Joel Ramírez-Emiliano

A PPARγ, NF-κB and AMPK-Dependent Mechanism May Be Involved in the Beneficial Effects of Curcumin in the Diabetic db/db Mice Liver

Turmeric (Curcuma longa) is a rhizomatous herbaceous perennial plant of the ginger family which has been used to treat biliary disorders, anorexia, cough, rheumatism, cancer, sinusitis, hepatic disorders, hyperglycemia, obesity, and diabetes in both Ayurvedic and Traditional Chinese Medicine. Suggested mechanisms of action include the modulation of signal transduction cascades and effects on gene expression, however they remain to be elucidated. In this study, the expression of some proteins responsible for transcription factors, inflammation, and metabolic control were evaluated by western blot in 15-week-old db/db mice livers treated with curcumin 0.75% mixed in their diet for 8 weeks. In addition, nitrosative stress was evaluated. Curcumin increased the expression of AMPK and PPARγ, and diminished NF-κB protein in db/db mice. However, it did not modify the expression of PGC-1α or SIRT1. Nitrosative stress present in db/db mice livers was determined by a unique nitrotyrosylated protein band (75 kDa) and was not reverted with curcumin. In conclusion, curcumin regulates the expression of AMPK, PPARγ, and NF-κB; suggesting a beneficial effect for treatment of T2DM complications. In order to observe best beneficial effects it is desirable to administer curcumin in the earlier states of T2DM.

Expression of Inducible Nitric Oxide Synthase mRNA and Nitric Oxide Production During the Development of Liver Abscess in Hamster Inoculated with Entamoeba histolytica

The present study analyzed iNOS and eNOS mRNA expression and NO production during development of hepatic abscess caused by Entamoeba histolytica trophozoites. One 374-bp sequence, which displayed 88% identity to mammalian iNOS protein, was isolated from LPS-stimulated peritoneal hamster macrophages. A separate 365-bp cDNA sequence showed 99% identity with eNOS protein. iNOS mRNA was detected in hamsters during formation of amoebic liver abscesses, but not in control hamsters. eNOS mRNA expression was not modified. Serum nitrite concentration in hamsters infected with E. histolytica was 33 ± 6 μM, in control hamsters was 20 ± 3 μM. The study shows that iNOS mRNA expression and NO production are induced by E. histolytica trophozoites during amoebic liver abscess formation. However, in spite of iNOS mRNA expression and NO production, E. histolytica trophozoites induced liver abscess formation in hamster.

Selective Protection Against Oxidative Damage in Brain of Mice With a Targeted Disruption of the Neuronal Nitric Oxide Synthase Gene

Nitric oxide (NO) is an essential messenger molecule in brain, where it is produced in neurons mostly by the activity of the neuronal isoform of nitric oxide synthase (nNOS). To understand the participation of the different isoforms of NOS in physiological functioning and in pathological processes, mice with null mutations for each of the NOS isoforms have been generated. In the present paper, we report that there is a selective protection from oxidative damage in the brain of mice with a targeted disruption of the nNOS gene. The cerebellum of these mice shows reduced levels of lipid peroxidation (LP) at the different ages tested, compared with wild‐type mice, and also a reduction in the formation of reactive oxygen species (ROS). We observed a decrease of LP in cortex, and no effect on either LP or ROS formation was observed in striatum of knockout mice compared with wild type. We also report increased spontaneous motor activity of knockout mice. The expression and activity of nNOS are crucial to maintain redox status in brain, and we consider that the alteration in oxidative damage may help us to explain the phenotypical characteristics of nNOS knockout mice and their differential susceptibility to brain insults.

Curcumin restores mitochondrial functions and decreases lipid peroxidation in liver and kidneys of diabetic db/db mice

BackgroundNitrosative and oxidative stress play a key role in obesity and diabetes-related mitochondrial dysfunction. The objective was to investigate the effect of curcumin treatment on state 3 and 4 oxygen consumption, nitric oxide (NO) synthesis, ATPase activity and lipid oxidation in mitochondria isolated from liver and kidneys of diabetic db/db mice.ResultsHyperglycaemia increased oxygen consumption and decreased NO synthesis in liver mitochondria isolated from diabetic mice relative to the control mice. In kidney mitochondria, hyperglycaemia increased state 3 oxygen consumption and thiobarbituric acid-reactive substances (TBARS) levels in diabetic mice relative to control mice. Interestingly, treating db/db mice with curcumin improved or restored these parameters to normal levels; also curcumin increased liver mitochondrial ATPase activity in db/db mice relative to untreated db/db mice.ConclusionsThese findings suggest that hyperglycaemia modifies oxygen consumption rate, NO synthesis and increases TBARS levels in mitochondria from the liver and kidneys of diabetic mice, whereas curcumin may have a protective role against these alterations.

A high-fat diet decreases GABA concentration in the frontal cortex and hippocampus of rats.

BackgroundIt has been proposed that the γ-aminobutyric acid (GABA) plays a key role in the regulation of food intake and body weight by controlling the excitability, plasticity and the synchronization of neuronal activity in the frontal cortex (FC). It has been also proposed that the high-fat diet (HFD) could disturb the metabolism of glutamate and consequently the GABA levels, but the mechanism is not yet clearly understood. Therefore, the aim of this study was to investigate the effect of a HFD on the GABA levels in the FC and hippocampus of rats.ResultsThe HFD significantly increased weight gain and blood glucose levels, whereas decreased the GABA levels in the FC and hippocampus compared with standard diet-fed rats.ConclusionsHFD decreases GABA levels in the FC and hippocampus of rat, which likely disrupts the GABAergic inhibitory processes, underlying feeding behavior.

Agave fructans and oligofructose decrease oxidative stress in brain regions involved in learning and memory of overweight mice

Abstract Obesity is currently a public health problem worldwide. Recently, non-reducing carbohydrates, that include β(2→1) and β(2→6) linkages in their structure, have been of particular interest in the field of obesity because they are involved in lipid metabolism. Some of these are agave fructans (AF) and oligofructose (OF). In this study, we evaluated both AF and OF on oxidative stress (OS) markers in the brain of overweight mice (OM). AF and OF decreased TBARS levels and carbonyls at different levels in hippocampus (HP), frontal cortex (FC) and cerebellum (CB) of OM. The results indicated that fructans may have anti-oxidative potential and can be used as an alternative treatment for the prevention of the consequences of this pathology.

Ultraviolet light-C increases antioxidant capacity of the strawberry (Fragaria x ananassa) in vitro and in high-fat diet-induced obese rats

Abstract Flavonoids and polyphenols from the strawberry and other fruits have been proposed to reduce the oxidative stress produced by the obesity and her complications. Moreover, it has been proposed that irradiation with UV‐C to strawberry may increase the antioxidant capacity of this fruit. The aim of the present study was to explore the effects of the UV‐C on antioxidant capacity of strawberry in vitro and in vivo. Strawberry slices were irradiated with ultraviolet light‐C (UV‐C) at 1.2 W/m2/16.5 min; then, the power antioxidant was isolated from the nonirradiated and irradiated strawberry slices into an organic phase, which was lyophilized to finally producing a nonirradiated strawberry extract (NSE) and UV‐irradiated strawberry extract (UViSE) powder. After the antioxidant capacity of both extracts were determined in vitro using the Trolox equivalent antioxidant capacity (TEAC) assay and in vivo using high‐fat diet‐induced obese rats. Our results demonstrated that irradiation with UV‐C to strawberry slices increased the antioxidants content, which was corroborated in vitro, where the antioxidant capacity of UViSE was higher than the NSE. However, in obese rats, the reduction in the oxidative damage by the UViSE and NSE were similar in peripheral tissues. Interestingly, the UViSE was better than the NSE to reduce the oxidative damage in brain. In conclusion, UV‐irradiation increases the antioxidants content of strawberry that is correlated with an increased antioxidant capacity in vitro, but in rats, this antioxidant capacity may be more effective in brain than in peripheral tissues.

Protein Expression Profile of Twenty-Week-Old Diabetic db/db and Non-Diabetic Mice Livers: A Proteomic and Bioinformatic Analysis

Type 2 diabetes mellitus is characterized by insulin resistance in the liver. Insulin is not only involved in carbohydrate metabolism, it also regulates protein synthesis. This work describes the expression of proteins in the liver of a diabetic mouse and identifies the metabolic pathways involved. Twenty-week-old diabetic db/db mice were hepatectomized, after which proteins were separated by 2D-Polyacrylamide Gel Electrophoresis (2D-PAGE). Spots varying in intensity were analyzed using mass spectrometry, and biological function was assigned by the Database for Annotation, Visualization and Integrated Discovery (DAVID) software. A differential expression of 26 proteins was identified; among these were arginase-1, pyruvate carboxylase, peroxiredoxin-1, regucalcin, and sorbitol dehydrogenase. Bioinformatics analysis indicated that many of these proteins are mitochondrial and participate in metabolic pathways, such as the citrate cycle, the fructose and mannose metabolism, and glycolysis or gluconeogenesis. In addition, these proteins are related to oxidation–reduction reactions and molecular function of vitamin binding and amino acid metabolism. In conclusion, the proteomic profile of the liver of diabetic mouse db/db exhibited mainly alterations in the metabolism of carbohydrates and nitrogen. These differences illustrate the heterogeneity of diabetes in its different stages and under different conditions and highlights the need to improve treatments for this disease.

Mitochondrial content, oxidative, and nitrosative stress in human full-term placentas with gestational diabetes mellitus

BackgroundThe purpose of this study was to determine the mitochondrial content, and the oxidative and nitrosative stress of the placenta in women with gestational diabetes mellitus (GDM).MethodsFull-term placentas from GDM and healthy pregnancies were collected following informed consent. The lipid peroxidation (TBARS) and oxidized protein (carbonyls) levels were determined by spectrophotometry, and 3-nitrotyrosine (3-NT), subunit IV of cytochrome oxidase (COX4), adenosine 5′-monophosphate (AMP)–activated protein kinase (AMPK) and actin were determined by western blot, whereas ATPase activity was performed by determining the adenosine triphosphate (ATP) consumption using a High-performance liquid chromatography (HPLC) system.ResultsTBARS and carbonyls levels were lower in the placentas of women with GDM compared with the normal placentas (p < 0.001 and p < 0.05, respectively). Also, 3-NT/actin and AMPK/actin ratios were higher in GDM placentas than in the normal placentas (p = 0.03 and p = 0.012, respectively). Whereas COX4/actin ratio and ATPase activity were similar between GDM placentas and those controls.ConclusionsThese data suggest that placentas with GDM are more protected against oxidative damage, but are more susceptible to nitrosative damage as compared to normal placentas. Moreover, the increased expression levels of AMPK in GDM placentas suggest that AMPK might have a role in maintaining the mitochondrial biogenesis at normal levels.Trial registrationHGRL28072011. Registered 28 July 2011.

Curcumin increases the expression of PPARγ and decreases TNF-α expression in heart of db/db diabetic mice

La diabetes es una enfermedad metabolica caracterizada por hiperglucemia y resistencia a la insulina. La curcumina, potencial agente antidiabetico, regula la expresion genica y diferentes vias de senalizacion. El objetivo es determinar el efecto de la curcumina sobre la expresion de proliferador peroxisomal gamma (PGC)-1 α , proliferador de peroxisomas gamma (PPAR γ ) y factor de necrosis tumoral alfa (TNF)- α en corazon de raton diabetico db/db. Para ello, se utilizaron tres grupos de ratones ( n = 3): silvestres (WT), diabeticos (db/db) y diabeticos tratados con curcumina (db/db+C). La curcumina (0.75%) se administro en la dieta durante ocho semanas. La expresion de las proteinas se determino por Western blot. Como resultado, la curcumina previno la subita perdida de peso en los ratones db/db, pero no tuvo efecto sobre los niveles de glucosa sanguinea. La curcumina incremento la expresion de PPAR γ y disminuyo la expresion de TNF- α en los ratones diabeticos, pero no modifico la expresion de PGC-1 α . Se concluye que la curcumina regula la expresion de PPAR γ , factor nuclear kappa de los infocitos B (NF- κ B), pero no la de PGC-1 α .