Protective Effect of Baccharis trimera Extract on Acute Hepatic Injury in a Model of Inflammation Induced by Acetaminophen

Background. Acetaminophen (APAP) is a commonly used analgesic and antipyretic. When administered in high doses, APAP is a clinical problem in the US and Europe, often resulting in severe liver injury and potentially acute liver failure. Studies have demonstrated that antioxidants and anti-inflammatory agents effectively protect against the acute hepatotoxicity induced by APAP overdose. Methods. The present study attempted to investigate the protective effect of B. trimera against APAP-induced hepatic damage in rats. The liver-function markers ALT and AST, biomarkers of oxidative stress, antioxidant parameters, and histopathological changes were examined. Results. The pretreatment with B. trimera attenuated serum activities of ALT and AST that were enhanced by administration of APAP. Furthermore, pretreatment with the extract decreases the activity of the enzyme SOD and increases the activity of catalase and the concentration of total glutathione. Histopathological analysis confirmed the alleviation of liver damage and reduced lesions caused by APAP. Conclusions. The hepatoprotective action of B. trimera extract may rely on its effect on reducing the oxidative stress caused by APAP-induced hepatic damage in a rat model. General Significance. These results make the extract of B. trimera a potential candidate drug capable of protecting the liver against damage caused by APAP overdose

Extrato de urucum e β-caroteno alteram a sinalização redox em neutrófilos de ratas diabéticas através da regulação da expressão gênica da NADPH oxidase, superóxido dismutase e catalase.

Urucum (Bixa orellana L.) contém uma mistura de pigmentos amarelo-avermelhado devido à presença de vários carotenóides que possuem efeito antioxidante. É bem estabelecido que um dos elementos chave no desenvolvimento das complicações do diabetes é o estresse oxidativo. O sistema imunológico é vulnerável a danos oxidativos, porque algumas células desse sistema, tais como neutrófilos, produzem espécies reativas de oxigênio (EROs) e espécies reativas de nitrogênio (ERNs) como parte dos mecanismos de defesa do organismo para destruir os patógenos invasores. EROs/ERNs são produzidos excessivamente por neutrófilos podendo danificar componentes celulares essenciais e dessa forma causar as complicações vasculares no diabetes. Esse estudo avaliou os possíveis efeitos protetores do extrato de urucum sobre as EROs, óxido nítrico (NO) e sobre os mecanismos regulatórios envolvidos neste processo em neutrófilos de ratas diabéticas induzidas por aloxano. Foram feitos dois experimentos, com duração de 30 ou 7 dias, e em cada foram utilizados 48 ratas que foram divididas em seis grupos, a saber: controle (C), controle + extrato de urucum (CUr), controle + β-caroteno (Cβcar), diabético (D), diabético + extrato de urucum (DUr) e diabético + β-caroteno (Dβcar). O diabetes foi induzido com uma injeção intraperitoneal única de aloxano (150 mg/Kg). Os animais dos grupos C e D receberam dieta padrão (AIN-93M) e os grupos CUr, Cβcar, DUr e Dβcar receberam dieta padrão suplementada com 0,1% de extrato de urucum ou β-caroteno. Todos os animais foram sacrificados 30 ou 7 dias depois do início do tratamento e os neutrófilos foram isolados usando dois gradientes de densidade diferentes. As EROs e NO foram quantificados por ensaios de quimioluminescência ou espectrofotometria, respectivamente. No experimento de 30 dias, nossos resultados mostraram que os neutrófilos de animais diabéticos produziram significativamente mais EROs e NO do que seus respectivos controle e a suplementação com extrato de urucum ou β-caroteno foi capaz de modular a produção dessas espécies reativas. No experimento de 7 dias, os resultados mostraram que o tratamento com extrato de urucum ou β-caroteno foi capaz de diminuir a produção de EROs, os níveis de mRNA de p22phox e p47phox e aumentar a expressão do mRNA e a atividade de SOD e catalase em neutrófilos de ratas diabéticas. Esses resultados sugerem que o extrato de urucum e o β-caroteno possuem efeito antioxidante via inibição das subunidades da NADPH oxidase e aumento da atividade e expressão das enzimas antioxidantes. O extrato de urucum pode ter um potencial terapêutico na modulação do balanço EROs/NO induzidos pelo diabetes.Annatto (Bixa orellana L.) contain a mixture of orange-yellowish pigments due to the presence of various carotenoids that have antioxidant effect. It is well known that one of the key elements in the development of diabetic complications is oxidative stress. The immune system is especially vulnerable to oxidative damage because many immune cells, such as neutrophils, produce reactive oxygen species (ROS) and reactive nitrogen species (RNS) as part of the body's defense mechanisms to destroy invading pathogens. ROS/RNS are excessively produced by active peripheral neutrophils, and may damage essential cellular components, which in turn can cause vascular complications in diabetes. The present study was undertaken to evaluate the possible protective effects of annatto on the ROS, nitric oxide (NO) and the regulatory mechanisms involved in this process in neutrophils from alloxan-induced diabetic rats. Two experiments were made, lasting 30 and 7 days each, andwere used for each of 48 rats divided into six groups, control (C), control + annatto extract (CAn), control + β-carotene (Cβcar), diabetic (D), diabetic + annatto extract (DAn) and diabetic + β-carotene (Dβcar). Diabetes was induced by a single intraperitoneal injection of alloxan (150 mg / kg). Animals in groups C and D received a standard diet (AIN-93M) those in groups CAn, DAn, Cβcar, Dβcar received a standard diet plus 0.1% of annatto extract or β-carotene. All animals were sacrificed 30 or 7 days after treatment and the neutrophils were isolated using two gradients of different densities. The ROS and NO were quantified by a chemiluminescence and spectrophotometric assays, respectively. In the experiment of 30 days, our results show that neutrophils from diabetic animals produce significantly more ROS and NO than their respective controls and that supplementation with annatto extract and beta carotene was able to modulate the production of these species. In the experiment of 7 days, the results show that treatment with annatto extract and β-carotene was able to decrease ROS production and the mRNA levels of p22 phox and p47 phox and increase the mRNA levels of SOD and catalase in neutrophils from diabetic rats. These data suggest that annatto extract and β-carotene exerts antioxidant effect via inhibition of expression of the NADPH oxidase subunits and increase expression/activity of antioxidant enzymes. Annatto extract may have therapeutic potential for modulation of the balance ROS/NO induced by diabetes

Perfil lipídico, defesas antioxidantes e marcadores de função hepática e renal em hamsteres tratados com extratos de sementes de urucum.

O urucum (Bixa orellana L.) tem sido descrito pela comunidade científica por seu efeito hipocolesterolemiante. Dessa forma o objetivo desse trabalho foi avaliar o efeito da infusão aquosa do urucum (Bixa orellana L) e da torta de bixina sobre o perfil lipídico, defesas antioxidantes e marcadores de função hepática e renal em hamsteres. Foram utilizados 64 hamsteres machos Golden Syrian que foram distribuídos em oito grupos: controle (C) recebeu dieta padrão (AIN-93 M), H recebeu dieta hipercolesterolemiante, CCh recebeu dieta padrão e infusão aquosa de urucum, HCh recebeu dieta hipercolesterolemiante e infusão aquosa de urucum, CB15 recebeu dieta padrão contendo 0,015% de torta de bixina, HB15 recebeu dieta hipercolesterolemiante contendo 0,015% de torta de bixina, CB75 recebeu dieta padrão contendo 0,075% de torta de bixina e HB75 recebeu dieta hipercolesterolemiante contendo 0,075% de torta de bixina. Amostras de sangue foram coletadas após oito semanas de experimento para realização as dosagens bioquímicas. Nos grupos hipercolesterolemiantes tratados com bixina, mas não nos que receberam dieta padrão tratados com bixina observamos um aumento dos níveis séricos de colesterol total, colesterol não-HDL, da fração HDL do colesterol, do colesterol hepático e da porcentagem de gordura nas fezes. Observamos uma diminuição dos triacilgliceróis nos grupos CB15, CB75 e HB75. A atividade da aspartato aminotransferase foi diminuída nos grupos que receberam dieta hipercolesterolemiante contendo 0,015% e 0,075% de torta de bixina. O tratamento com a torta de bixina aumentou atividade da ALP nos grupos CB15, HB15 e HB75 e na concentração de creatinina nos grupos CCh, CB15, CB75 e HB75. A atividade da paraoxonase apresentou-se diminuída nos grupos CCh, CB15 e CB75. A concentração de sulfidrilas ligadas a fração protéica aumentou 50% nos grupos CB15 e CB75 e uma diminuição de 30% nos grupos HB15 e HB75. A atividade da catalase aumentou nos grupos CB15 e HB15 e a atividade da paraoxonase apresentou-se diminuída nos grupos CCh, CB15 e CB75. Nossos dados indicam que no modelo experimental proposto e na concentração utilizada de torta de bixina houve um aumento na concentração sérica do colesterol nos grupos hipercolesterolemiantes não corroborando, dessa forma com os dados encontrados na literatura. Não observamos efeito protetor hepático e renal da torta de bixina nos hamsteres.Annatto seeds (Bixa orellana L.) are known to the scientific community for their hypocholesterolemic effects. This study aimed to evaluate the aqueous infusion effect of the annatto (Bixa orellana L.) and bixin cake about on the lipid profile, antioxidant defenses and markers of the hepatic and renal function in hamsteres. Eigth groups were formed containing eight male Golden Syrian hamsters each. The group control (C) received the standard (AIN-93 M) diet, H received a hypercholesterolemic diet, CCh received standard diet and aqueous annatto infusion, HCh received hypercholesterolemic diet and aqueous annatto infusion, CB15 received standard diet containing 0,015% of bixin cake, HB15 received hypercholesterolemic diet containing 0,015% of bixin cake, the group CB75 received a standard diet containing 0,075% of bixin cake and the group HB75 received a hypercholesterolemic diet with 0,075% of bixin cake. Samples of blood were collected after eight weeks of experiment so that the biochemical dosages were made. In the groups hypercholesterolemic treated with bixin, that don‟t received standard diet treated with bixin cake, we observed an increase of the serum levels of cholesterol, non-HDL cholesterol, HDL cholesterol, liver cholesterol and the fat percentage in the feces. In groups CB15, CB75 and HB75 diminished levels of triacylglycerols were found. Aspartate aminotransferase activity was decreased amongst the animals receiving the hypercholesterolemic diet containing both levels of bixin cake. The treatment with this roduct increased the activity of alkaline phosphatase in groups CB15, HB15 and HB75 as compared to groups C and H and in the creatinine concentration in the groups CCh, CB15, CB75 and HB75. Sulphydryl concentration in serum proteins increased 50% in CB15 and CB 75 in relation to the controls but decreased 30% in groups HB15 and HB75 in relation to H. Catalase activity increased in groups CB15 and HB15. Paraoxonase activity was found to be lower in the CCh, CB15 and CB75 animals as compared to the controls. Our data indicate that in the experimental model proposed and in the utilized level of bixin cake there was an increase in the concentration of serum cholesterol in the hypercholesterolemic groups and this does not corroborate with results found in the literature. We didn't observe hepatic and renal protecting effect of the bixin cake in the hamsters

Effect of an aqueous extract of annatto (Bixa orellana) seeds on lipid profile and biochemical markers of renal and hepatic function in hipercholesterolemic rats.

Annatto extract is a natural food color obtained from the outer coatings of the seeds of the Annatto tree (Bixa orellana L.). This is the first report in the literature that shows the relationship between the aqueous annatto extract and its influence on lipid profile in animals. Male Fisher rats were divided into three groups (n=12): C group, fed standard diet and water; H group, fed high-lipid diet and water and; HU group, with high-lipid diet and aqueous annatto extract for 60 days. The treatment with annatto extract in animals fed with the high-lipid diet lowered the LDL- and total cholesterol and raised the HDL-cholesterol, suggesting a hypocholesterolemic effect. Neither highfat diet nor aqueous annatto extract had any significant effect on serum levels of albumin or serum activities of transaminases which suggested that no liver injury was induced

Antioxidant properties of Baccharis trimera in the neutrophils of Fisher rats.

Ethnopharmacological relevance: Baccharis trimera (Less.) (Asteraceae) is a native plant of Brazil. Also known as “carqueja”, it has been popularly used to treat liver diseases, diabetes, as well as digestive disorders. Other studies have described the hepatoprotective, antioxidant and anti-inflammatory activities of the species. Aim of the study: The aim of the present study was to investigate the antioxidant properties of Baccharis trimera in the neutrophils of Fisher rats in both in vitro and in vivo experimental models. Material and methods: In the in vitro assay, the neutrophils of male rats were isolated and incubated with Baccharis trimera extract at concentrations of 0.5, 5.0 and 50.0_g/mL. In the in vivo assay, male rats were first treated with crude extract 600 mg/kg body weight of Baccharis trimera or with 50 mg/kg body weight of quercetin (reference substance) and then treated with 835 mg/kg of acetaminophen (APAP) after 24 h. Results: The hydroethanolic extract of Baccharis trimera reduced the release of reactive oxygen species in the neutrophils in both the in vitro and in vivo experimental models. Therefore confirming its antioxidant effect. Conclusion: The results of this study confirm the antioxidant effect of Baccharis trimera

Physical activity prevents alterations in mitochondrial ultrastructure and glucometabolic parameters in a high-sugar diet model

<div><p>Endurance exercise is a remarkable intervention for the treatment of many diseases. Mitochondrial changes on skeletal muscle are likely important for many of the benefits provided by exercise. In this study, we aimed to evaluate the effects that a regular physical activity (swimming <i>without</i> workload) has on mitochondrial morphological alterations and glucometabolic parameters induced by a high-sugar diet (HSD). Weaned male Wistar rats fed with a standard diet or a HSD (68% carbohydrate) were subjected to 60 minutes of regular physical activity by swimming (<i>without</i> workload) for four- (20 sessions) or eight-week (40 sessions) periods. After training, animals were euthanized and the sera, adipose tissues, and skeletal muscles were collected for further analysis. The HSD increased body weight after an 8-week period; it also increased the fat pads and the adipose index, resulting in glucose intolerance and insulin resistance (IR). Transmission electron microscopy showed an increase in alterations of mitochondrial ultrastructure in the gastrocnemius muscle, as well as a decrease in superoxide dismutase (SOD) activity, and an increase in protein carbonylation. Regular physical activity partially reverted these alterations in rats fed a HSD, preventing mitochondrial morphological alterations and IR. Moreover, we observed a decrease in <i>Pgc1α</i> expression (qPCR analysis) in STD-EXE group and a less pronounced reduction in HSD-EXE group after an 8-week period. Thus, regular physical activity (swimming <i>without</i> workload) in rats fed a HSD can prevent mitochondrial dysfunction and IR, highlighting the crucial role for physical activity on metabolic homeostasis.</p></div

Characteristics of rats fed a STD or HSD in a 4-week period.

<p>Characteristics of rats fed a STD or HSD in a 4-week period.</p