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1.
Acta Histochem ; 119(7): 719-726, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28923316

RESUMEN

Obesity is related to increased TNF-alpha production in different tissues. TNF-alpha is connected to mitochondrial dysfunction in the liver and also development of fatty infiltration of the liver. Also, postnatal change from normal to high-fat diet causes a significant increase in TNF-alpha serum levels. The aim of this research was to determine how maternal diet and switching male offspring to a different dietary regime after lactation influences rat liver. Ten female Sprague Dawley rats at nine weeks of age were randomly divided in two groups and fed either standard laboratory chow or high-fat diet during six weeks, and then mated with the same male subject. After birth and lactation male offspring from both groups were further divided into four subgroups depending on their subsequent diet. At 22 weeks of age, the animals were weighted, sacrificed and major organs were collected and weighted. Immunohistochemistry for TNF-alpha was performed on liver, and liver samples were analyzed for pathohistological changes. The group in which mothers were fed standard chow and offspring high-fat diet had the most pronounced changes: heaviest liver, poorest histopathological findings and strongest TNF-alpha immunohistochemical staining of liver parenchyma. High-fat diet during pregnancy and lactation and switching to high-fat diet postnatally affects liver weight, histological structure and TNF-alpha expression in male offspring.


Asunto(s)
Dieta , Regulación de la Expresión Génica/fisiología , Hígado/patología , Fenómenos Fisiológicos de la Nutrición , Tejido Parenquimatoso/patología , Factor de Necrosis Tumoral alfa/genética , Animales , Femenino , Inmunohistoquímica , Hígado/metabolismo , Masculino , Tamaño de los Órganos/fisiología , Periodo Posparto , Embarazo , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/metabolismo
2.
Acta Histochem ; 118(7): 711-721, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27577321

RESUMEN

In obesity, bone marrow adiposity increases and proinflammatory cytokines excretion activates RANK/RANKL/OPG system, which leads to increased bone resorption. The aim of this study was to analyze trabecular and cortical bone parameters in animals exposed to the high-fat diet in utero and after lactation. Skeletal organ of interest was the fifth lumbar vertebra, which is not exposed to biomechanical loading in rats. Further aims were to determine TNF-α and IL-6 serum concentrations, and the intensity of the TNF-α immunohistochemical staining in the bone marrow. Ten female Sprague Dawley rats, nine weeks old, were randomly divided in two groups and fed either standard laboratory chow or food rich in saturated fatty acids during five weeks, and then mated with genetically similar male subjects. After birth and lactation male offsprings from both groups were divided in four subgroups depending on the diet they were fed until twenty-two weeks of age. The highest cholesterol and triglyceride concentration were found in both groups of offsprings fed with high-fat diet. The lowest trabecular bone volume, lowest trabecular number and highest trabecular separation were found in offsprings fed with high-fat diet of mothers on standard laboratory chow. The same group of offsprings was also characterized by the highest intensity of TNF-α immunostaining in the bone marrow and the highest TNF-α serum concentration, which suggest that this proinflammatory cytokine has interfered with bone metabolism, possibly by stimulation of bone resorption, which led to inadequate trabecular bone development and bone modeling of the fifth lumbar vertebra.


Asunto(s)
Peso Corporal/fisiología , Resorción Ósea/metabolismo , Huesos/metabolismo , Dieta Alta en Grasa , Vértebras Lumbares/metabolismo , Obesidad/metabolismo , Animales , Femenino , Interleucina-6/metabolismo , Vértebras Lumbares/crecimiento & desarrollo , Masculino , Ligando RANK/metabolismo , Ratas Sprague-Dawley , Triglicéridos/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
3.
BMC Complement Altern Med ; 15: 233, 2015 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-26174335

RESUMEN

BACKGROUND: Micromeria croatica (Pers.) Schott is an aromatic plant from Lamiaceae family previously found to possess potent in vitro antioxidant activity which is mainly attributed to the high level of polyphenolic substances. The aim of this study was to investigate the hepatoprotective activity and possible underlying mechanisms of Micromeria croatica ethanolic extract (MC) using a model of carbon tetrachloride (CCl4)-induced liver injury in mice. METHODS: Male BALB/cN mice were randomly divided into seven groups: control group received saline, MC group received ethanolic extract of M. croatica in 5% DMSO (100 mg/kg b.w., p.o.), and CCl4 group was administered CCl4 dissolved in corn oil (2 mL/kg, 10% v/v, ip). MC50, MC200 and MC400 groups were treated with MC orally at doses of 50, 200 and 400 mg/kg once daily for 2 consecutive days, respectively, 6 h after CCl4 intoxication. The reference group received silymarin at dose of 400 mg/kg. At the end of experiment, blood and liver samples were collected for biochemical, histopathological, immunohistochemical and Western blot analyses. In addition, major phenolic compounds in MC were quantified by HPLC-DAD. RESULTS: CCl4 intoxication resulted in liver cells damage and oxidative stress and triggered inflammatory response in mice livers. MC treatment decreased ALT activity and prevented liver necrosis. Improved hepatic antioxidant status was evident by increased Cu/Zn SOD activity and decreased 4-hydroxynonenal (4-HNE) formation in the livers. Concomitantly, nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were overexpressed. The hepatoprotective activity of MC was accompanied by the increase in nuclear factor-kappaB (NF-κB) activation and tumor necrosis factor-alpha (TNF-α) expression, indicating amelioration of hepatic inflammation. Additionally, MC prevented tumor growth factor-ß1 (TGF-ß1) and α-smooth muscle actin (α-SMA) expression, suggesting the potential for suppression of hepatic fibrogenesis. CONCLUSION: These results of the present study demonstrated that MC possesses in vivo antioxidant and anti-inflammatory activity and exhibits antifibrotic potential, which are comparable to those of standard hepatoprotective compound silymarin.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas , Lamiaceae/química , Extractos Vegetales/farmacología , Sustancias Protectoras/farmacología , Animales , Tetracloruro de Carbono/toxicidad , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Ratones , Ratones Endogámicos BALB C
4.
Chem Biol Interact ; 230: 21-9, 2015 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-25656916

RESUMEN

Myricetin-3-O-α-rhamnoside (myricitrin) is a naturally occurring phenolic compound which possesses antioxidant and anti-inflammatory activity. The aim of this study was to determine the hepatoprotective effects of myricitrin. Myricitrin at doses of 10, 30 and 100 mg/kg and silymarin at dose of 100mg/kg were administered to BALB/cN mice by oral gavage, once daily for two consecutive days following carbon tetrachloride (CCl4)-intoxication. Myricitrin significantly ameliorated CCl4-induced increase in serum aspartate transaminase (AST) and alanine transaminase (ALT) levels and histopathological changes in the liver. Hepatic oxidative stress was reduced by myricitrin, as evidenced by the decrease in lipid peroxidation, with concomitant increase in glutathione (GSH) level and cytochrome P450 2E1 (CYP2E1) expression. In addition, cyclooxygenase-2 (COX-2) and tumor necrosis factor-alpha (TNF-α) overexpression in the liver was reduced, suggesting the suppression of inflammation. The expression of transforming growth factor-beta1 (TGF-ß1) and alpha-smooth muscle actin (α-SMA) was markedly ameliorated, indicating the inhibition of profibrotic response. Myricitrin also improved the regeneration of hepatic tissue after CCl4-intoxication, as evidenced by increased proliferating cell nuclear antigen (PCNA) expression. The results of the current study suggest that myricitrin exhibits a significant hepatoprotective activity. Myricitrin provided better hepatoprotection when compared to silymarin, which is consistent with its higher in vitro antioxidant potential.


Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Antioxidantes/farmacología , Intoxicación por Tetracloruro de Carbono/prevención & control , Flavonoides/farmacología , Alanina Transaminasa/sangre , Animales , Aspartato Aminotransferasas/sangre , Peso Corporal/efectos de los fármacos , Intoxicación por Tetracloruro de Carbono/tratamiento farmacológico , Intoxicación por Tetracloruro de Carbono/metabolismo , Proliferación Celular/efectos de los fármacos , Hepatocitos/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/prevención & control , Masculino , Ratones Endogámicos BALB C , Estrés Oxidativo/efectos de los fármacos , Silimarina/farmacología , Factor de Necrosis Tumoral alfa/metabolismo
5.
Toxicology ; 324: 98-107, 2014 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-25043994

RESUMEN

The aim of this study was to investigate the renoprotective activity of chlorogenic acid (CA) in a murine model of cisplatin (CP)-induced kidney injury. Male BALB/cN mice were gavaged daily with CA at 3, 10 and 30mg/kg for two successive days, 48h after intraperitoneal injection of CP (13mg/kg). On the fifth day, serum creatinine and blood urea nitrogen (BUN) levels were significantly increased in CP-intoxicated mice, which was recovered by CA. Renal oxidative stress, evidenced by increased 4-hydroxynonenal (4-HNE) expression, was significantly reduced with CA. Simultaneously, the overexpression of heme oxygenase 1 (HO-1) and cytochrome P450 E1 (CYP2E1) was attenuated. The inhibition of inflammatory response by CA was achieved through the reduction of tumor necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2) expression. Additionally, CA significantly suppressed p53, Bax active caspase-3, cyclin D1 and microtubule-associated protein 1 light chain 3 isoform B (LC3B) expression, suggesting the inhibition of both apoptosis and autophagy. The expression of multidrug resistance-associated proteins (Mrp1 and Mrp2) increased and organic cation transporter 2 (Oct2) decreased by CP, protecting the kidneys from nephrotoxicity by reducing the burden of tubular cells. CA dose-dependently restored Mrp1, Mrp2 and Oct2 expression. The recovery of kidney tissue form CP injury was accompanied by increased proliferating nuclear cell antigen (PCNA) expression. The results of this study suggest that CA attenuates CP-induced kidney injury through suppression of oxidative stress, inflammation, apoptosis and autophagy, with the improvement in kidney regeneration.


Asunto(s)
Lesión Renal Aguda/prevención & control , Ácido Clorogénico/farmacología , Cisplatino , Riñón/efectos de los fármacos , Sustancias Protectoras/farmacología , Lesión Renal Aguda/sangre , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/patología , Aldehídos/metabolismo , Animales , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Biomarcadores/sangre , Nitrógeno de la Urea Sanguínea , Caspasa 3/metabolismo , Ciclina D1/metabolismo , Ciclooxigenasa 2/metabolismo , Citocromo P-450 CYP2E1/metabolismo , Citoprotección , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Hemo-Oxigenasa 1/metabolismo , Mediadores de Inflamación/metabolismo , Riñón/metabolismo , Riñón/patología , Masculino , Proteínas de la Membrana/metabolismo , Ratones , Ratones Endogámicos BALB C , Proteínas Asociadas a Microtúbulos/metabolismo , Proteína 2 Asociada a Resistencia a Múltiples Medicamentos , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Proteínas de Transporte de Catión Orgánico/sangre , Transportador 2 de Cátion Orgánico , Estrés Oxidativo/efectos de los fármacos , Antígeno Nuclear de Célula en Proliferación/metabolismo , Regeneración/efectos de los fármacos , Factores de Tiempo , Factor de Necrosis Tumoral alfa/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Proteína X Asociada a bcl-2/metabolismo
6.
Coll Antropol ; 38(1): 179-87, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24851615

RESUMEN

Postpartum weight retention is a risk factor for the development of midlife obesity. Since dietary intake and breastfeeding practice could be promoters of weight loss during postpartum, the objective of this study was to investigate their influence on weight retention during six months postpartum. The study sample consisted of 83 lactating and 76 non-lactating Croatian women who were examined at three measurement waves: at 1 month +/- 1 week, 3 months +/- 1 week and 6 months +/- 1 week postpartum. At each measurement wave, two consecutive 24-hour dietary recalls were collected, and body weight measurements were made. Both groups had a daily energy intake lower by about 25% than recommended. Although both groups continuously decreased energy and macronutrient intake, lactating women had energy intake higher by 205 kcal (p = 0.048) and 370 kcal (p < 0.001) after one and three months, respectively. At six months postpartum lactating women had a higher intake of fat (p = 0.036) but a lower intake of protein (p = 0.009) compared with non-lactating mothers. After six months, lactating women retained 101.9% of pre-pregnancy weight, which was significantly less than the percentage of weight retained among non-lactating women (p = 0.014). Multiple regression analysis showed that weight retention were predicted by: type of feeding (beta = -0.281; p <0.001), and time since parturition (beta = -0.151; p < 0.001), while gestational weight gain (P = 0.491; p < 0.001), energy intake (b = 0.157; p < 0.001) and energy derived from fat (beta = 0.122; p = 0.035) were positive predictors. We concluded that the dietary intake of Croatian women and breastfeeding practice over six months significantly influence their weight loss.


Asunto(s)
Peso Corporal , Ingestión de Alimentos , Lactancia , Obesidad/epidemiología , Periodo Posparto , Adulto , Croacia , Femenino , Humanos , Obesidad/etiología , Estudios Prospectivos , Factores de Riesgo , Aumento de Peso
7.
Food Chem Toxicol ; 62: 397-406, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24025684

RESUMEN

The aim of this study was to investigate the therapeutic activity of isoquinoline alkaloid berberine against cisplatin (CP)-induced nephrotoxicity in mice. Berberine was administered at daily doses of 1, 2 and 3 mg/kg by gavage for two successive days, 48 h after intraperitoneal CP injection (13 mg/kg). Mice were sacrificed 24 h after the last dose of berberine. Histopathological changes and the increase in serum creatinine and blood urea nitrogen (BUN) induced by CP were significantly ameliorated by berberine in a dose-dependent manner. Additionally, oxidative/nitrosative stress, evidenced by the increase in renal 4-hydroxynonenal (4-HNE), 3-nitrotyrosine (3-NT), cytochrome P450 E1 (CYP2E1) and heme oxygenase (HO-1) expression, was significantly reduced. The expression of nuclear factor-kappaB (NF-κB), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) was markedly suppressed by berberine, indicating the inhibition of inflammatory response. Treatment of CP-intoxicated animals with berberine also significantly reduced the expression of p53, active caspase-3 as well as autophagy marker light chain 3B (LC3B) in the kidneys. The results of the current study showed the nephroprotective activity of berberine against CP-induced renal injury, which could be attributed to the inhibition of oxidative/nitrosative stress, inflammation, autophagy and apoptosis.


Asunto(s)
Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Berberina/farmacología , Cisplatino/efectos adversos , Riñón/efectos de los fármacos , Riñón/patología , Nefritis/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Sustancias Protectoras/farmacología , Aldehídos/metabolismo , Animales , Nitrógeno de la Urea Sanguínea , Creatinina/sangre , Citocromo P-450 CYP2E1/metabolismo , Riñón/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Nefritis/metabolismo , Tirosina/análogos & derivados , Tirosina/metabolismo
8.
Toxicology ; 310: 115-23, 2013 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-23770416

RESUMEN

The aim of this study was to investigate the effects of flavone luteolin against cisplatin (CP)-induced kidney injury in mice. Luteolin at doses of 10mg/kg was administered intraperitoneally (ip) once daily for 3 days following single CP (10 or 20mg/kg) ip injection. Mice were sacrificed 24h after the last dose of luteolin. The CP treatment significantly increased serum creatinine and blood urea nitrogen and induced pathohistological changes in the kidneys. Renal oxidative/nitrosative stress was evidenced by decreased glutathione (GSH) levels and increased 3-nitrotyrosine (3-NT) and 4-hydroxynonenal (4-HNE) formation as well as cytochrome P450 2E1 (CYP2E1) expression. The CP administration triggered inflammatory response in mice kidneys through activation of nuclear factor-kappaB (NF-κB) and overexpression of tumor necrosis factor-alpha (TNF-α) and cyclooxygenase-2 (COX-2). Simultaneously, the increase in renal p53 and caspase-3 expression indicated apoptosis of tubular cells. The administration of luteolin significantly reduced histological and biochemical changes induced by CP, decreased platinum (Pt) levels and suppressed oxidative/nitrosative stress, inflammation and apoptosis in the kidneys. These results suggest that luteolin is an effective nephroprotective agent, with potential to reduce Pt accumulation in the kidneys and ameliorate CP-induced nephrotoxicity.


Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Antineoplásicos/toxicidad , Apoptosis/efectos de los fármacos , Cisplatino/toxicidad , Enfermedades Renales/prevención & control , Platino (Metal)/metabolismo , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/farmacología , Antineoplásicos/farmacocinética , Biomarcadores/sangre , Western Blotting , Cisplatino/farmacocinética , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Inmunohistoquímica , Riñón/efectos de los fármacos , Riñón/inmunología , Riñón/metabolismo , Riñón/patología , Enfermedades Renales/inducido químicamente , Enfermedades Renales/metabolismo , Enfermedades Renales/patología , Pruebas de Función Renal , Luteolina/administración & dosificación , Luteolina/farmacología , Luteolina/uso terapéutico , Masculino , Ratones , Ratones Endogámicos BALB C , Estrés Oxidativo/efectos de los fármacos
9.
Food Chem Toxicol ; 51: 370-8, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23116643

RESUMEN

The aim of this study was to investigate the therapeutic potential of rosmarinic acid (RA), a natural phenolic, in the treatment of acute liver toxicity. RA at 10, 25 and 50mg/kg was administered by gavage once daily for 2 consecutive days, 6h after CCl(4) intoxication. CCl(4) intoxication caused hepatic necrosis and increased serum ALT activity. In the livers, oxidative/nitrosative stress was evidenced by increased 3-nitrotyrosine (3-NT) and thiobarbituric acid reactive substances (TBARS) formation and a significant decrease in Cu/Zn superoxide dismutase (SOD) activity. CCl(4) administration triggered inflammatory response in mice livers by activating nuclear factor-kappaB (NF-κB), which coincided with the induction of tumor necrosis factor-alpha (TNF-α) and cyclooxygenase-2 (COX-2). RA improved histological and serum markers of liver damage and significantly ameliorated oxidative/nitrosative stress and inflammatory response in liver tissue. Additionally, RA prevented transforming growth factor-beta1 (TGF-ß1) and alpha-smooth muscle actin (α-SMA) expression, suggesting suppression of profibrotic response. Furthermore, RA significantly inhibited the CCl(4)-induced apoptosis, which was evident from decreased cleavage of caspase-3. The hepatoprotective activity of RA coincided with enhanced NF-E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression. The results of this study indicates that RA possesses antioxidant, anti-inflammatory, antiapoptotic and antifibrotic activity against acute liver toxicity.


Asunto(s)
Intoxicación por Tetracloruro de Carbono/tratamiento farmacológico , Tetracloruro de Carbono/toxicidad , Cinamatos/farmacología , Depsidos/farmacología , Hígado/efectos de los fármacos , Hígado/patología , Alanina Transaminasa/sangre , Animales , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Intoxicación por Tetracloruro de Carbono/metabolismo , Ciclooxigenasa 2/metabolismo , Relación Dosis-Respuesta a Droga , Hígado/metabolismo , Fallo Hepático Agudo/tratamiento farmacológico , Masculino , Ratones , Ratones Endogámicos BALB C , FN-kappa B/metabolismo , Estrés Oxidativo/efectos de los fármacos , Superóxido Dismutasa/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Ácido Rosmarínico
10.
Coll Antropol ; 37(4): 1291-8, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24611347

RESUMEN

Molecular network of the osteogenic BMPs and extracellular inhibitors maintains homeostasis of the skeletal tissues. It is important to determine relationship between BMP-2, -4 and -7 and their inhibitors: gremlin, follistatin, chordin and noggin, during normal osteogenesis. To determine their expression pattern we conducted investigation by inducing ectopic bone formation in rats. The results shown that levels of the BMP-2 and BMP-4 expression in chondrocytes are similar to noggin and follistatin. The latter BMPs and inhibitors have increased levels of the expression at day 14th of the osteogenesis, which suggests their important roles in early phases of the chondrogenesis. Gremlin and chordin have shown increased levels of expression in late phase of chondrogenesis, which suggests their important role in regulation of the osteogenesis initiation. In this study, BMPs and inhibitors have the highest levels of the expression at 21st day in the osteocytes, which suggests their strong interactions in osteogenesis.


Asunto(s)
Proteína Morfogenética Ósea 2/biosíntesis , Proteína Morfogenética Ósea 4/biosíntesis , Proteína Morfogenética Ósea 7/biosíntesis , Proteínas Morfogenéticas Óseas/biosíntesis , Proteínas Portadoras/biosíntesis , Folistatina/biosíntesis , Glicoproteínas/biosíntesis , Péptidos y Proteínas de Señalización Intercelular/biosíntesis , Osteogénesis , Animales , Citocinas , Femenino , Proteínas , Ratas , Ratas Wistar
11.
Coll Antropol ; 36(2): 395-400, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22856221

RESUMEN

Pregnancy induced hypertension (PIH) is major contributor to maternal death in developing countries. Endothelin-1 (ET-1) is the most potent vasoconstriction agent known and its serum levels are increased in PIH. Therefore it is important to elucidate maternal and neonatal factors which influence endothelin-1 serum levels. 100 pathological pregnancies and 88 controls were analyzed for blood endothelin-1 and their anthropometric and clinical data were collected. In maternal blood ET-1 levels were strongly predicted by diagnosis, therapy and BMI, while umbilical cord ET-1 levels were strongly predicted by gestational age, therapy and delivery termination. Positive correlation between BMI and ET-1 levels suggest that obese pregnant women have increased risk for cardiovascular diseases. Inverse relationship between Apgar and umbilical ET-1 indicates that ET-1 could be considered as a prognostic marker in cases of neonatal asphyxia.


Asunto(s)
Antropometría , Asfixia Neonatal/sangre , Asfixia Neonatal/epidemiología , Endotelina-1/sangre , Hipertensión Inducida en el Embarazo/sangre , Hipertensión Inducida en el Embarazo/epidemiología , Adulto , Puntaje de Apgar , Femenino , Humanos , Recién Nacido , Masculino , Embarazo , Factores de Riesgo
12.
Acta Pharmacol Sin ; 33(10): 1260-70, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22902988

RESUMEN

AIM: To investigate the mechanisms underlying the protective effects of quercetin-rutinoside (rutin) and its aglycone quercetin against CCl(4)-induced liver damage in mice. METHODS: BALB/cN mice were intraperitoneally administered rutin (10, 50, and 150 mg/kg) or quercetin (50 mg/kg) once daily for 5 consecutive days, followed by the intraperitoneal injection of CCl(4) in olive oil (2 mL/kg, 10% v/v). The animals were sacrificed 24 h later. Blood was collected for measuring the activities of ALT and AST, and the liver was excised for assessing Cu/Zn superoxide dismutase (SOD) activity, GSH and protein concentrations and also for immunoblotting. Portions of the livers were used for histology and immunohistochemistry. RESULTS: Pretreatment with rutin and, to a lesser extent, with quercetin significantly reduced the activity of plasma transaminases and improved the histological signs of acute liver damage in CCl(4)-intoxicated mice. Quercetin prevented the decrease in Cu/Zn SOD activity in CCl(4)-intoxicated mice more potently than rutin. However, it was less effective in the suppression of nitrotyrosine formation. Quercetin and, to a lesser extent, rutin attenuated the inflammation in the liver by down-regulating the CCl(4)-induced activation of nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α) and cyclooxygenase (COX-2). The expression of inducible nitric oxide synthase (iNOS) was more potently suppressed by rutin than by quercetin. Treatment with both flavonoids significantly increased NF-E2-related factor 2 (Nrf2) and heme oxygenase (HO-1) expression in injured livers, although quercetin was less effective than rutin at an equivalent dose. Quercetin more potently suppressed the expression of transforming growth factor-ß1 (TGF-ß1) than rutin. CONCLUSION: Rutin exerts stronger protection against nitrosative stress and hepatocellular damage but has weaker antioxidant and anti-inflammatory activities and antifibrotic potential than quercetin, which may be attributed to the presence of a rutinoside moiety in position 3 of the C ring.


Asunto(s)
Intoxicación por Tetracloruro de Carbono/complicaciones , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Depuradores de Radicales Libres/uso terapéutico , Hígado/efectos de los fármacos , Quercetina/uso terapéutico , Rutina/uso terapéutico , Animales , Compuestos de Bifenilo/química , Intoxicación por Tetracloruro de Carbono/enzimología , Intoxicación por Tetracloruro de Carbono/patología , Enfermedad Hepática Inducida por Sustancias y Drogas/enzimología , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Relación Dosis-Respuesta a Droga , Depuradores de Radicales Libres/administración & dosificación , Depuradores de Radicales Libres/química , Inmunohistoquímica , Inyecciones Intraperitoneales , Hígado/enzimología , Hígado/patología , Pruebas de Función Hepática , Masculino , Ratones , Ratones Endogámicos BALB C , Estructura Molecular , Óxido Nítrico/química , Estrés Oxidativo/efectos de los fármacos , Picratos/química , Quercetina/administración & dosificación , Quercetina/química , Rutina/administración & dosificación , Rutina/química
13.
Coll Antropol ; 36(1): 167-72, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22816216

RESUMEN

The aim of this study was to determine whether hyperbaric oxygen (HBo2) treatment influences the expression of transcriptional myogenic factors in denervated rat's extensor digitorum longus muscle. Thus, expressing regulatory myogenic factors MyoD and myogenin were analyzed in denervated muscles (up to 30 days). Second group of denervated rats were afterwards treated with HBO2. Normal, innervated muscles were used as controls. Western blot analysis showed a significant upregulation of MyoD and myogenin proteins in denervated muscle during this period. Denervated muscles of rats exposed to HBO2 treatment had also significant upregulation of both transcriptional factors but the treatment had not altered their expression. The immunohistochemical analysis showed MyoD and myogenin protein expression through this period in the denervated, untreated muscles and in denervated muscles of rats treated with HBO2, too. One month denervation caused a reduction in muscle fiber cross-sectional area. The treatment with HBO2 had not reduced the degree of atrophy. The protocol of hyperbaric oxygenation (HBO) applied in this study had no beneficial effect either on transcriptional myogenic factors or on atrophy of denervated rat muscle.


Asunto(s)
Oxigenoterapia Hiperbárica/métodos , Desnervación Muscular/métodos , Músculo Esquelético/metabolismo , Atrofia Muscular/metabolismo , Atrofia Muscular/terapia , Factores Reguladores Miogénicos/metabolismo , Animales , Masculino , Músculo Esquelético/patología , Atrofia Muscular/patología , Ratas , Ratas Sprague-Dawley
14.
Med Hypotheses ; 78(1): 23-5, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21983351

RESUMEN

Concussion is the most common type of traumatic brain injury, with headache being the most frequent symptom of mild traumatic brain injury (MTBI) (including dizziness, vomiting, nausea, lack of motor coordination or difficulty balancing). Concussion may be caused by a blow to the head, or by acceleration forces without a direct impact. Often, MTBI occurs as the result of a sports injury. Loss of consciousness is always present, unlike vomiting. Therefore, we hypothesize vomiting to be considered as a cardinal sign of concussion. Stimulation of vomiting centres finally triggers vomiting. Professional boxers and mixed martial arts competitions reluctantly agree with stringent rules and protective clothing. We discuss the issue of further protection for those engaged in these and other sports.


Asunto(s)
Conmoción Encefálica/diagnóstico , Conmoción Encefálica/patología , Vómitos/etiología , Boxeo , Conmoción Encefálica/complicaciones , Lesiones Encefálicas/diagnóstico , Lesiones Encefálicas/patología , Diagnóstico Diferencial , Humanos , Artes Marciales
15.
Med Sci Monit ; 17(12): HY33-5, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22129908

RESUMEN

Bone morphogenetic protein-9 (BMP-9) is a member of the transforming growth factor beta (TGF-ß) superfamily of cytokines, which regulate cell growth and differentiation during embryogenesis. Apart of that, the hypoglycemic potential of BMP-9 is of great interest. It has been confirmed that BMP-9, like insulin, improves glycemia in diabetic mice and regulates directional glucose metabolism in hepatocytes; therefore it is proposed to be a candidate hepatic insulin-sensitizing substance (HISS). In liver fibrosis, due to the portocaval shunt, insulin bypasses the organ and the liver undergoes atrophy. Parenteral administration of insulin reverses atrophy by stimulating mitogenic activity of the hepatocytes. Because BMP-9 has a signaling pathway similar to other BMPs and insulin, it is to be expected that BMP-9 has a certain regenerative role in the liver, supporting the above-mentioned is evidence of BMP-9 expression in Dissè's spaces and BMP-7's mitogenic activity in mucosal cells. However, further studies are needed to confirm the possible regenerative role of BMP-9.


Asunto(s)
Factor 2 de Diferenciación de Crecimiento/metabolismo , Regeneración Hepática/fisiología , Animales , Humanos , Ratones , Modelos Biológicos
16.
Med Hypotheses ; 77(5): 927-9, 2011 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-21890279

RESUMEN

Recent understandings of the vascular contribution of pathophysiology of osteoarthritis (OA) mount new evidence of cross-talking between subchondral bone tissue and articular cartilage that might have a decisive role in a pathophysiology of Osteoarthritis (OA). These understandings include blood flow (or interstitial fluid) impairment in subchondral bone. With regard to the mentioned role of the vasculature, the absence of custom nourishing to articular cartilage, and established, vasoconstrictive role of endothelin-1 (ET-1) it was reasonable to assume that ET-1 has an inconvertible role in pathophysiology of OA. Another moment in pathophysiology of OA is apoptosis of subchondral osteocytes, what induces osteoclastic resorption and at least temporarily reduces the bony support for the overlying cartilage. Since regional dependence of this protein's expression was presumed, we suggest a regional division of subchondral bone by histomorphometrical analysis and quantification of identified protein by Real Time Polymerase Chain Reaction Analysis (RT-PCR). Obtained results should be compared to serum levels of soluble ET-1, what would enforce this methods validity. Herewith, a new screening marker of patients with osteoarthritis would be established. This would enable detection and follow-up of groups threatened by this, growing, cause of disability and decreased quality of life.


Asunto(s)
Huesos/patología , Endotelina-1/genética , Osteoartritis/genética , Osteoartritis/patología , ARN Mensajero/genética , Humanos , Reacción en Cadena en Tiempo Real de la Polimerasa
17.
J Clin Densitom ; 13(1): 36-42, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20171567

RESUMEN

Bone loss is a common problem for individuals with inflammatory bowel disease (IBD). The aim of our study was to assess bone mineral density (BMD) in patients with IBD and to investigate the role of corticosteroid (CS) use and duration and activity of disease on BMD. Ninety-two patients (56 men and 36 women) with IBD, of whom 32 had ulcerative colitis (UC) and 60 had Crohn's disease (CD), underwent clinical assessment. Lumbar and femoral neck BMDs were measured by dual-energy X-ray absorptiometry. Osteopenia was observed in 14 patients (43%) with UC and in 24 patients (40%) with CD (p=0.187). Four patients (12%) with UC and 7 patients (11%) with CD had osteoporosis (p=0.308). Femoral BMD decreased in patients with long duration of CS use and correlated inversely with disease activity. Multiple regression analysis of BMD showed that statistically significant risk factors were duration of active disease and body mass index as well. Based on our results, it is necessary to take into account the risk of decreased BMD in patients with IBD. It is most important to achieve disease remission as soon as possible in addition to nutritional support.


Asunto(s)
Absorciometría de Fotón/métodos , Densidad Ósea , Resorción Ósea/etiología , Fémur/metabolismo , Enfermedades Inflamatorias del Intestino/complicaciones , Vértebras Lumbares/metabolismo , Adulto , Anciano , Resorción Ósea/diagnóstico por imagen , Resorción Ósea/metabolismo , Progresión de la Enfermedad , Femenino , Fémur/diagnóstico por imagen , Estudios de Seguimiento , Humanos , Enfermedades Inflamatorias del Intestino/metabolismo , Vértebras Lumbares/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Osteoporosis/diagnóstico por imagen , Osteoporosis/etiología , Osteoporosis/metabolismo , Pronóstico , Estudios Retrospectivos , Factores de Tiempo , Adulto Joven
18.
Coll Antropol ; 34 Suppl 2: 105-8, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21305730

RESUMEN

Aging is associated with loss of skeletal muscle mass, strength and endurance. The aim of this study was to determinate age related changes in human muscles with different function and location in the body (vastus lateralis muscle and intercostal internus muscle). Our results suggest that age related muscle atrophy affect both human skeletal muscles. Also, the results showed the increase in percentage of muscle fibers with high oxidative activity during aging.


Asunto(s)
Envejecimiento/patología , Músculos Intercostales/patología , Atrofia Muscular/patología , Músculo Cuádriceps/patología , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Fibras Musculares de Contracción Rápida/patología , Fibras Musculares de Contracción Lenta/patología , Adulto Joven
19.
Coll Antropol ; 34 Suppl 2: 161-8, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21302716

RESUMEN

The concept of bone quality describes the sets of the characteristics of the osseous tissue that influence bone strength. The aim was to explore the influence of anthropometric parameters and age on the parameters of the bone architecture and bone mineral properties in the lumbar vertebral bone of men and women. Vertebral bone samples underwent bone histomorphometry, bone densitometry and atomic absorption spectrometry. Men have greater values of the bone volume and thicker bone trabeculae in relation to women, which indicates that vertebral bone architecture is better preserved in men than in women. Age is the best predictor of changes that affect bone architecture and bone mineral properties. Bone mineral density value and calcium concentration are both negatively predicted by age, but positively predicted by body mass index. Such result supports the opinion that low body mass index is associated with conditions of bone deficit such are osteopenia and osteoporosis.


Asunto(s)
Constitución Corporal/fisiología , Densidad Ósea/fisiología , Enfermedades Óseas Metabólicas/fisiopatología , Osteoporosis/fisiopatología , Espectrofotometría Atómica/métodos , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Antropometría , Índice de Masa Corporal , Enfermedades Óseas Metabólicas/diagnóstico , Femenino , Humanos , Vértebras Lumbares/fisiología , Masculino , Persona de Mediana Edad , Osteoporosis/diagnóstico , Valor Predictivo de las Pruebas , Factores Sexuales
20.
Coll Antropol ; 34 Suppl 2: 169-73, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21302717

RESUMEN

The aim of our study was to explore the age related changes of the fibre type composition of the human psoas major muscle. Moreover, we wanted to compare the fibre type composition of the left and right muscle. Muscle samples were collected from 15 young and 15 old males. Type I, IIA and IIX muscle fibres were typed using myosin heavy chain identification. The serial transverse sections were analysed using a light microscope. Results of our study showed that the age-related atrophy affected all three fibre types. Type IIA fibres were affected most profoundly while type I fibres were affected most weakly. The percentage of the different fibre types did not change during aging. There were no differences in the fibre type composition between the left and right muscle. Human psoas major muscle undergoes normal aging changes with the atrophy of all three fibre types, whereas atrophy most profoundly affects type IIA fibres. No differences in the fibre type composition between the left and right muscle point to the equal engagement of both legs in normal everyday activities of human.


Asunto(s)
Envejecimiento/metabolismo , Envejecimiento/patología , Inmunohistoquímica/métodos , Músculos Psoas/citología , Músculos Psoas/metabolismo , Adulto , Anciano , Humanos , Masculino , Fibras Musculares de Contracción Rápida/citología , Fibras Musculares de Contracción Rápida/metabolismo , Fibras Musculares de Contracción Lenta/citología , Fibras Musculares de Contracción Lenta/metabolismo , Atrofia Muscular/metabolismo , Atrofia Muscular/patología , Cadenas Pesadas de Miosina/metabolismo
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