Effects of the interaction of diabetes and iron supplementation on hepatic and pancreatic tissues, oxidative stress markers, and liver peroxisome proliferator-activated receptor-α expression

This study evaluated the effects of the interaction of diabetes and a carbonyl iron supplemented on hepatic and pancreatic tissues, oxidative stress markers and liver peroxisome proliferator-activated receptor-α expressions. Hamsters were divided: Control which received a standard AIN 93 diet; Control Iron, composed of control animals that received a diet with 0.83% carbonyl iron; Diabetic, composed of animals that received a injection of streptozotocin (50 mg/kg, intraperitoneal) on day 35; and Diabetic Iron composed of streptozotocin treated animals that received a diet supplemented with carbonyl iron. Diabetes increased the glucose level and reduced triglycerides. Diabetic Iron group showed higher levels of glucose and serum triglycerides as compared to the Diabetic group. Diabetes decreased mRNA levels of peroxisome proliferator-activated receptor-α. Iron attenuated the diabetes induced down regulation of peroxisome proliferator-activated receptor-α mRNA. Moreover, diabetes increased carbonyl protein and decreased glutathione levels and catalase activity, while iron attenuated the increase in levels of carbonyl protein and attenuated the decrease in those of glutathione level and catalase activity. Histological analysis shows that supplementation iron caused an increase in the size of the islets in Control Iron. The results show that iron does not aggravated liver oxidant/antioxidant status and peroxisome proliferator-activated receptor-α expression in diabetic hamsters

Carqueja (Baccharis trimera) Protects against Oxidative Stress and -Amyloid-Induced Toxicity in Caenorhabditis elegans

Carqueja (Baccharis trimera) is a native plant found throughout South America. Several studies have shown that Carqueja has antioxidant activity in vitro, as well as anti-inflammatory, antidiabetic, analgesic, antihepatotoxic, and antimutagenic properties. However, studies regarding its antioxidant potential in vivo are limited. In this study, we used Caenorhabditis elegans as a model to examine the antioxidant effects of a Carqueja hydroalcoholic extract (CHE) on stress resistance and lifespan and to investigate whether CHE has a protective effect in a C. elegans model for Alzheimer's disease. Here, we show for the first time, using in vivo assays, that CHE treatment improved oxidative stress resistance by increasing survival rate and by reducing ROS levels under oxidative stress conditions independently of the stress-related signaling pathways (p38, JNK, and ERK) and transcription factors (SKN-1/Nrf and DAF-16/Foxo) tested here. CHE treatment also increased the defenses against -amyloid toxicity in C. elegans, in part by increasing proteasome activity and the expression of two heat shock protein genes. Our findings suggest a potential neuroprotective use for Carqueja, supporting the idea that dietary antioxidants are a promising approach to boost the defensive systems against stress and neurodegeneration

O extrato aquoso de açaí (Euterpe oleracea Mart) modula a resistência ao estresse oxidativo no organismo modelo Caenorhabditis elegans através de mecanismos diretos e indiretos.

Programa de Pós-Graduação em Ciências Biológicas. Núcleo de Pesquisas em Ciências Biológicas, Pró-Reitoria de Pesquisa e Pós Graduação, Universidade Federal de Ouro Preto.O açaí (Euterpe oleracea Mart.) surgiu recentemente como uma promissora fonte de antioxidantes naturais. Apesar de seu valor como alimento funcional, estudos sobre os efeitos do açaí in vivo são ainda limitados. Neste trabalho, utilizamos o modelo Caenorhabditis elegans para avaliar as propriedades antioxidantes do açaí in vivo e para desvendar seu mecanismo de ação. A suplementação com 100 mg/mL do extrato aquoso de açaí (EAA) por 48 horas aumentou tanto a resistência ao estresse oxidativo quanto a resistência ao estresse osmótico independentemente de qualquer efeito na reprodução e no desenvolvimento dos animais. O tratamento com EAA inibiu o crescimento bacteriano, mas esta propriedade antimicrobiana não influenciou a resistência ao estresse oxidativo. O aumento da resistência ao estresse oxidativo mediado pelo EAA apresentou correlação com a redução da produção de ERO, prevenção da redução de grupos sulfidrilas (SH) e da ativação de gcs-1 observadas em condições de estresse oxidativo. Nossos estudos mecanísticos demonstraram que o EAA promove resistência ao estresse oxidativo, agindo de maneira dependente de DAF-16 e da via de sinalização ativada em resposta ao estresse osmótico OSR-1/UNC-43/SEK-1. Finalmente, o EAA aumentou a agregação de proteínas com expansões poliglutamínicas e diminuiu a atividade do proteassoma. Os resultados obtidos sugerem que os compostos naturais presentes no EAA podem melhorar a capacidade antioxidante de um organismo, sob condições de estresse, por mecanismos diretos e indiretos.Açaí (Euterpe oleracea Mart.) has recently emerged as a promising source of natural antioxidants. Despite its value as a functional food, studies regarding the effects of açaí in vivo are limited. In this study, we use the Caenorhabditis elegans model to evaluate the in vivo antioxidant properties of açaí on an organismal level and to examine its mechanism of action. Supplementation with açaí aqueous extract (AAE) increased both oxidative and osmotic stress resistance independently of any effect on reproduction and development. AAE suppressed bacterial growth, but this antimicrobial property did not influence stress resistance. AAE-increased stress resistance was correlated with reduced ROS production, the prevention of sulfhydryl (SH) level reduction and gcs-1 activation under oxidative stress conditions. Our mechanistic studies indicated that AAE promotes oxidative stress resistance by acting through DAF-16 and the osmotic stress response pathway OSR-1/UNC-43/SEK-1. Finally, AAE increased polyglutamine protein aggregation and decreased proteasome activity. These findings suggest that natural compounds available in AAE can improve the antioxidant status of a whole organism under certain conditions by direct and indirect mechanisms

Excesso de ferro altera o status oxidativo, a homeostase de colesterol e glicose e a expressão de PPAR-α em hamsteres.

Dietas ricas em lipídios, obesidade e estresse oxidativo estão relacionadas ao desenvolvimento de diabetes tipo II e doenças cardiovasculares. Estoques elevados de ferro podem promover aumento da formação de radicais livres e do estresse oxidativo, favorecendo, assim, o desenvolvimento dessas doenças, como se observa em populações com estoques aumentados de ferro. Portanto, este estudo objetivou avaliar o efeito do excesso de ferro, da dieta rica em lipídios e da interação entre as duas variáveis sobre fatores de risco para doenças cardiovasculares: lipídios séricos, estresse oxidativo e glicemia. Além disso, foram analisadas a expressão de ácido ribonucleico menssageiro (RNAm) de genes relacionados ao metabolismo de lipídios e a produção de radicais livres por granulócitos. Foram distribuídos 52 hamsteres Golden Syrian machos em quatro grupos: C e CF receberam dieta padrão e H e HF receberam dieta hipercolesterolemiante. Os grupos CF e HF receberam injeções de ferro dextran (doses diárias de 10 mg durante cinco dias) no 45º dia de experimento. Ao final de 60 dias, os hamsteres foram eutanasiados para coleta de sangue e tecidos. Os dados foram submetidos à análise de variância (ANOVA). Diferenças de p<0,05 foram consideradas significativas. Como esperado, a dieta rica em lipídios promoveu aumento sérico do colesterol total e suas frações, além de redução na atividade da paraoxonase (PON). O tratamento com ferro aumentou os níveis séricos e hepáticos de ferro. Observou-se aumento da quantidade hepática de glutationa e da atividade sérica da superóxido dismutase, bem como redução da atividade hepática da catalase nos grupos CF, H e HF, sendo o efeito mais pronunciado no grupo HF. O tratamento com ferro ainda aumentou a quantidade de substâncias que reagem com o ácido tiobarbitúrico (TBARS) no fígado e nos rins e a produção de radicais livres por granulócitos. O ferro potencializou o efeito hipercolesterolêmico da dieta, uma vez que o grupo HF apresentou valores séricos de colesterol total superiores ao H (5,81 ± 0,57 e 4,59 ± 0,32, respectivamente). A análise de expressão gênica por reação em cadeia da polimerase quantitativa (qPCR) de receptor ativador da proliferação peroxissomal (PPAR-α), receptor nuclear importante no controle da homeostase de lipídios e carboidratos, mostrou que o grupo HF apresentou expressão relativa menor que o grupo H. A homeostase de glicose também foi alterada: os animais que receberam tratamento com ferro exibiram porcentagem de hemoglobina glicosilada superior à dos animais não tratados e tiveram alterações na tolerância à glicose. Concluiu-se que o excesso de ferro aumenta o estresse oxidativo e interfere na homeostase de colesterol e glicose. Esses efeitos podem ser, em parte, atribuídos à diminuição na expressão do RNAm de PPAR- α.Diets rich in lipids, obesity and oxidative stress are related to the development of type II diabetes and cardiovascular diseases. Iron overload increases formation of free radicals and oxidative stress, thus promoting the development of these diseases, as has been observed in populations with high iron stores. In this study we evaluated the effect of iron overload, high fat diet and the interaction between these two variables on risk factors for cardiovascular disease: serum lipids, oxidative stress and blood glucose. In addition, we also analyzed the expression level of genes related to lipid metabolism and free radical production by granulocytes. Fifty-two male Golden Syrian hamsters were divided into four groups: C and CI received a standard diet while H and HI received high fat diet. CI and HI groups were given injections of iron dextran (daily doses of 10mg for five days) at the 45th day of experiment. After 60 days, hamsters were euthanized and blood and tissue were collected for further investigation. Data were analyzed by variance analysis (ANOVA). p <0.05 were considered significant. As expected the high fat diet caused an increase in total cholesterol and its fractions, and a reduction in paraoxonase activity (PON) and iron treatment increased serum and liver iron stores. There was an increase of hepatic glutathione levels and serum superoxide dismutase activity and a reduction of hepatic catalase activity in the CI groups, H and HI, which was more pronounced in the HI group. Iron treatment also increased the amount of liver and kidney TBARS and free radicals production by granulocytes. Iron acted synergically with the high fat diet, as HI group had serum total cholesterol higher than H (5.81 ± 0.57 and 4.59 ± 0.32 respectively). Gene expression analysis by qPCR of PPAR-α, important nuclear receptor in controlling lipid and carbohydrate homeostasis, showed that HI group had lower expression than H. Glucose homeostasis was also altered and the animals treated with iron showed greater glycated hemoglobin percentage than untreated animals, and had abnormal glucose tolerance. These data suggest that iron overload increases oxidative stress and interferes on cholesterol and glucose homeostasis. These effects can be, in part, attributed to the decreasing of PPAR-α expression

Iron overload potentiates diet-induced hypercholesterolemia and reduces liver PPAR-α expression in hamsters.

Iron stores and lipids are related to the development of cardiovascular disease. Given that peroxisome proliferator-activated receptor alpha (PPAR-α) regulates important physiological processes that impact lipid and glucose homeostasis, we decided to investigate the effects of iron overload on serum lipids and the liver expression of PPAR-α, 3-hydroxy- 3-methylglutaryl coenzyme A reductase, and cholesterol 7α-hydroxylase. Hamsters were divided into four groups. The standard group (S) was fed the AIN-93M diet, the SI group was fed the diet and iron injections, the hypercholesterolemic group (H) was fed a standard diet containing cholesterol, and the HI group was fed a high-cholesterol diet and iron injections. Serum cholesterol in the HI group was higher than in the H group. Gene expression analysis of PPAR-α showed that the HI group had a lower PPAR-α expression than H. These data show that iron, when associated with a high-fat diet, can cause increased serum cholesterol levels, possibly due to a reduction in PPAR- α expression

Iron overload potentiates diet-induced hypercholesterolemia and reduces liver ppar-? expression in hamsters.

Iron stores and lipids are related to the development of cardiovascular disease. Given that peroxisome proliferator-activated receptor alpha (PPAR-?) regulates important physiological processes that impact lipid and glucose homeostasis, we decided to investigate the effects of iron overload on serum lipids and the liver expression of PPAR-?, 3-hydroxy- 3-methylglutaryl coenzyme A reductase, and cholesterol 7?-hydroxylase. Hamsters were divided into four groups. The standard group (S) was fed the AIN-93M diet, the SI group was fed the diet and iron injections, the hypercholesterolemic group (H) was fed a standard diet containing cholesterol, and the HI group was fed a high-cholesterol diet and iron injections. Serum cholesterol in the HI group was higher than in the H group. Gene expression analysis of PPAR-? showed that the HI group had a lower PPAR-? expression than H. These data show that iron, when associated with a high-fat diet, can cause increased serum cholesterol levels, possibly due to a reduction in PPAR- ? expression

El a?ai mejora la enfermedad de h?gado graso no alcoh?lico (NAFLD) inducida por la fructosa.

Introduction: the excessive consumption of fructose can cause liver damage, characteristic of non-alcoholic fatty liver disease (NAFLD) associated with changes in lipid metabolism and antioxidant defenses. A?ai, the fruit of Euterpe oleracea Mart., has demonstrated numerous biological activities, including anti-inflammatory, antioxidant, and lipid metabolism modulating action. Objective: we evaluated the benefits of a?ai supplementation on liver damage caused by replacing starch with fructose in rats. Methods: thirty male Fischer rats were divided into two groups, the control group (C, 10 animals), which consumed a standard diet (AIN-93M), and the fructose (F, 20 animals) group, which consumed a diet containing 60% of fructose. After eight weeks, 10 animals from the fructose group received 2% of lyophilized a?ai, and were called the a?ai fructose group (FA). The animals were fed ad libitum with these diets for another ten weeks. Serum, hepatic and fecal lipid profile, antioxidant enzymes and carbonylated protein were assessed and histopathological characterization of the liver was performed. Results: a?ai promoted the reduction of ALT activity in relation to the fructose group (F), reduced alkaline phosphatase to a level similar to that of the control group (C) in relation to the fructose group (F), and reduced catalase activity. The fruit also increased the ratio of total/oxidized glutathione (GSH/GSSG) and reduced the degree of macrovesicular steatosis and the number of inflammatory cells. Conclusion: the replacement of starch by fructose during this period was effective in promoting NAFLD. A?ai showed attenuating effects on some markers of hepatic steatosis and inflammation.Introducci?n: el consumo excesivo de fructosa puede causar da?o hep?tico, caracter?stico de la enfermedad hep?tica grasa no alcoh?lica (EHGNA), asociada con cambios en el metabolismo de los l?pidos y defensas antioxidantes. El a?ai, fruto del Euterpe oleracea Mart., ha demostrado desempe?ar numerosas actividades biol?gicas, incluidas acciones antiinflamatorias, antioxidantes y moduladoras del metabolismo lip?dico. Objetivo: se evaluaron los beneficios de la suplementaci?n con a?ai en el da?o hep?tico causado por la sustituci?n del almid?n por fructosa en ratas. M?todos: se distribuyeron 30 ratas Fischer macho en dos grupos: 10 ratas en el grupo control (C), que consum?a una dieta est?ndar (AIN-93M), y 20 ratas en el grupo fructosa (F), que consum?a una dieta que conten?a un 60% de fructosa. Despu?s de ocho semanas, diez animales del grupo fructosa recibieron un 2% de a?ai liofilizado, por lo que pasaron a integrar el grupo a?ai fructosa (FA). Los animales fueron alimentados ad libitum con estas dietas durante otras diez semanas. Se analizaron el perfil lip?dico hep?tico y fecal, las enzimas antioxidantes y la prote?na carbonilada, y se realiz? la caracterizaci?n histopatol?gica del h?gado. Resultados: el a?ai promovi? la reducci?n de la actividad de ALT en relaci?n al grupo de fructosa (F) y la reducci?n de la fosfatasa alcalina a niveles similares a los hallados en el grupo control (C) en relaci?n con el grupo de fructosa (F). El fruto tambi?n aument? la proporci?n de glutati?n total/oxidado (GSH/GSSG) y redujo el grado de esteatosis macrovesicular y el n?mero de c?lulas inflamatorias. Conclusi?n: la sustituci?n de almid?n por fructosa durante este periodo fue eficaz en la promoci?n de NAFLD. El a?ai mostr? efectos atenuantes en algunos marcadores de esteatosis hep?tica y de inflamaci?n