Astaxanthin improves lipotoxicity, lipid peroxidation and oxidative stress in kidney of sucrose-rich diet-fed rats.

Metabolic Syndrome (MS) is a cluster of metabolic risk factors, characterized by abdominal obesity, dyslipidemia, hypertension, insulin resistance, among others. The purpose of the study was to evaluate the astaxanthin (AXT) effects extracted from freshwater crab (Dilocarcinus pagei) at the Paraná Basin on lipotoxicity, lipid peroxidation and oxidative stress in the kidney of rats fed with a sucrose-rich diet (SRD). We hypothesized that daily administration of AXT prevents kidney damage by reducing lipotoxicity, lipid peroxidation, and reactive oxygen species (ROS), and by improving antioxidant enzyme defenses and crosstalk between NrF2 and NF-ĸB transcription factors. Male Wistar rats were fed a reference diet (RD), RD+AXT, SRD and SRD+AXT [AXT daily oral dose: (10 mg/kg body weight)] for 90 days. Systolic and diastolic blood pressure, biochemical assays in serum and urine were evaluated. Renal cortex samples were taken for histological analysis, determination of triglyceride content, ROS, thiobarbituric acid reactive substances (TBARS), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) enzyme activities and glutathione content (GSH). 4-HNE, NrF2, and NF-ĸB p65 expression were analyzed by immunohistochemistry. We demonstrated that daily oral supplementation of AXT to animals fed a SRD reduced systolic and diastolic blood pressure, histological renal damage, lipid accumulation, ROS and lipid peroxidation, and increased CAT and GPx activities. NrF2 protein expression in renal cortex was increased, whilst NF-ĸB p65 was reduced. AXT extracted from freshwater crabs (Dilocarcinus pagei) may be promising nutritional strategy for the prevention of renal alterations present in this model.

Effects of Full-Spectrum Cannabis Oil with a Cannabidiol:Tetrahydrocannabinol 2:1 Ratio on the Mechanisms Involved in Hepatic Steatosis and Oxidative Stress in Rats Fed a Sucrose-Rich Diet.

Introduction: This study aimed to analyze the effects of cannabis oil (cannabidiol:tetrahydrocannabinol [CBD:THC], 2:1 ratio) on the mechanisms involved in hepatic steatosis and oxidative stress in an experimental model of metabolic syndrome (MS) induced by a sucrose-rich diet (SRD). We hypothesized that noninvasive oral cannabis oil administration improves hepatic steatosis through a lower activity of lipogenic enzymes and an increase in carnitine palmitoyltransferase-1 (CPT-1) enzyme activity involved in the mitochondrial oxidation of fatty acids. Furthermore, cannabis oil ameliorates liver oxidative stress through the regulation of the main regulatory factors involved, nuclear factor erythroid 2 (NrF2) and nuclear factor-kB (NF-κB) p65. For testing this hypothesize, a relevant experimental model of MS was induced by feeding rats with a SRD for 3 weeks. Methods: Male Wistar rats were fed the following diets for 3 weeks: reference diet: standard commercial laboratory diet, SRD, and SRD + cannabis oil: noninvasive oral administration of 1 mg/kg body weight cannabis oil daily. The full-spectrum cannabis oil presents a total cannabinoid CBD:THC 2:1 ratio. Serum glucose, triglyceride, total cholesterol, HDL-cholesterol, LDL-cholesterol, uric acid, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase (AP), N-arachidonoylethanolamine or anandamide and 2-arachidonoylglycerol endocannabinoids levels, thiobarbituric acid reactive substance (TBARS) levels, and non-enzymatic antioxidant capacity (ferric ion-reducing antioxidant power [FRAP]) were evaluated. In the liver tissue: histology, nonalcoholic fatty liver disease activity score (NAS), triglycerides and cholesterol content, lipogenic enzyme activities (fatty acid synthase, acetyl-CoA carboxylase, malic enzyme, and glucose-6-phosphate dehydrogenase), enzyme related to mitochondrial fatty acid oxidation (CPT-1), reactive oxygen species, TBARS, FRAP, glutathione, catalase, glutathione peroxidase, and glutathione reductase enzyme activities. 4-hydroxynonenal, NrF2, and NF-κB p65 levels were analyzed by immunohistochemistry. Results: The results showed that SRD-fed rats developed dyslipidemia, liver damage, hepatic steatosis (increase of key enzymes related to the novo fatty acid synthesis and decrease of key enzyme related to mitochondrial fatty acid oxidation), lipid peroxidation, and oxidative stress. Hepatic NrF2 expression was significantly decreased and NF-κB p65 expression was increased. Cannabis oil administration improved dyslipidemia, liver damage, hepatic steatosis, lipid peroxidation (improving enzymes involved in lipid metabolism), and oxidative stress. In the liver tissue, NrF2 expression increased, and NF-κB p65 expression was reduced. Conclusion: The present study revealed new aspects of liver damage and steatosis, lipid peroxidation, and oxidative stress in dyslipidemic insulin-resistant SRD-fed rats. We demonstrated new properties and molecular mechanisms of cannabis oil (CBD:THC, 2:1 ratio) on lipotoxicity and hepatic oxidative stress in an experimental model of MS.

Salvia hispanica L. (chia) seed promotes body fat depletion and modulates adipocyte lipid handling in sucrose-rich diet-fed rats.

The aim of this study was to analyze the effects of Salvia hispanica L. (chia) seed upon metabolic pathways that play a key role in adipose tissue lipid handling which could be involved in visceral adiposity reduction developed in rats fed a sucrose-rich diet (SRD). Male Wistar rats were fed with a reference diet (RD) -6 months- or SRD-3 months. Then, the last group was randomly divided into two subgroups. One subgroup continued receiving the SRD up to 6 months and the other was fed with a SRD where whole chia seed was incorporated as the source of dietary fat for the next 3 months (SRD + CHIA). Results showed that chia seed in the SRD-fed rat reduced the abdominal and thoracic circumferences, carcass fat content, adipose tissue weights, and visceral adiposity index. This was accompanied by an improvement in insulin sensitivity and plasma lipid profile. In epididymal adipose tissue, the decreased fat cell triglyceride content was associated with a reduction in both, FAT/CD 36 plasma membrane levels and the fat synthesis enzyme activities. There were not changes in oxidative CPT enzyme activities. PKCß and the precursor and mature forms of SREBP-1 protein levels were decreased, while pAMPK was increased. Our findings suggest that chia seed supplementation can modulate essential pathways of lipid metabolism in adipose tissue, contributing to reduced visceral fat accumulation in SRD-fed rats.

Efectos del tratamiento antioxidante en la activación del eje hipotálamo-hipófiso-adrenal inducida por el consumo de dietas ricas en sacarosa / Effects of antioxidant treatment on the activation of the hipotalamo-hipofiso-adrenal axis induced by the consumption of sucrose rich diets

Introducción: dados los efectos pleiotrópicos de los glucocorticoides (GCs) sobre el metabolismo, los niveles excesivos y sostenidos de GCs circulantes tienen efectos deletéreos e incrementan la morbilidad y mortalidad cardiovascular. Objetivos: estudiar el efecto de la terapia antioxidante (con ácido lipoico o melatonina) sobre la hiperactivación del eje hipotálamo-hipófiso-adrenal (HHA) en animales alimentados con dieta rica en sacarosa (DRS). Materiales y métodos: se evaluó la actividad del eje HHA y se determinaron parámetros hormonales, de estrés oxidativo y de inflamación en la adenohipófisis de animales tratados con DRS durante tres semanas. Resultados: los animales del grupo DRS mostraron mayores niveles circulantes de hormona adrenocorticotropa (ACTH, por sus siglas en inglés) y corticosterona. En paralelo se detectó un aumento en la expresión del polipéptido precursor (proopiomelanocortina, POMC) y de ACTH en la adenohipófisis, donde también se observó un aumento de lipoperóxidos y proteínas nitradas en tirosina (daño oxidativo), un mayor número de macrófagos tisulares y un incremento en la producción de IL-1beta. El tratamiento antioxidante previno los cambios en estos parámetros. En particular la melatonina también normalizó la actividad del eje HHA y la expresión hipofisaria de POMC. Conclusiones: la sobrecarga metabólica inducida por la administración de DRS genera daño oxidativo e inflamación en la adenohipófisis. La activación de los macrófagos tisulares producida en consecuencia podría impactar sobre los corticotropos hipofisarios e inducir su hiperfunción. La melatonina podría utilizarse como herramienta terapéutica para normalizar la actividad del eje HHA en modelos de obesidad por dieta.

Introduction: given the pleiotropic effects of glucocorticoids (GCs) on metabolism, excessive and sustained levels of circulating GCs, have deleterious effects and increase cardiovascular morbidity and mortality. Objectives: to study the effect of antioxidant therapy on hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis in animals fed a sucrose-rich diet (SRD). Materials and methods: the activity of the HPA axis was evaluated and hormonal, oxidative stress and inflammation parameters were determined in the adenohypophysis of animals treated with SRD for trhee weeks. Results: animals from the SRD group showed higher circulating levels of adrenocorticotropic hormone (ACTH) and corticosterone. In parallel, an increase in the expression of the polypeptide precursors, POMC and ACTH were detected in the adenohypophysis. We also observed an increase in lipoperoxides and proteins nitrated in tyrosine (oxidative damage), a greater number of tissue macrophages and an increase in the production of IL-1beta. Antioxidant treatment prevented all these changes. In particular, melatonin also normalized the activity of the HPA axis and pituitary expression of POMC. Conclusions: the metabolic overload induced by the administration of SRD generates oxidative damage and inflammation in the adenohypophysis. Activation of tissue macrophages could affect, in turn, pituitary corticotrophs inducing their activation. Melatonin could be used as a therapeutic tool to normalize the activity of the HPA axis in diet obesity models.

Dietary Salvia hispanica L. reduces cardiac oxidative stress of dyslipidemic insulin-resistant rats.

Salvia hispanica L., commonly known as chia seed, has beneficial effects upon some signs of metabolic syndrome (MS), such as dyslipidemia and insulin resistance. However, its action on cardiac oxidative stress associated with MS remains unknown. The goal of this study was to analyze the possible beneficial effects of chia seed (variety Salba) upon the oxidative stress of left ventricle heart muscle (LV) of a well-established dyslipidemic insulin-resistant rat model induced by feeding them a sucrose-rich diet (SRD). Male Wistar rats received an SRD for 3 months. After that, for 3 additional months, half of the animals continued with the SRD, while the other half received the SRD containing chia as the source of dietary fat instead corn oil (SRD+chia). In the LV of SRD-fed rats, chia seed improved/reverted the depleted activity of antioxidant enzymes glutathione peroxidase, superoxide dismutase (SOD), and catalase, and ameliorated manganese superoxide dismutase messenger RNA (mRNA) levels increasing the expression of the nuclear factor erythroid 2-related factor 2 (Nrf2). Improved the glutathione redox estate, reactive oxygen species, and thiobarbituric acid reactive substances contents normalizing the p47NOX subunit mRNA level. Furthermore, chia normalized hypertension and plasma levels of pro-inflammatory cytokines and oxidative stress biomarkers. The findings show that chia seed intake impacts positively upon oxidative imbalance of LV of dyslipidemic insulin-resistant rats. Novelty Healthy effects of chia seed involve an improvement of cardiac antioxidant defenses through Nrf2 induction. Chia seed intake reduces cardiac oxidative stress markers of dyslipidemic insulin-resistant rats. Dietary chia seed restores cardiac unbalanced redox state of dyslipidemic insulin-resistant rats.

Cacao extract enriched in polyphenols prevents endocrine-metabolic disturbances in a rat model of prediabetes triggered by a sucrose rich diet.

ETHNOPHARMACOLOGICAL RELEVANCE: Cocoa extracts rich in polyphenols are used as potential agent for treating diabetes. Cocoa polyphenols have been proved to ameliorate important hallmarks of type-2 diabetes (T2D). They can regulate glucose levels by increasing insulin secretion, promoting ß-cell proliferation and a reduction of insulin resistance. In addition, epidemiological evidence indicates that consumption of flavonoid decreases the incidence of T2D. AIM OF THE STUDY: T2D is preceded by a prediabetic state in which the endocrine-metabolic changes described in T2D are already present. Since epidemiological evidence indicates that consumption of flavonoid decreases its incidence, we evaluated possible preventive effects of polyphenol-enriched cocoa extract on a model of prediabetes induced by sucrose. MATERIALS AND METHODS: We determined circulating parameters and insulin sensitivity indexes, liver protein carbonyl groups and reduced glutathione, liver mRNA expression levels of lipogenic enzymes, expression of different pro-inflammatory mediators, fructokinase activity and liver glycogen content. For that, radioimmunoassay, real-time polymerase chain reaction, Western blot, spectrophotometry, and immunohistochemistry were used. RESULTS: We demonstrated that sucrose administration triggered hypertriglyceridemia, insulin-resistance, and liver increased oxidative stress and inflammation markers compared to control rats. Additionally, we found an increase in glycogen deposit, fructokinase activity, and lipogenic genes expression (SREBP-1c, FAS and GPAT) together with a decrease in P-Akt and P-eNOS protein content (P < 0.05). Sucrose-induced insulin resistance, hepatic carbohydrate and lipid dysmetabolism, oxidative stress, and inflammation were effectively disrupted by polyphenol-enriched cocoa extract (PECE) co-administration (P < 0.05). CONCLUSION: Dietary administration of cocoa flavanols may be an effective and complementary tool for preventing or reverting T2D at an early stage of its development (prediabetes).

Melatonin prevents early pituitary dysfunction induced by sucrose-rich diets.

While physiological levels of glucocorticoids are required to ensure proper functions of the body, consistently high levels may engender several deleterious consequences. We have previously shown an increase in the activity of the hypothalamic-pituitary-adrenal (HPA) axis in rats fed sucrose-rich diets (SRD). The main goal of this study was to analyze the processes involved in the modulation of the pituitary production of ACTH by SRD, and to test melatonin as a possible therapeutic agent for the prevention of the HPA axis dysfunction. Male Wistar rats were fed standard chow and either SRD (30% sucrose in the drinking water) or plain water for three weeks. Melatonin was administered as subcutaneous pellets. Results showed that SRD treatment induced an increase in systemic ACTH and corticosterone levels and a decrease in melatonin levels. In the pituitary gland, we also detected an increase in the expression levels of proopiomelanocortin (POMC) that was accompanied by increased levels of: lipoperoxides, nitro-tyrosine modified proteins, catalase, heme oxygenase-1, interleukin-1ß mRNA, and by an increase in the tissue number of inflammatory cells (F4/80 and Iba-1 positive cells). Melatonin treatment prevented all these systemic and pituitary changes as well as the increase in POMC expression induced by incubation of AtT-20 corticotrophs with conditioned media obtained from stimulated macrophages. In conclusion, stimulation of POMC/ACTH production in rats fed a SRD could involve the generation of oxidative stress and inflammation in the pituitary gland. Melatonin treatment prevented these effects and normalized the activity of the HPA axis.

Dietary soya protein improves intra-myocardial lipid deposition and altered glucose metabolism in a hypertensive, dyslipidaemic, insulin-resistant rat model.

This study investigates the effects of replacing dietary casein by soya protein on the underlying mechanisms involved in the impaired metabolic fate of glucose and lipid metabolisms in the heart of dyslipidaemic rats chronically fed (8 months) a sucrose-rich (62·5 %) diet (SRD). To test this hypothesis, Wistar rats were fed an SRD for 4 months. From months 4 to 8, half the animals continued with the SRD and the other half were fed an SRD in which casein was substituted by soya. The control group received a diet with maize starch as the carbohydrate source. Compared with the SRD-fed group, the following results were obtained. First, soya protein significantly (P<0·001) reduced the plasma NEFA levels and normalised dyslipidaemia and glucose homoeostasis, improving insulin resistance. The protein levels of fatty acid translocase at basal state and under insulin stimulation and the protein levels and activity of muscle-type carnitine palmitoyltransferase 1 were normalised. Second, a significant (P<0·001) reduction of TAG, long-chain acyl CoA and diacylglycerol levels was observed in the heart muscle. Third, soya protein significantly increased (P<0·01) GLUT4 protein level under insulin stimulation and normalised glucose phosphorylation and oxidation. A reduction of phosphorylated AMP protein kinase protein level was recorded without changes in uncoupling protein 2 and PPARα. Fourth, hydroxyproline concentration decreased in the left ventricle and hypertension was normalised. The new information provided shows the beneficial effects of soya protein upon the altered pathways of glucose and lipid metabolism in the heart muscle of this rat model.

Evaluación del efecto hipolipemiante de Talinum triangulare (falsa espinaca) y Abelmoschus esculentus (quimbombó) / Assessment of hypolipidemic action of Talinum triangulare (water leaf) and Abelmoschus esculentus (okra)

Introducción: la evaluación de plantas con efecto reductor en los lípidos plasmáticos, constituye una herramienta muy valiosa para el control de las dislipidemias. Objetivos: comprobar la efectividad farmacológica como hipolipemiante, de Talinum triangulare (Jacq.) Willd (Talinaceae) y Abelmoschus esculentus moench (Malvaceae), en dos biomodelos de ensayo. Métodos: se utilizó el fruto verde de A. esculentus y hojas frescas de Talinum triangulare. El material vegetal previo secado, se pulverizó para preparar extractos hidroalcohólicos, que una vez rotoevaporados, fueron suspendidos en agua para ser administrados a los modelos experimentales. El efecto hipolipémico de las plantas estudiadas se comprobó, en animales de experimentación, sometidos a dos modelos de inducción de hiperlipidemia; administración de solución de sacarosa al 63 por ciento durante 16 semanas y administración vía intraperitoneal del detergente no iónico Poloxamer 338, durante 48 horas a una dosis de 0,6 g/kg. Resultados: el extracto hidroalcohólico de A. esculentus (400 mg/kg) en el modelo de hiperlipemia por Dieta Rica en Sacarosa, mostró un efecto reductor de triacilglicéridos, superior al ácido nicotínico. En el modelo de hiperlipidemia por inducción con detergente no iónico, el extracto hidroalcohólico de Talinum triangulare (400 mg/kg), manifestó un efecto reductor de colesterol y triacilglicéridos, mayor que el ácido nicotínico y la atorvastatina. Conclusiones: los extracto hidroalcohólicos de A. esculentus y de Talinum triangulare expresaron efectos reductores de triacilglicérios por mecanismos de acción diferentes, superiores al ácido nicotínico en cada caso. El extracto hidroalcohólico de Talinum triangulare manifestó un potente efecto reductor de colesterol mayor que el ácido nicotínico y la atorvastatina(AU)

Introduction: assessment of plants with low plasmatic lipids effect is a power instrument to dislipidemias control. Objectives: to establish the pharmacological effectiveness as hipolipidemic agents of Talinum triangulare (Jacq.) Willd (Portulacaceae) and Abelmoschus esculentus Moench (Malvaceae) in two biomodel assays. Methods: in the present study we have researched the hypolipemic effect of Talinum triangulare (false spinach) and A. esculentus (okra) in experimental animals subjected to two models of hyperlipidemia induction; an intake of 63 percent sucrose solution for 16 weeks and an intake of Poloxamer 338 nonionic detergent via intraperitoneal for 48 hours at a dose of 0,6 g/kg. Results: the hydroalcoholic extract of A. esculentus, at a dose of 400 mg/kg showed triacilglicéridos reducing effect greater than nicotinic acid in the model of hyperlipidemia induction by a sucrose-rich diet. In the model of hyperlipidemia by induction with nonionic detergent, the hydroalcoholic extract of Talinum triangulare at a dose of 400 mg/kg, showed a powerful cholesterol and triacilglicéridos lowering effect, greater than nicotinic acid and atorvastatin. Conclusions: the hydroalcoholic extract of A. esculentus and T. triangulare showed hypotriglyceridemic effect for different action mechanisms, higher than the nicotinic acid, in each case. The extract hidroalcohólico of Talinum triangulare showed a potent hipocholesterolemic effect even more than the nicotinic acid and the atorvastatin(AU)

Evaluación del efecto hipolipemiante de Talinum triangulare (falsa espinaca) y Abelmoschus esculentus (quimbombó) / Assessment of hypolipidemic action of Talinum triangulare (water leaf) and Abelmoschus esculentus (okra)

INTRODUCCIÓN: la evaluación de plantas con efecto reductor en los lípidos plasmáticos, constituye una herramienta muy valiosa para el control de las dislipidemias. OBJETIVOS: comprobar la efectividad farmacológica como hipolipemiante, de Talinum triangulare (Jacq.) Willd(Talinaceae) y Abelmoschus esculentus moench (Malvaceae), en dos biomodelos de ensayo. MÉTODOS: se utilizó el fruto verde de A. esculentus y hojas frescas de Talinum triangulare. El material vegetal previo secado, se pulverizó para preparar extractos hidroalcohólicos, que una vez rotoevaporados, fueron suspendidos en agua para ser administrados a los modelos experimentales. El efecto hipolipémico de las plantas estudiadas se comprobó, en animales de experimentación, sometidos a dos modelos de inducción de hiperlipidemia; administración de solución de sacarosa al 63 % durante 16 semanas y administración vía intraperitoneal del detergente no iónico Poloxamer 338, durante 48 horas a una dosis de 0,6 g/kg. RESULTADOS: el extracto hidroalcohólico de A. esculentus (400 mg/kg) en el modelo de hiperlipemia por Dieta Rica en Sacarosa, mostró un efecto reductor de triacilglicéridos, superior al ácido nicotínico. En el modelo de hiperlipidemia por inducción con detergente no iónico, el extracto hidroalcohólico de Talinum triangulare (400 mg/kg), manifestó un efecto reductor de colesterol y triacilglicéridos, mayor que el ácido nicotínico y la atorvastatina. CONCLUSIONES: los extracto hidroalcohólicos de A. esculentus y de Talinum triangulare expresaron efectos reductores de triacilglicérios por mecanismos de acción diferentes, superiores al ácido nicotínico en cada caso. El extracto hidroalcohólico de Talinum triangulare manifestó un potente efecto reductor de colesterol mayor que el ácido nicotínico y la atorvastatina.

INTRODUCTION: assessment of plants with low plasmatic lipids effect is a power instrument to dislipidemias control. OBJECTIVES: to establish the pharmacological effectiveness as hipolipidemic agents of Talinum triangulare (Jacq.) Willd (Portulacaceae) and Abelmoschus esculentus Moench (Malvaceae) in two biomodel assays. METHODS: in the present study we have researched the hypolipemic effect of Talinum triangulare (false spinach) and A. esculentus (okra) in experimental animals subjected to two models of hyperlipidemia induction; an intake of 63 % sucrose solution for 16 weeks and an intake of Poloxamer 338 nonionic detergent via intraperitoneal for 48 hours at a dose of 0,6 g/kg. RESULTS: the hydroalcoholic extract of A. esculentus, at a dose of 400 mg/kg showed triacilglicéridos reducing effect greater than nicotinic acid in the model of hyperlipidemia induction by a sucrose-rich diet. In the model of hyperlipidemia by induction with nonionic detergent, the hydroalcoholic extract of Talinum triangulare at a dose of 400 mg/kg, showed a powerful cholesterol and triacilglicéridos lowering effect, greater than nicotinic acid and atorvastatin. CONCLUSIONS: the hydroalcoholic extract of A. esculentus and T. triangulare showed hypotriglyceridemic effect for different action mechanisms, higher than the nicotinic acid, in each case. The extract hidroalcohólico of Talinum triangulare showed a potent hipocholesterolemic effect even more than the nicotinic acid and the atorvastatin.