RESUMO
An imbalance in the redox state, increased levels of lipid precursors and overactivation of de novo lipogenesis determine the development of fibrosis during nonalcoholic steatohepatitis (NASH). We evaluated the modulation of NADPH-producing enzymes associated with the antifibrotic, antioxidant and antilipemic effects of nicotinamide (NAM) in a model of NASH induced by excess fructose consumption. Male rats were provided drinking water containing 40% fructose for 16 weeks. During the last 12 weeks of fructose administration, water containing NAM was provided to some of the rats for 5 h/day. The biochemical profiles and the ghrelin, leptin, lipoperoxidation and TNF-α levels in serum and the glucose-6-phosphate dehydrogenase (G6PD), malic enzyme (ME) and NADP+-dependent isocitric dehydrogenase (IDP) levels, the reduced/oxidized glutathione (GSH/GSSG) and reduced/oxidized nicotinamide adenine dinucleotide (phosphate) (NAD(P)H/NAD(P)+) ratios, and the levels of various lipogenic and fibrotic markers in the liver were evaluated. The results showed that hepatic fibrosis induced by fructose consumption was associated with weight gain, hunger-satiety system dysregulation, hyperinsulinemia, dyslipidemia, lipoperoxidation and inflammation. Moreover, increased levels of hepatic G6PD and ME activity and expression, the NAD(P)H/NAD(P)+ ratios, and GSSG concentration and increased expression of lipogenic and fibrotic markers were detected, and these alterations were attenuated by NAM administration. Specifically, NAM diminished the activity and expression of G6PD and ME, and this effect was associated with a decrease in the NADPH/NADP+ ratios, increased GSH levels and decreased lipoperoxidation and inflammation, ameliorating fibrosis and NASH development. NAM reduces liver steatosis and fibrosis by regulating redox homeostasis through a G6PD- and ME-dependent mechanism.
Assuntos
Fígado Gorduroso/metabolismo , Fígado Gorduroso/prevenção & controle , Niacinamida/farmacologia , Animais , Antioxidantes/metabolismo , Frutose/efeitos adversos , Frutose/metabolismo , Glucose/metabolismo , Glutationa/metabolismo , Homeostase , Metabolismo dos Lipídeos/fisiologia , Lipídeos/biossíntese , Lipogênese/fisiologia , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/patologia , Masculino , NAD/metabolismo , NADP/metabolismo , Niacinamida/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Oxirredução/efeitos dos fármacos , Ratos , Ratos Sprague-DawleyRESUMO
Type 2 diabetes is characterized by oxidative stress and a chronic low-grade inflammatory state, which also play roles in the pathogenesis of this disease and the accompanying vascular complications by increasing the production of free radicals and pro-inflammatory cytokines. Cucurbita ficifolia Bouché (C. ficifolia) is an edible Mexican plant whose hypoglycemic activity has been demonstrated in several experimental and clinical conditions. Recently, D-chiro-inositol has been proposed as the compound responsible for the hypoglycemic effects; however, the antioxidant and anti-inflammatory potential of this plant has not yet been explored. The aim of this research is to study the influence of a hypoglycemic, D-chiro-inositol-containing fraction from the C. ficifolia fruit (AP-Fraction) on biomarkers of oxidative stress, as well as on the inflammatory cytokines in streptozotocin-induced diabetes. The AP-Fraction obtained from the mature fruit of C. ficifolia contained 3.31 mg of D-chiro-inositol/g of AP-Fraction. The AP-Fraction was administrated daily by gavage to normal mice for 15 days as a preventive treatment. Then these animals were given streptozotocin, and the treatments were continued for an additional 33 days. Pioglitazone was used as a hypoglycemic drug for comparison. Administration of the AP-Fraction significantly increased glutathione (GSH) and decreased malondialdehyde (MDA) in the liver without significantly affecting the levels in other tissues. The AP-Fraction reduced TNF-α and increased IL-6 and IFN-γ in serum. Interestingly, the AP-Fraction also increased IL-10, an anti-inflammatory cytokine. These results suggest that C. ficifolia might be used as an alternative medication for the control of diabetes mellitus and that it has antioxidant and anti-inflammatory properties in addition to its hypoglycemic activity.
Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Cucurbita/química , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Inositol/uso terapêutico , Fitoterapia , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Glicemia/metabolismo , Citocinas/sangue , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2 , Frutas , Glutationa/metabolismo , Hipoglicemiantes/farmacologia , Mediadores da Inflamação/sangue , Inositol/farmacologia , Fígado/metabolismo , Masculino , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos , Estresse Oxidativo/efeitos dos fármacos , Pioglitazona , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Tiazolidinedionas/farmacologiaRESUMO
ETHNOPHARMACOLOGICAL IMPORTANCE: Psacalium peltatum (H.B.K.) Cass. (Asteraceae) is used medicinally to treat diabetes, rheumatic pains, as well as gastrointestinal and kidney ailments. Previous pharmacological and chemical assays have demonstrated that an aqueous fraction from Psacalium peltatum (AP-fraction) contains a carbohydrate-type compound with hypoglycemic activity. Nevertheless, studies have not yet considered the hypoglycemic action of the AP-faction by sub-chronic administration nor on other healing properties, some of which might be associated with DM2 and other inflammatory processes. AIM OF STUDY: To determine whether a hypoglycemic carbohydrate fraction (AP-fraction) from Psacalium peltatum roots has antioxidant and anti-inflammatory effects in streptozotocin-induced diabetes mice. MATERIAL AND METHODS: Healthy mice received either saline, the AP-fraction with a high content of fructans, or pioglitazone (a positive control) daily by gavage. After 15 days of treatment, these animals received a single intraperitoneal administration of streptozotocin and all treatments were continued for additional 33 days. The antioxidant and anti-inflammatory properties of the AP-fraction were evaluated through the quantification of biomarkers of oxidative stress (glutathione (GSH) and malondialdehyde (MDA)) and inflammation (interleukin (IL)-6, tumor necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ), and IL-10). RESULTS: The AP-fraction reduced glycemia and the glycated hemoglobin. Furthermore, animals treated with the AP-fraction had increased GSH, while MDA was decreased in the liver and the heart, without changes in the kidneys and the pancreas. The AP-fraction significantly reduced TNF-α serum levels but did not modify IL-6; in addition, this fraction increased IFN-γ and IL-10 levels. The increase in IL-10 levels may indicate an inhibition of the production of pro-inflammatory cytokines such as TNF-α, whereas the increase in IFN-γ might be indicative of a beneficial effect on the immune system. CONCLUSIONS: The AP-fraction hypoglycemic fructans from Psacalium peltatum roots showed antioxidant and anti-inflammatory properties in mice with streptozotocin-induced diabetes. The Psacalium peltatum hypoglycemic fructans may be valuable in preventing insulin resistance, as well as the development and progression of diabetic complications caused by chronic inflammation.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Antioxidantes/farmacologia , Asteraceae/química , Diabetes Mellitus Experimental/tratamento farmacológico , Frutanos/farmacologia , Hipoglicemiantes/farmacologia , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios não Esteroides/análise , Glicemia/metabolismo , Diabetes Mellitus Experimental/metabolismo , Interferon gama/metabolismo , Interleucina-10/análise , Interleucina-10/metabolismo , Interleucina-6/análise , Interleucina-6/metabolismo , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/química , Raízes de Plantas/química , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Killer cell immunoglobulin-like receptors are characterized by their great diversity of genes and alleles. Population studies have identified the presence of a broad variety of genotypes. In Mexico, there are diverse ethnic groups representing 9% of the total population and the rest is composed of Mestizos with a more varied biology. For the purpose of this study, genotyping was performed in Mestizos, in Mexico City inhabitants, and in three ethnic groups. The frequencies of genes KIR2DL2, 2DL5, 2DS1-3, 2DS5, and 3DS1 showed a greater variability in the groups studied. A total of 12 different genotypes were identified, the higher number for the Mestizos and the lower number for the Tarahumaras. Genotype 1 was found at a greater frequency in all the groups, except for the Tarahumaras, in which genotype 4 was more frequent. The frequency of genotypes 4 and 8 in Mexicans was higher than that for other populations analyzed. By subtyping of KIR3DL1, 3DL2, 2DL1, and 2DL3, two B haplotypes were identified in families; both were absent in Caucasian families. Our results indicated a greater diversity of genes in the Mestizos group than in the ethnic groups.
Assuntos
Indígena Americano ou Nativo do Alasca/genética , Etnicidade/genética , Receptores Imunológicos/genética , Frequência do Gene , Variação Genética , Genótipo , Haplótipos , Humanos , Desequilíbrio de Ligação , México/etnologia , População/genética , Receptores KIR , Receptores KIR2DL1 , Receptores KIR2DL2 , Receptores KIR2DL3 , Receptores KIR3DL1 , Receptores KIR3DL2 , Receptores KIR3DS1RESUMO
Glucose auto-oxidation may be a significant source of reactive oxygen species (ROS), and also be important in the lipid peroxidation process, accompanied by the release of toxic reactive products. We wanted to demonstrate that acrolein can be formed directly and actively from free fatty acids in a hyperglycemic environment. A suspension of linoleic and arachidonic acids (2.5 mM) was exposed to different glucose concentrations (5, 10 and 15 mmol/L) in vitro. The samples were extracted with organic solvents, partitioned, followed at 255-267 nm, and analysed using capillary electrophoresis and mass spectroscopy. The total release of aldehydes significantly (P < 0.01) increased from 1.0 to 5.1, 8.3 and 13.1 micromol/L after 6 hours of incubation, proportional to glucose concentrations. It was possible to verify a correlate hydroperoxide formation as well. Among the lipid peroxidation products, acrolein (5% of total) and its condensing product, 4-hydroxy-hexenal, were identified. From the results presented here, it was possible to demonstrate the production of acrolein, probably as a fatty acid product, due to free radicals generated from the glucose auto-oxidation process. The results led us to propose that acrolein, which is one of the most toxic aldehydes, is produced during hyperglycemic states, and may lead to tissue injury, as one of the initial problems to be linked to high levels of glucose in vivo.
Assuntos
Acroleína/metabolismo , Ácidos Graxos Insaturados/metabolismo , Glucose/farmacologia , Peroxidação de LipídeosRESUMO
Ovulation is a complex process involving not only gonadotropins and steroid hormones, but also many local mediators common to inflammatory reactions, such as cytokines. Of particular interest is the ovarian interleukin-1 (IL-1) system, which may be an intermediary of gonadotropins in the ovulatory process. The preovulatory follicles have a complete and highly compartmentalized intraovarian IL-1 system including ligands, receptor, and receptor antagonist. IL-1 has been considered as the inductor of several ovulation-associated events such as prostaglandin and progesterone biosynthesis, plasminogen activator production, glycosaminoglycan generation, and enhancement of vascular permeability. The principal effector of the IL-1 system is nitric oxide. This paper analyzes the sites of synthesis and action of the IL-1 system in preovulatory follicle and its vascular dynamics as well as IL-1's mechanism of action in triggering follicular rupture.
Assuntos
Interleucina-1/fisiologia , Óxido Nítrico/fisiologia , Ovulação/fisiologia , Feminino , Fase Folicular/fisiologia , Humanos , Folículo Ovariano/fisiologia , Progesterona/fisiologia , Prostaglandinas/fisiologia , Testosterona/fisiologiaRESUMO
Cell death can occur through apoptotic or necrotic death pathways. Membrane disruption leads to inflammation, a typical feature of necrosis. Apoptosis constitutes a genetically controlled physiologic process of cell removal. It is characterized by cell shrinkage, chromatin condensation, and DNA cleavage. Apoptotic cells are rapidly recognized and engulfed by phagocytes thus inhibiting an inflammatory response following necrosis. Apoptosis has been proposed as a basic event to protect tissue homeostasis. This paper analyzes the genetic, biochemical, and morphologic characteristics related to apoptosis, as well as its relationship to certain illnesses.
Assuntos
Apoptose , Apoptose/genética , Doença , HumanosRESUMO
Cytokines synthesized by the uterus or placenta include those thought to be produced exclusively by, or though to act on, cells of the lymphohematopoietic system. Although many of these cytokines are protein mediators of the immune system effector phase, in the female reproductive tract their principal target cells and sites of synthesis are non-lymphohematopoietic cells. During pregnancy, uterine epithelial cells, decidual cells and trophoblast appear to be major sources of the classic lymphohematopoietic cytokines. This suggests two not necessarily exclusive alternatives: that these cells are extensions of, or are involved in, regulating the immune system, or that these factors regulate growth and differentiation of uterine and embryonic tissues. This paper analyzes the sites of synthesis, targets and possible functions of the cytokines during early pregnancy.
Assuntos
Citocinas/fisiologia , Endométrio/fisiologia , Gravidez/fisiologia , Animais , Blastocisto/fisiologia , Fatores Estimuladores de Colônias/fisiologia , Decídua/fisiologia , Desenvolvimento Embrionário , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/fisiologia , Humanos , Interleucinas/fisiologia , Camundongos , Ratos , Fator de Crescimento Transformador beta/fisiologia , Fator de Necrose Tumoral alfa/fisiologia , Útero/fisiologiaRESUMO
OBJECTIVE: To test the Szego hypothesis of increased beta-glucuronidase and acid phosphatase activities in hormone target tissues. METHODS: The presence of beta-glucuronidase and acid phosphatase activities in nuclear subcellular fractions obtained from decidual (implantation site) and stromal (nonimplantation zone) tissues was demonstrated by both biochemical measurements and ultramicrographic analysis utilizing a histochemical reaction. RESULTS: Acid phosphatase was almost twice as abundant in nuclei and lysosomes of epithelial cells (implantation sites), and beta-glucuronidase also was significantly more active in nuclei from epithelial and decidual tissues than in nonimplantation tissue. CONCLUSION: Our results, utilizing the implantation process as experimental model, support the Szego hypothesis of the lysosomal role in hormonal mechanisms of action.