteine thiolactone (HcyT), a thioester of Hcy, plays a role in Hcy-induced toxicity. In this study, effects of HcyT treatment (500â¯mg/kg body weight/day in drinking water) for 6 weeks on serum Hcy levels and brain prooxidant-antioxidant balance were investigated in rats. The effect of N-acetylcysteine (NAC) treatment (1â¯g/kg body weight/day in chow) for 6 weeks on HcyT-induced neurotoxicity was evaluated. Reactive oxygen species (ROS), thiobarbituric acid reactive substances (TBARS), diene conjugate (DC), protein carbonyl (PC) and advanced oxidation protein products (AOPP) were determined in the brain tissue. Ferric reducing antioxidant power (FRAP) and non-protein sulfydryl groups (NPSH) levels as well as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were also measured to evaluate the antioxidant potential of brain the tissue. HcyT elevated serum Hcy levels and brain ROS, TBARS, DC, PC and AOPP levels. However, HcyT did not affect FRAP levels and SOD, and GSH-Px activities. NAC treatment decreased serum Hcy and brain ROS, TBARS, DC, PC and AOPP levels in HCyT-treated rats. Our results indicate that NAC supplementation may be effective in decreasing serum Hcy levels and HcyT-induced oxidative stress in brain of rats.
RESUMEN
BACKGROUND: Oxidative stress and increased DNA damage have been implicated in the etiopathogenesis of vitiligo. Oxidative DNA damage is mainly repaired by the base excision repair (BER) pathway. AIM: We sought to determine whether polymorphisms in DNA repair genes may have a role in the pathogenesis of vitiligo. MATERIALS AND METHODS: We conducted a study including 100 patients with vitiligo and age- and sex-matched 193 control subjects to examine the role of single-nucleotide polymorphisms of BER genes, human 8-oxoG DNA N-glycosylase 1 (codon 326), apurinic/apyrimidinic endonuclease 1 (APE1) (codon 148), and X-ray repair cross-complementing group 1 (codon 399) as risk factors for vitiligo. These polymorphisms were determined by quantitative real-time polymerase chain reaction and melting curve analysis. RESULTS: No significant association was observed between the variant alleles of studied genes and vitiligo. CONCLUSION: However, we showed that the presence of APE1 148Glu variant allele is associated with leukotrichia. This preliminary study suggests that APE1 (codon 148) polymorphism may play a role in vitiligo pathogenesis.
RESUMEN
AIM: Increases in oxidative stress and advanced glycation end-products (AGE) formation play an important role in the pathogenesis of aging. Carnosine (CAR; ß-alanyl-L-histidine) has anti-oxidant and antiglycating properties. We investigated the effect of CAR supplementation on AGE levels, and protein and lipid oxidation products in the serum and liver tissue in aged rats. METHODS: Young (3 months-of-age) and aged (20 months-of-age) rats were injected with CAR (250 mg/kg/daily; i.p.; 5 days per week) for 2 months. At the end of this period, AGE, protein carbonyl, advanced oxidized protein products, and malondialdehyde levels were determined in the serum and liver tissue. Furthermore, reactive oxygen species formation and ferric reducing anti-oxidant power values were measured. RESULTS: AGE, malondialdehyde, protein carbonyl and advanced oxidized protein products levels, and reactive oxygen species formation were higher in the serum and liver tissue of aged rats compared with young rats. CAR treatment was observed to significantly decrease AGE, malondialdehyde, protein carbonyl and advanced oxidized protein products levels, and reactive oxygen species formation in the serum and liver of aged rats. CONCLUSIONS: These results clearly show that CAR might be useful for decreasing glycoxidant stress in aged rats. Geriatr Gerontol Int 2017; 17: 2610-2614.
Asunto(s)
Envejecimiento/efectos de los fármacos , Carnosina/uso terapéutico , Productos Finales de Glicación Avanzada/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Animales , Antioxidantes , Femenino , Hígado/efectos de los fármacos , Masculino , Oxidantes , Ratas , Ratas WistarRESUMEN
Methylglyoxal (MG) is generated from glycolytic metabolites, lipid peroxidation, glucose autooxidation and protein glycation. It is a prooxidant inducing oxidative stress and formation of advanced glycation end products (AGE). Effect of carnosine (CAR) as an antioxidant on toxicity due to MG has generated interest. In this study, rats were given incrementally increased doses (100-300 mg/kg) of MG in drinking water for ten weeks. CAR (250 mg/kg i.p.) was administered with MG. Plasma thiobarbituric reactive substances (TBARS), protein carbonyl (PC), advanced oxidation protein products (AOPP) and AGE levels were elevated by MG, and CAR decreased PC, AOPP and AGE levels. MG increased liver reactive oxygen species (ROS), TBARS, PC and AOPP levels, which were decreased by CAR. Thus, in vivo role of CAR on chronic MG administration was observed to suppress the generated hepatic and plasma oxidative stress.
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Productos Avanzados de Oxidación de Proteínas/antagonistas & inhibidores , Antioxidantes/farmacología , Carnosina/farmacología , Productos Finales de Glicación Avanzada/antagonistas & inhibidores , Hígado/efectos de los fármacos , Piruvaldehído/antagonistas & inhibidores , Productos Avanzados de Oxidación de Proteínas/agonistas , Productos Avanzados de Oxidación de Proteínas/metabolismo , Animales , Productos Finales de Glicación Avanzada/agonistas , Productos Finales de Glicación Avanzada/metabolismo , Inyecciones Intraperitoneales , Peroxidación de Lípido/efectos de los fármacos , Hígado/metabolismo , Masculino , Estrés Oxidativo/efectos de los fármacos , Carbonilación Proteica , Piruvaldehído/toxicidad , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/agonistas , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Especies Reactivas de Oxígeno/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoRESUMEN
The effect of N-acetylcysteine (NAC) (1 g/kg body weight/day) on serum homocysteine (Hcy) levels, insulin resistance (IR), and hepatic and renal prooxidant-antioxidant balance was evaluated in rats treated with homocysteine thiolactone (HcyT) (500 mg/kg body weight/day for 6 weeks). Reactive oxygen species (ROS), malondialdehyde (MDA), glutathione, ferric reducing antioxidant power, and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were determined in the liver and kidney. HcyT elevated serum Hcy levels and caused IR, but liver and kidney function tests remained unchanged. HcyT increased ROS and MDA without any change in hepatic antioxidants, but it elevated renal SOD and GSH-Px activities. NAC decreased serum Hcy, hepatic and renal ROS and MDA levels, and renal SOD and GSH-Px activities in rats with high Hcy levels. However, it did not ameliorate IR. Our results indicate that NAC supplementation may be effective in decreasing Hcy levels and Hcy-induced hepatic and renal oxidative stress.
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Acetilcisteína/farmacología , Suplementos Dietéticos , Homocisteína/análogos & derivados , Homocisteína/sangre , Riñón/patología , Hígado/patología , Estrés Oxidativo/efectos de los fármacos , Animales , Antioxidantes/metabolismo , Depuradores de Radicales Libres/farmacología , Glutatión/metabolismo , Homocisteína/farmacología , Riñón/efectos de los fármacos , Riñón/metabolismo , Pruebas de Función Renal , Peroxidación de Lípido/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Pruebas de Función Hepática , Masculino , Malondialdehído/metabolismo , Oxidantes/metabolismo , Oxidación-Reducción , Protectores contra Radiación/farmacología , Ratas , Ratas WistarRESUMEN
Steatosis, the first lesion in non-alcoholic fatty liver disease (NAFLD), may progress to fibrosis, cirrhosis, and hepatocellular carcinoma. Steatosis predisposes the liver to oxidative stress, inflammation, and cytokines. Betaine (BET) has antioxidant, antiinflammatory and hepatoprotective effects. However, the effects of BET on liver fibrosis development are unknown. Rats were treated with high-fat diet (60% of total calories from fat) for 14weeks. Carbon tetrachloride (0.2mL/kg; two times per week; i.p.) was administered to rats in the last 6weeks with/without commercial food containing BET (2%; w/w). Serum liver function tests and tumor necrosis factor-α, insulin resistance, hepatic triglyceride (TG) and hydroxyproline (HYP) levels and oxidative stress parameters were determined along with histopathologic observations. Alpha-smooth muscle-actin (α-SMA), transforming growth factor-ß1 (TGF-ß1) and type I collagen (COL1A1) protein expressions and mRNA expressions of matrix metalloproteinase-2 (MMP-2) and its inhibitors (TIMP-1 and TIMP-2) were evaluated. BET decreased TG and HYP levels, prooxidant status and fibrotic changes in the liver. α-SMA, COL1A1 and TGF-ß1 protein expressions, MMP-2, TIMP-1, and TIMP-2 mRNA expressions diminished due to BET treatment. BET has an antifibrotic effect and this effect may be related to its antioxidant and antiinflammatory actions together with suppression on HSC activation.
Asunto(s)
Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Betaína/uso terapéutico , Cirrosis Hepática/tratamiento farmacológico , Hígado/efectos de los fármacos , Actinas/metabolismo , Animales , Tetracloruro de Carbono/toxicidad , Colágeno Tipo I/metabolismo , Cadena alfa 1 del Colágeno Tipo I , Dieta Alta en Grasa , Femenino , Metabolismo de los Lípidos/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Cirrosis Hepática/inducido químicamente , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 2 de la Matriz/metabolismo , Ratas , Ratas Sprague-Dawley , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
BACKGROUND: This study was designed to compare the performances of HPLC (High Performance Liquid Chromatography) and LC-MS/MS (Liquid Chromatography-Tandem Mass Spectrometry) methods in 25 (OH) D3 testing. METHODS: This study is comprised of 306 randomly chosen plasma samples from the subjects who applied for routine measurement of 25 (OH) D3. Plasma 25 (OH) D3 levels were quantified using HPLC and LC-MS/MS. The LC-MS/MS method was used as the reference method. The linearity, precision, carry-over, limit of blank, limit of detection (LoD), and comparison studies were done for method validation. Accuracy was tested using external quality assurance samples. RESULTS: Coefficients of variation for both methods were at around 10.0%. The HPLC and LC-MS/MS assays were linear over the working range from 5.0 to 100 ng/mL (r > 0.99). The HPLC assay showed a higher LoD compared to LC-MS/MS (5.1 vs. 1.6 ng/mL, respectively). Results from external quality assurance samples were within ? 1 SD range for both methods. The comparison study revealed good correlation between HPLC and LC-MS/MS methods (y = 1.054x - 1.981 with a small mean bias (-0.953) (r = 0.9752)), when all samples were included, regardless of their 25 (OH) D3 levels. However, the correlation was poor for samples with 25 (OH) D3 concentrations lower than 10 ng/mL. CONCLUSIONS: Both methods have acceptable performance characteristics for use in clinical diagnostic applications. A good comparability was obtained between HPLC and LC-MS/MS methods. However, LoD of HPLC assay was higher and there was a poor correlation between the two systems for samples with 25 (OH) D3 concentrations below 10 ng/mL, showing that LC-MS/MS system is more successful in measuring samples with low 25 (OH) D3 concentration.
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Calcifediol/sangre , Cromatografía Líquida de Alta Presión , Espectrometría de Masas en Tándem , Adulto , Biomarcadores/sangre , Calibración , Cromatografía Líquida de Alta Presión/normas , Femenino , Humanos , Límite de Detección , Modelos Lineales , Masculino , Persona de Mediana Edad , Estándares de Referencia , Reproducibilidad de los Resultados , Espectrometría de Masas en Tándem/normasRESUMEN
The aim of this study was to investigate the effect of betaine (BET) on alcoholic liver fibrosis in rats. Fibrosis was experimentally generated with ethanol plus carbon tetrachloride (ETH+CCl4) treatment. Rats were treated with ETH (5% v/v in drinking water) for 14 weeks. CCl4 was administered intraperitoneally (i.p.) 0.2mL/kg twice a week to rats in the last 6 weeks with/without commercial food containing BET (2% w/w). Serum hepatic damage markers, tumor necrosis factor-α, hepatic triglyceride (TG) and hydroxyproline (HYP) levels, and oxidative stress parameters were measured together with histopathologic observations. In addition, α-smooth muscle-actin (α-SMA), transforming growth factor-ß1 (TGF-ß1) and type I collagen (COL1A1) protein expressions were assayed immunohistochemically to evaluate stellate cell (HSC) activation. mRNA expressions of matrix metalloproteinase-2 (MMP-2) and its inhibitors (TIMP-1 and TIMP-2) were also determined. BET treatment diminished TG and HYP levels; prooxidant status and fibrotic changes; α-SMA, COL1A1 and TGF-ß protein expressions; MMP-2, TIMP-1 and TIMP-2 mRNA expressions in the liver of fibrotic rats. In conclusion, these results indicate that the antifibrotic effect of BET may be related to its suppressive effects on oxidant and inflammatory processes together with HSC activation in alcoholic liver fibrosis.
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Betaína/uso terapéutico , Células Estrelladas Hepáticas/efectos de los fármacos , Cirrosis Hepática Alcohólica/prevención & control , Cirrosis Hepática Experimental/prevención & control , Hígado/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Animales , Antioxidantes/metabolismo , Betaína/administración & dosificación , Biomarcadores/sangre , Peso Corporal/efectos de los fármacos , Femenino , Células Estrelladas Hepáticas/inmunología , Células Estrelladas Hepáticas/metabolismo , Células Estrelladas Hepáticas/patología , Peroxidación de Lípido/efectos de los fármacos , Hígado/inmunología , Hígado/metabolismo , Hígado/patología , Cirrosis Hepática Alcohólica/inmunología , Cirrosis Hepática Alcohólica/metabolismo , Cirrosis Hepática Alcohólica/patología , Cirrosis Hepática Experimental/inmunología , Cirrosis Hepática Experimental/metabolismo , Cirrosis Hepática Experimental/patología , Pruebas de Función Hepática , Tamaño de los Órganos/efectos de los fármacos , Ratas Sprague-DawleyRESUMEN
The aim of this study was to investigate the effect of carnosine (CAR) alone and together with vitamin E (Vit E) on alcoholic steatohepatitis (ASH) in rats. ASH was induced by ethanol (3 times; 5 g/kg; 12 h intervals, via gavage), followed by a single dose of lipopolysaccharide (LPS; 10 mg/kg; i.p.). CAR (250 mg/kg; i.p.) and Vit E (200 mg D-α-tocopherol/kg; via gavage) were administered 30 min before and 90 min after the LPS injection. CAR treatment lowered high serum transaminase activities together with hepatic histopathologic improvements in rats with ASH. Reactive oxygen species formation, malondialdehyde levels, myeloperoxidase activities and transforming growth factor ß1 (TGF-ß1) and collagen 1α1 (COL1A1) expressions were observed to decrease. These improvements were more remarkable in CAR plus Vit E-treated rats. Our results indicate that CAR may be effective in suppressing proinflammatory, prooxidant, and profibrotic factors in the liver of rats with ASH.
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Antioxidantes/farmacología , Carnosina/farmacología , Etanol/toxicidad , Lipopolisacáridos/toxicidad , Estrés Oxidativo/efectos de los fármacos , alfa-Tocoferol/farmacología , Animales , Hígado , Masculino , Malondialdehído/metabolismo , RatasRESUMEN
Diethylnitrosamine (DEN)-induced liver cancer normally develops in stages that progress from cirrhosis and carcinoma. Increased oxidative stress is suggested to play a role in DEN-induced carcinogenicity. Blueberries (BB) contain high antioxidant capacity. We investigated the effect of BB supplementation on development of DEN-induced cirrhosis and neoplastic lesions in the liver. Rats were injected with DEN (200 mg/kg; i.p.) three times with an interval of 15 days at 4, 6, and 8 weeks and sacrificed 8 weeks after the last DEN injection. They were also fed on 8% BB (w/w) containing chow for 16 weeks. Hepatic damage markers in serum were determined together with hepatic histopathological examinations. Hydroxyproline (HYP), malondialdehyde (MDA), diene conjugate (DC), protein carbonyl (PC), and glutathione (GSH) levels, and CuZn-superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities, and their mRNA expressions were measured. Protein and mRNA expressions of glutathione transferase-pi (GST-pi) were evaluated as a marker of preneoplastic lesions. BB supplementation decreased hepatic damage markers in serum and hepatic MDA, DC, and PC levels, but SOD, CAT, and GSH-Px activities and their mRNA expressions remained unchanged in DEN-treated rats. BB attenuated cirrhotic changes and decreased hepatic HYP levels and GST-pi expressions. Our results indicate that BB is effective in decreasing development of DEN-induced hepatic cirrhosis and preneoplastic lesions by acting as an antioxidant (radical scavenger) itself without affecting activities and mRNA expressions of antioxidant enzymes.
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Arándanos Azules (Planta)/química , Dietilnitrosamina/farmacología , Cirrosis Hepática/tratamiento farmacológico , Hígado/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Lesiones Precancerosas/tratamiento farmacológico , Animales , Antioxidantes/metabolismo , Catalasa/metabolismo , Glutatión/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Hígado/metabolismo , Cirrosis Hepática/metabolismo , Masculino , Malondialdehído/metabolismo , Lesiones Precancerosas/metabolismo , Ratas , Ratas Wistar , Superóxido Dismutasa/metabolismoRESUMEN
D-galactose (GAL) has been used as an animal model for brain aging and antiaging studies. GAL stimulates oxidative stress in several tissues including brain. Carnosine (CAR; ß-alanil-L-histidine) and taurine (TAU; 2-aminoethanesulfonic acid) exhibit antioxidant properties. CAR and TAU have anti-aging and neuroprotective effects. We investigated the effect of CAR and TAU supplementations on oxidative stress and brain damage in GAL-treated rats. Rats received GAL (300 mg/kg; s.c.; 5 days per week) alone or together with CAR (250 mg/kg/daily; i.p.; 5 days per week) or TAU (2.5% w/w; in rat chow) for 2 months. Brain malondialdehyde (MDA), protein carbonyl (PC) and glutathione (GSH) levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione transferase (GST) and acetylcholinesterase (AChE) activities were determined. Expressions of B cell lymphoma-2 (Bcl-2), Bax and caspase-3 were also evaluated in the brains by immunohistochemistry. GAL treatment increased brain MDA and PC levels and AChE activities. It decreased significantly brain GSH levels, SOD and GSH-Px but not GST activities. GAL treatment caused histopathological changes and increased apoptosis. CAR and TAU significantly reduced brain AChE activities, MDA and PC levels and elevated GSH levels in GAL-treated rats. CAR, but not TAU, significantly increased low activities of SOD and GSH-Px. Both CAR and TAU diminished apoptosis and ameliorated histopathological findings in the brain of GAL-treated rats. Our results indicate that CAR and TAU may be effective to prevent the development of oxidative stress, apoptosis and histopathological deterioration in the brain of GAL-treated rats.
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Antioxidantes/farmacología , Carnosina/farmacología , Galactosa/metabolismo , Estrés Oxidativo/efectos de los fármacos , Taurina/farmacología , Envejecimiento , Animales , Apoptosis/efectos de los fármacos , Glutatión Peroxidasa/metabolismo , Histidina/metabolismo , Masculino , Malondialdehído/metabolismo , Ratas Wistar , Superóxido Dismutasa/metabolismo , Taurina/metabolismoRESUMEN
D-galactose (GAL) causes aging-related changes and oxidative stress in the organism. We investigated the effect of whole fresh blueberry (BB) (Vaccinium corymbosum L.) treatment on oxidative stress in age-related brain damage model. Rats received GAL (300 mg/kg; s.c.; 5 days per week) alone or together with 5 % (BB1) and 10 % (BB2) BB containing chow for two months. Malondialdehyde (MDA),protein carbonyl (PC) and glutathione (GSH) levels, and Cu Zn-superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione transferase (GST) activities as well as acetylcholinesterase (AChE) activities were determined. Expressions of B cell lymphoma-2 (Bcl-2), Bax and caspase-3 were also evaluated in the brain by immunohistochemistry. MDA and PC levels and AChE activity increased, but GSH levels, SOD and GSH-Px activities decreased together with histopathological structural damage in the brain of GAL-treated rats. BB treatments, especially BB2 reduced MDA and PC levels and AChE activity and elevated GSH levels and GSH-Px activity. BB1 and BB2 treatments diminished apoptosis and ameliorated histopathological findings in the brain of GAL-treated rats. These results indicate that BB partially prevented the shift towards an imbalanced prooxidative status and apoptosis together with histopathological amelioration by acting as an antioxidant (radical scavenger) itself in GAL-treated rats.
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Arándanos Azules (Planta) , Lesiones Encefálicas/metabolismo , Lesiones Encefálicas/prevención & control , Galactosa/toxicidad , Estrés Oxidativo/fisiología , Extractos Vegetales/uso terapéutico , Animales , Antioxidantes/aislamiento & purificación , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Lesiones Encefálicas/patología , Galactosa/antagonistas & inhibidores , Masculino , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Ratas , Ratas Wistar , Resultado del TratamientoRESUMEN
High fat diet (HFD) is associated with oxidative stress induced fatty liver. Curcumin, an extract of Curcuma longa, has been shown to possess potent antioxidant and hypolipidemic properties. In this study, we investigated the effect of curcumin treatment on hepatic heme oxygenase-1 (HO-1) expression along with pro-oxidant-antioxidant status and lipid accumulation in rats fed an HFD. Male Sprague-Dawley rats were distributed among 4 groups: Group 1, which was fed the control diet (10% of total calories from fat); Group 2, which was fed the HFD (60% of total calories from fat); and groups 3 and 4, which received the HFD supplemented with curcumin and the control diet supplemented with curcumin (1 g/kg diet; w/w), respectively, for 16 weeks. HFD caused increases in hepatic lipid levels, production of reactive oxygen species, and lipid peroxidation. Further, HO-1 expression was significantly decreased. Histopathological examination showed hepatic fat accumulation and slight fibrotic changes. Curcumin treatment reduced hepatic lipids and oxidative stress parameters, and HO-1 expression was significantly increased. These findings suggest that increased HO-1 expression, along with suppressed oxidative stress as well as reduced hepatic fat accumulation and fibrotic changes, contribute to the beneficial effects of curcumin in attenuating the pathogenesis of fatty liver induced metabolic diseases.
Asunto(s)
Antioxidantes/farmacología , Curcumina/farmacología , Dieta Alta en Grasa , Hemo-Oxigenasa 1/metabolismo , Hígado/efectos de los fármacos , Animales , Curcuma , Hígado Graso/metabolismo , Hígado Graso/patología , Expresión Génica , Metabolismo de los Lípidos/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Cirrosis Hepática/metabolismo , Cirrosis Hepática/patología , Masculino , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismoRESUMEN
PURPOSE: Endothelin1 (EDN1) is well established marker of inflammation. The functions of EDN1 are mediated mainly by endothelin receptors type A (EDNRA). The etiopathogenesis of Hashimoto's thyroiditis (HT) remains still elusive although the role of chronic inflammation and subsequent endothelial dysfunction has been established. This study examined firstly the possible association of EDN1 (G5665Tand T-1370G) and EDNRA (C+70G and G-231A) single nucleotide polymorphisms (SNPs) with the occurrence of HT, and evaluates the relationship between genotypes and clinical/laboratory manifestation of HT. MATERIALS AND METHODS: We analyzed genotype and allele distributions of above mentioned polymorphisms in 163 patients with HT and 181 healthy controls by real-time PCR combined with melting curve analysis. RESULTS: No significant associations between HT and variant alleles of EDN1 5665 and -1370, as well as EDNRA +70 and -231 SNPs were found. Haplotype analysis demonstrated that there was a strong (D'=0.76, r(2)=0.487) and weak (D'=0.403, r(2)=0.086) linkage disequilibrium (LD) between EDN1 -1370 and 5665, and between EDNRA -231 and +70 SNPs, respectively. However, haplotype frequencies in patients were similar to those in controls. In addition, it was observed that the EDNRA +70 G allele had protective effect against early (at age before 40 years) disease onset of HT (OR: 0.51, 95% CI=0.32-0.79, p=0.003). CONCLUSION: Although no significant associations between susceptibility to HT with EDN1 5665 and -1370, as well as with EDNRA+70 and -231 SNPs were found, EDNRA +70 polymorphism was related with decreased risk for early onset HT.
Asunto(s)
Endotelina-1/genética , Enfermedad de Hashimoto/epidemiología , Enfermedad de Hashimoto/genética , Receptor de Endotelina A/genética , Adulto , Edad de Inicio , Análisis Mutacional de ADN , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Desequilibrio de Ligamiento , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Riesgo , TurquíaRESUMEN
AIM: d-galactose (GAL) causes aging-related changes and oxidative stress in the organism. We investigated the effect of whole fresh blueberry (BB; Vaccinium corymbosum L.) treatment on oxidative stress in age-related liver injury model. METHODS: Rats received GAL (300 mg/kg, s.c.; 5 days per week) alone or together with 5% (BB1) and 10% (BB2) BB-containing chow for 2 months. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, and hepatic malondialdehyde (MDA), protein carbonyl (PC) and glutathione (GSH) levels, and CuZn-superoxide dismutase (SOD1), glutathione peroxidase (GPx1) and glutathione transferase (GST) activities together with mRNA expressions of SOD1, GPx1, MnSOD (SOD2) and phospholipid hydroperoxide glutathione peroxidase (GPx4) were determined in GAL-treated rats. RESULTS: MDA and PC levels increased, but GSH levels, SOD1 and GPx1 activities decreased together with histopathological structural damage in the liver in GAL-treated rats. There was no change in hepatic mRNA expressions of SOD2 and GPx1, but SOD1 and GPx4 expressions decreased. BB1 and BB2 caused significant decreases in serum ALT and AST activities together with the amelioration in histopathological findings in GAL-treated rats. Both BB1 and BB2 reduced MDA and PC levels, and elevated GSH levels, and SOD1 and GPx1 activities. However, hepatic mRNA expressions of SOD1, SOD2, GPx1 and GPx4 remained unchanged in GAL-treated rats. CONCLUSIONS: These results show that BB restored liver pro-oxidant status together with histopathological amelioration by acting as an anti-oxidant (radical scavenger) itself without affecting mRNA expressions of anti-oxidant enzymes in GAL-treated rats.
Asunto(s)
Arándanos Azules (Planta) , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Galactosa/efectos adversos , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Animales , Hígado/efectos de los fármacos , Hígado/enzimología , Masculino , Ratas , Ratas WistarRESUMEN
PURPOSE: Endothelin 1 (EDN1) is a strong angiogenic and mitogenic factor, playing a key role in hypervascularization, thyroid follicle cell hyperplasia, and lymphocyte infiltration in the thyroid gland of patients with Graves' disease (GD). EDN1 induces angiogenesis and mitogenesis via endothelin receptor type A (EDNRA). This study examined the possible association of EDN1 (G5665T and T-1370G) and EDNRA (C+70G and G-231A) single nucleotide polymorphisms (SNPs) with the occurrence of GD, and evaluates the relationship between genotypes and clinical/laboratory manifestations of GD. MATERIALS AND METHODS: We analyzed genotype and allele distributions of EDN1 and EDNRA polymorphisms in 165 patients with GD and 181 healthy controls by real-time PCR combined with melting curve analysis. RESULTS: No significant associations between GD and variant alleles of the studied polymorphisms were observed. However, the anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-TG) levels in EDN1 G5665T GG genotype were higher than those in T allele carriers (GT+TT) (p=0.001 and p=0.026, respectively). In addition, anti-TPO levels in EDN1 T-1370G wild-type homozygous patients were found to be higher than in mutant gene carrying patients (GT+GG) (p=0.006). The presence of EDNRA+70G allele was associated with 3.37-fold increased risk for development of ophthalmopathy in GD patients (p=0.009). CONCLUSION: Although there were no associations between EDN1 (G5665T and T-1370G) and EDNRA (C+70G and G-231A) SNPs and susceptibility to GD, EDN1 G5665T and T-1370G polymorphisms were related to alterations of autoantibody production and EDNRA C+70G polymorphism is related with increased risk for ophthalmopathy in GD patients.
Asunto(s)
Enfermedad de Graves/genética , Oftalmopatía de Graves/genética , Receptor de Endotelina A/metabolismo , Adolescente , Adulto , Anciano , Formación de Anticuerpos/genética , Autoanticuerpos/sangre , Análisis Mutacional de ADN , Endotelina-1/metabolismo , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Enfermedad de Graves/complicaciones , Oftalmopatía de Graves/etiología , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Receptor de Endotelina A/genética , Adulto JovenRESUMEN
D-galactose (GAL) causes aging-related changes and oxidative stress in the organism. We investigated the effect of carnosine (CAR) or taurine (TAU), having antioxidant effects, on hepatic injury and oxidative stress in GAL-treated rats. Rats received GAL (300 mg/kg; s.c.; 5 days/week) alone or together with CAR (250 mg/kg/daily; i.p.; 5 days/week) or TAU (2.5 % w/w; in rat chow) for 2 months. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and hepatic malondialdehyde (MDA), protein carbonyl (PC) and glutathione (GSH) levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-0050x), and glutathione transferase (GST) activities were determined. Hepatic expressions of B cell lymphoma-2 (Bcl-2), Bax and Ki-67 were evaluated. Serum ALT, AST, hepatic MDA, and PC levels were observed to increase in GAL-treated rats. Hepatic Bax expression, but not Bcl-2, increased, Ki-67 expression decreased. GAL treatment caused decreases in GSH levels, SOD and GSH-Px activities in the liver. Hepatic mRNA expressions of SOD, but not GSH-Px, also diminished. CAR or TAU treatments caused significant decreases in serum ALT and AST activities. These treatments decreased apoptosis and increased proliferation and ameliorated histopathological findings in the livers of GAL-treated rats. Both CAR and TAU reduced MDA and PC levels and elevated GSH levels, SOD and GSH-Px (non significant in TAU + GAL group) activities. These treatments did not alter hepatic mRNA expressions of SOD and GSH-Px enzymes. Our results indicate that CAR and TAU restored liver prooxidant status together with histopathological amelioration in GAL-induced liver damage.