Targeting the Tumor Vascular Supply to Enhance Radiation Therapy Administered in Single or Clinically Relevant Fractionated Schedules.

This pre-clinical study was designed to demonstrate how vascular disrupting agents (VDAs) should be administered, either alone or when combined with radiation in clinically relevant fractionated radiation schedules, for the optimal anti-tumor effect. CDF1 mice, implanted in the right rear foot with a 200 mm3 murine C3H mammary carcinoma, were injected with various doses of the most potent VDA drug, combretastatin A-1 phosphate (CA1P), under different schedules. Tumors were also locally irradiated with single-dose, or stereotactic (3 × 5-20 Gy) or conventional (30 × 2 Gy) fractionation schedules. Tumor growth and control were the endpoints used. Untreated tumors had a tumor growth time (TGT5; time to grow to 5 times the original treatment volume) of around 6 days. This increased with increasing drug doses (5-100 mg/kg). However, with single-drug treatments, the maximum TGT5 was only 10 days, yet this increased to 19 days when injecting the drug on a weekly basis or as three treatments in one week. CA1P enhanced radiation response regardless of the schedule or interval between the VDA and radiation. There was a dose-dependent increase in radiation response when the combined with a single, stereotactic, or conventional fractionated irradiation, but these enhancements plateaued at around a drug dose of 25 mg/kg. This pre-clinical study demonstrated how VDAs should be combined with clinically applicable fractionated radiation schedules for the optimal anti-tumor effect, thus suggesting the necessary pre-clinical testing required to ultimately establish VDAs in clinical practice.

Dietary pterostilbene exerts potential protective effects by regulating lipid metabolism and enhancing antioxidant capacity on liver in broilers.

Intensive breeding of broilers met the increasing demands of human for broiler products, but it raised their increased susceptibility to various stressors resulting in the disorder of lipid metabolism. Pterostilbene, the methoxylated analogue of resveratrol, exhibits astonishing functions of antioxidant, anti-inflammatory and glycolipid regulatory. The study aimed to elucidate the protective effects of pterostilbene on broiler liver and to explore the potential mechanisms. A total of 480 one-day-old male Arbor Acres (AA) broilers were randomly divided into four groups: the control group (basal diet) and pterostilbene groups (PT200, PT400, and PT600 feeding with basal diet containing 200, 400 and 600 mg/kg pterostilbene, respectively). The results showed that the dietary pterostilbene supplementation significantly improved the ADG of broilers. Dietary pterostilbene supplementation regulated the expression levels of the genes Sirt1 and AMPK and the downstream genes related to lipid metabolism to protect liver function and reduce lipid accumulation in broilers. Dietary pterostilbene supplementation upregulated the expression levels of the Nrf2 gene and its downstream antioxidant genes (SOD, CAT, HO-1, NQO-1, GPX) and phase II detoxification enzyme-related genes (GST, GCLM, GCLC). Collectively, pterostilbene was confirmed the positive effects as a feed additive on lipid metabolism and antioxidant via regulating Sirt1/AMPK and Nrf2 signalling pathways in broilers.

In vivo modification of the enamel pellicle and saliva resveratrol levels after use of resveratrol-containing orodispersible capsules.

OBJECTIVES: To evaluate in vivo 1) the bioavailability of trans-resveratrol when administered through sublingual capsules; 2) the effect of resveratrol on the protein composition of the acquired enamel pellicle (AEP). DESIGN: Ten volunteers received a sublingual capsule containing 50 mg of trans-resveratrol. Unstimulated saliva was then collected after 0, 30, 60, and 120 min and AEP was collected after 120 min following administration of the capsule. In the next week, the volunteers received a placebo sublingual capsule, and saliva and AEP were collected again. Saliva samples were analyzed for free trans-resveratrol using high-performance liquid chromatopgraphy (HPLC), and AEP samples were subjected to proteomic analysis (nLC-ESI-MS/MS). RESULTS: Trans-resveratrol was detected in saliva at all the time points evaluated, with the peak at 30 min. A total of 242 proteins were identified in both groups. Ninety-six proteins were increased and 23 proteins were decreased in the Resveratrol group. Among the up-regulated proteins, isoforms of cystatins, PRPs, Mucin-7, Histatin-1, Lactotrasnferrin and Lysozyme-C were increased and the isoforms of Protein S100, Neutrophil defensins, Albumin, PRPs, and, Statherin were decreased in Resveratrol group. CONCLUSION: The sublingual capsule is effective at increasing the bioavailability of trans-resveratrol in saliva. Several proteins involved in important processes to maintain systemic and oral health homeostasis were identified. These proteins differently expressed due to the presence of trans-resveratrol deserve attention for future studies, since they have important functions, mainly related to antimicrobial action.

Engineering resveratrol-loaded chitosan nanoparticles for potential use against Helicobacter pylori infection.

Helicobacter pylori (H. pylori) is a microorganism directly linked to severe clinical conditions affecting the stomach. The virulence factors and its ability to form biofilms increase resistance to conventional antibiotics, growing the need for new substances and strategies for the treatment of H. pylori infection. The trans-resveratrol (RESV), a bioactive polyphenol from natural sources, has a potential activity against this gastric pathogen. Here, Chitosan nanoparticles (NP) containing RESV (RESV-NP) were developed for H. pylori management. The RESV-NP were prepared using the ionic gelation method and characterized by Dynamic Light Scattering (DLS), Nanoparticle Tracking Analysis (NTA) and, Cryogenic Transmission Electron Microscopy (Cryo - TEM). The encapsulation efficiency (EE) and in vitro release rate of RESV were quantified using high-performance liquid chromatography (HPLC). RESV-NP performance against H. pylori was evaluated by the quantification of the minimum inhibitory/bactericidal concentrations (MIC/MBC), time to kill, alterations in H. pylori morphology in its planktonic form, effects against H. pylori biofilm and in an in vitro infection model. RESV-NP cytotoxicity was evaluated against AGS and MKN-74 cell lines and by hemolysis assay. Acute toxicity was tested using Galleria mellonella model assays. RESV-NP showed a spherical shape, size of 145.3 ± 24.7 nm, polydispersity index (PDI) of 0.28 ± 0.008, and zeta potential (ZP) of + 16.9 ± 1.81 mV in DLS, while particle concentration was 3.12 x 1011 NP/mL (NTA). RESV-NP EE was 72 %, with full release within the first 5 min. In microbiological assays, RESV-NP presented a MIC/MBC of 3.9 µg/mL, a time to kill of 24 h for complete eradication of H. pylori. At a concentration of 2xMIC (7.8 µg/mL), RESV-NP completely eradicated the H. pylori biofilm, and in an in vitro infection model, RESV-NP (4xMIC - 15.6 µg/mL) showed a significant decrease in bacterial load (1 Log10CFU/mL) when compared to the H. pylori J99 control. In addition, they did not demonstrate a toxic character at MIC concentration for both cell lines. The use of the RESV-NP with mucoadhesion profile is an interesting strategy for oral administration of substances targeting gastric disorders, linked to H. pylori infections.

Novel resveratrol smart lipids; design, formulation, and biological evaluation of anticancer activity.

PURPOSE: Although resveratrol (RES) is an efficacious molecule, its therapeutic activity is impeded by significant limitations, such as rapid oral absorption, poor oral bioavailability, and low water solubility. Therefore, the preparation of RES in different pharmaceutical carriers represents an important tool to enhance its therapeutic applications. This study aims to potentiate the anti-cancer activity of RES by formulating it into a novel nanocarrier called Smart Lipid. METHODS: RES-loaded Smart Lipids were prepared by high-shear hot homogenization method utilizing a 21 × 32 factorial design with three factors at different levels: the total lipid concentration, the concentration of surfactant, and the type of surfactant. The responses were evaluated based on entrapment efficiency percentages and particle size. RESULTS: Our novel optimized RES-loaded Smart Lipid formula showed small particle size (288.63 ± 5.55 nm), good zeta potential (-16.44 ± 0.99 mV), and an entrapment efficiency of 86.346 ± 3.61% with spherical, clearly distinct, and no signs of fusion by transmission electron microscopy. Further characterization was done using differential scanning calorimetry, which showed no interaction between the drug and other components as the optimum lyophilized formula showed a peak at 54.75°C, which represents the lipid mixture, with an undetectable characteristic peak of the drug, which indicates entrapment of the drug, and the structure of the compounds was confirmed by Fourier transform-infrared spectroscopy, in which the majority of the drug's characteristic peaks disappeared when loaded into Smart Lipid, which may indicate Smart Lipid's ability to reduce the stretching and bending between bonds in RES. In addition, the optimized formula showed a sustained release pattern compared to RES suspension. Finally, the cytotoxic activity of the optimized RES-loaded Smart Lipid on different cell lines (human breast adenocarcinoma (MCF7), human hepatocellular carcinoma (HepG2), and human colon cancer cells (HT29)) was assessed through MTT assay (7-fold reduction in the IC50, from 3.7 ± 0.5 µM for free RES to 0.5 ± 0.033 µM for Smart Lipid loaded formula against MCF7, 3-fold reduction in the IC50 against HepG2 cells, from 10.01 ± 0.35 to 3.16 ± 0.21 µMm, and a more than 10-fold reduction in the IC50 from more than 100 to 10 ± 0.57 µM against HT-29 cells) and its effect on cell cycle progression and apoptosis induction were assessed using flow cytometry and annexin V kit, respectively. Our results showed that RES-loaded Smart Lipid significantly reduced cell viability, induced cell cycle arrest at G0/G1 phase, and apoptosis compared to free formula and free RES suspension. CONCLUSION: Loading RES into this novel kind of nanocarrier enhanced RES absorption, cellular accumulation, and improved its anticancer properties.

Targeting vascular disrupting agent-treated tumor microenvironment with tissue-penetrating nanotherapy.

Cancer treatment with vascular disrupting agents (VDAs) causes rapid and extensive necrosis in solid tumors. However, these agents fall short in eliminating all malignant cells, ultimately leading to tumor regrowth. Here, we investigated whether the molecular changes in the tumor microenvironment induced by VDA treatment sensitize the tumors for secondary nanotherapy enhanced by clinical-stage tumor penetrating peptide iRGD. Treatment of peritoneal carcinomatosis (PC) and breast cancer mice with VDA combretastatin A-4 phosphate (CA4P) resulted in upregulation of the iRGD receptors αv-integrins and NRP-1, particularly in the peripheral tumor tissue. In PC mice treated with CA4P, coadministration of iRGD resulted in an approximately threefold increase in tumor accumulation and a more homogenous distribution of intraperitoneally administered nanoparticles. Notably, treatment with a combination of CA4P, iRGD, and polymersomes loaded with a novel anthracycline Utorubicin (UTO-PS) resulted in a significant decrease in the overall tumor burden in PC-bearing mice, while avoiding overt toxicities. Our results indicate that VDA-treated tumors can be targeted therapeutically using iRGD-potentiated nanotherapy and warrant further studies on the sequential targeting of VDA-induced molecular signatures.

Co-administration of either curcumin or resveratrol with cisplatin treatment decreases hepatotoxicity in rats via anti-inflammatory and oxidative stress-apoptotic pathways.

Background: Cisplatin (CIS) is a broad-spectrum anticancer drug, with cytotoxic effects on either malignant or normal cells. We aimed to evaluate the hepatotoxicity in rats caused by CIS and its amelioration by the co-administration of either curcumin or resveratrol. Materials and Methods: Forty adult male rats divided into four equal groups: (control group): rats were given a saline solution (0.9%) once intraperitoneally, daily for the next 28 days; (cisplatin group): rats were given a daily oral dose of saline solution (0.9%) for 28 days after receiving a single dose of cisplatin (3.3 mg/kg) intraperitoneally for three successive days; (CIS plus curcumin/resveratrol groups): rats received the same previous dose of cisplatin (3.3 mg/kg) daily for three successive days followed by oral administration of either curcumin/resveratrol solution at a dose of (20 mg/kg) or (10 mg/kg) consequently daily for 28 days. Different laboratory tests (ALT, AST, ALP, bilirubin, oxidative stress markers) and light microscopic investigations were done. Results: Administration of CIS resulted in hepatotoxicity in the form of increased liver enzymes, oxidative stress markers; degenerative and apoptotic changes, the co-administration of CIS with either curcumin or resveratrol improved hepatotoxicity through improved microscopic structural changes, reduction in liver enzymes activity, decreased oxidative stress markers, improved degenerative, and apoptotic changes in liver tissues. Conclusion: Co-administration of either curcumin or resveratrol with cisplatin treatment could ameliorate hepatotoxicity caused by cisplatin in rats via anti-inflammatory and oxidative stress-apoptotic pathways.

Cajaninstilbene acid ameliorates depression-like behaviors in mice by suppressing TLR4/NF-κB mediated neuroinflammation and promoting autophagy.

Depression is a life-threatening neurodegenerative disease lacking a complete cure. Cajaninstilbene acid (CSA), a potent stilbene compound, has demonstrated neuroprotective effects, however, studies on its antidepressant mechanisms are still scarce. This study examined the effects of CSA on lipopolysaccharide (LPS)-induced and chronic unpredictable mild stress (CUMS)-induced depression in mice, investigating its mechanisms related to inflammation and autophagy. Mice were treated with CSA (7.5, 15, and 30 mg/kg) daily for 3 weeks before intraperitoneal LPS injection (0.8 mg/kg). Another cohort underwent the same doses of CSA (7.5-30 mg/kg) daily for 6 weeks in accompany with CUMS stimulation. Behavioral assessments were conducted, and cortical samples were collected for molecular analysis. Findings indicate that CSA ameliorated depressive behaviors induced by both LPS and CUMS. Notably, CSA (15 mg/kg) reversed despair behavior in mice more persistently than amitriptyline, indicating that optimal doses of CSA may effectively decelerate the procession of mood despair and yield a good compliance. CSA countered CUMS-induced activation of TLR4/NF-κB pathway and the reduction in autophagy levels. Furthermore, CSA attenuated the CUMS-induced decline in neuroplasticity. Collectively, these findings suggest that CSA mitigates depression-like behaviors in mice by inhibiting TLR4/NF-κB-mediated neuroinflammation and enhancing autophagy. This research provides further insights into CSA's mechanisms of action in ameliorating depressive behaviors, offering a scientific foundation for developing CSA-based antidepressants.

Sorting and cryopreservation of goat sperm with or without phenolic compounds / Seleção e criopreservação de espermatozoides caprinos com ou sem compostos fenólicos

The objectives of this study were to evaluate goat sperm sorting in continuous Percoll® density gradients and gamete freezability, in the presence or absence of phenolic antioxidants. For this, semen pools were sorted, frozen, and evaluated. The non-selected group (NSg) presented lower progressive motility (PM), linearity (LIN), straightness (STR), and wobble (WOB) than the selected groups, and straight line velocity (VSL) compared to those with catechin or resveratrol. The amplitude of lateral head displacement (ALH) was higher in NSg, and quercetin reduced the mitochondrial membrane potential (MMP). After thawing, the NSg presented lower PM than the selected groups, VSL and VAP (average path velocity) than the selected group with or without catechin, LIN and WOB than the selected with or without catechin or resveratrol, and STR than the selected with catechin. Moreover, NSg presented higher ALH and BCF than the samples selected with or without catechin. Plasma membrane integrity and intact and living cells were higher in the selected groups, and MMP was lower in the NSg and the selected group with quercetin. Thus, centrifugation in Percoll® continuous density gradients is a viable methodology to select goat sperm compatible with the freezing, especially in the presence of catechin or resveratrol.(AU)

Objetivou-se avaliar a separação de espermatozoides caprinos em gradientes de densidade contínuos de Percoll® e a congelabilidade espermática, com ou sem antioxidantes fenólicos. Para tal, pools seminais foram selecionados, congelados e avaliados. O grupo não selecionado (gNS) apresentou menor motilidade progressiva (MP), linearidade (LIN), retilinearidade (STR) e oscilação (WOB) do que os selecionados, bem como menor velocidade linear progressiva (VSL) do que os com catequina ou resveratrol. A amplitude de deslocamento lateral de cabeça (ALH) foi maior no gNS e a quercetina reduziu o potencial de membrana mitocondrial (PMM). Após a descongelação, o gNS manifestou menor MP do que os selecionados, menor VSL e VAP (velocidade média da trajetória) do que os com ou sem catequina, menor LIN e WOB do que os com ou sem catequina ou resveratrol, e menor STR do que os com catequina, além de maior ALH e BCF do que os com ou sem catequina. A integridade da membrana plasmática e as células intactas e vivas foram maiores nas amostras selecionadas e o PMM foi inferior no gNS e no selecionado com quercetina. Portanto, a centrifugação em gradientes contínuos de densidade de Percoll® é uma metodologia viável para selecionar espermatozoides caprinos compatíveis com a congelação, especialmente na presença de catequina ou resveratrol.(AU)

Neuroprotective potential of polydatin against motor abnormalities and dopaminergic neuronal loss in rotenone induced Parkinson model / Potencial neuroprotector de la polidatina contra las anomalías motoras y la pérdida neuronal dopaminérgica en un modelo de Parkinson inducido por la rotenona

Among the neurodegenerative disorders, Parkinson disease (PD) is ranked as second most common. The pathological hallmark is selective degeneration of the dopaminergic neurons in the nigro-striatal regions of brain with appearance of the Lewy bodies. Present study explores the neuro-protective potential of polydatin in terms of amelioration of degeneration of dopaminergic neurons in nigro-striatal regions of brain and distorted neuromotor behavior in the rotenone model of Parkinson's disease. Thirty-six male Sprague Dawley rats were divided into three groups. Group A (control), Group B (rotenone treated) and Group C (rotenone+polydatin treated). Rotenone was administrated intraperitoneally (i.p) at a dose of 3 mg/kg/body weight while polydatin was given i.p. at a dose of 50 mg/ kg/body weight for four weeks. Then, animals were sacrificed; substantia nigra (SN) & striatum isolated from brain and five micron thick sections were prepared. Cresyl violet (CV), H&E and Immuno-histochemical staining using anti-TH antibody was done. Motor behavior was assessed weekly throughout the experiment using five different methods. Rotenone treated parkinsonian animals showed deterioration of motor behavior, weight loss, loss of dopaminergic neurons and diminished immune-reactivity in the sections from the nigrostriatal regions of these animals Polydatin+rotenone treatment showed contradicting effects to parkinsonism, with amelioration in weight loss, neuro-motor behavior, dopaminergic loss and immune-reactivity against dopaminergic neurons. Present study revealed a neuro-protective potential of polydatin in animal model of PD by ameliorating the neuro-motor abnormalities and degeneration of dopaminergic neurons in nigrostriatal regions.

Entre los trastornos neurodegenerativos, la enfermedad de Parkinson (EP) se clasifica como la segunda más común. El sello patológico es la degeneración selectiva de las neuronas dopaminérgicas en las regiones nigro-estriatales del cerebro, con la aparición de los cuerpos de Lewy. El presente estudio explora el potencial de protección neuronal de la polidatina en términos de la mejora de la degeneración de las neuronas dopaminérgicas en las regiones nigro-estriatales del cerebro y el comportamiento neuromotor distorsionado en el modelo de rotenona de la enfermedad de Parkinson. Treinta y seis ratas macho Sprague Dawley se dividieron en tres grupos: Grupo A (control), Grupo B (tratado con rotenona) y Grupo C (tratamiento con rotenona + polidatina). La rotenona se administró por vía intraperitoneal (i.p.) a una dosis de 3 mg/kg/peso corporal, mientras que la polidatina se administró i.p. a una dosis de 50 mg/kg/ peso corporal durante cuatro semanas. Posteriormente, los animales fueron sacrificados. Se aislaron la substantia nigra (SN) y cuerpo estriado de los cerebros y se realizaron secciones de cinco micras de espesor. Se realizó una tinción de violeta de cresilo (CV), H&E y tinción inmunohistoquímica usando anticuerpo anti-TH. El comportamiento motriz se evaluó semanalmente durante todo el experimento utilizando cinco métodos diferentes. Los animales parkinsonianos tratados con rotenona mostraron deterioro del comportamiento motriz, pérdida de peso, pérdida de neuronas dopaminérgicas y disminución de la reactividad inmune en las secciones de las regiones nigroestriadas. El tratamiento con polidatina + rotenona mostró efectos contrarios al parkinsonismo, con mejoría en la pérdida de peso, en el comportamiento motor, en la pérdida dopaminérgica y en la reactividad inmune contra las neuronas dopaminérgicas. El presente estudio reveló un potencial de protección neuronal de la polidatina en el modelo animal de la EP al mejorar las anomalías neuro-motoras y la degeneración de las neuronas dopaminérgicas en las regiones nigroestriatales.

Protective effect of resveratrol against morphine damage to kidneys of mice / Efecto protector de resveratrol contra el daño de la morfina en riñones de ratones

SUMMARY: Morphine produces free radicals and cause apoptosis in some cell. Resveratrol (RSV) is a stilbenoid, a type of natural phenol, and a phytoalexin produced by several plants in response to injury. 48 male mice were randomly assigned to 8 groups. In this study, various doses of RSV (2, 8 and 20 mg/kg) and RSV plus Morphine (2, 8 and 20 mg/kg) were administered intraperitoneally to male mice for 20 consequent days and weight of kidneys, biochemical characteristics, morphometric markers and blood serum nitric oxide level were studied. The results indicated that morphine administration significantly increased the mean diameter of glomerulus and distal and proximal convoluted tubule, Lactate dehydrogenase (LDH), Blood urea nitrogen (BUN), creatinine and nitric oxide levels compared to the saline group (P<0.05). However, RSV and RSV plus morphine in all doses significantly decreased glomeruli number and LDH, BUN, creatinine and nitric oxide levels compared to morphine groups (p<0.05). Thus, it seems that resveratrol improved kidney damages induced by morphine in mice.

RESUMEN: La morfina produce radicales libres y causa apoptosis en algunas células. El resveratrol (RSV) es un tipo de fenol natural y una fitoalexina producida por varias plantas en respuesta a una lesión. Se asignaron al azar 48 ratones machos a 8 grupos. En este estudio se administraron varias dosis de RSV (2, 8 y 20 mg/kg) y RSV más morfina (2, 8 y 20 mg/kg) intraperitoneal en ratones machos durante 20 días consecutivos y se estudió el peso de los riñones, las características bioquímicas, los marcadores morfométricos y el nivel de óxido nítrico en suero sanguíneo. Los resultados indicaron que la administración de morfina aumentó significativamente el diámetro medio del glomérulo y de los túbulos distal y proximal, los niveles de lactato deshidrogenasa (LDH), nitrógeno ureico en sangre (BUN), la creatinina y el óxido nítrico en comparación con el grupo salino (p <0,05). Sin embargo, el RSV y el RSV más morfina en todas las dosis redujeron significativamente el número de glomérulos y LDH, BUN, la creatinina y el óxido nítrico en comparación con los grupos de morfina (p <0,05). Por lo tanto, los resultados podrían indicar que el resveratrol mejoró el daño renal inducido por la morfina en ratones.

Therapeutic effect of resveratrol on morphine-induced damage in male reproductive system of mice by reducing nitric oxide serum level / Efecto terapéutico de resveratrol sobre el daño inducido por la morfina en el sistema reproductor masculino de ratones reduciendo el nivel de óxido nítrico del suero

SUMMARY: Morphine is one of the naturally occurring phenanthrene alkaloids of opium that induces adverse effects on male reproductive system. Resveratrol is a phytoestrogen and antioxidant of red grape. The main goal is to investigate whether resveratrol could inhibit adverse effects of morphine on sperm cell viability, count, motility as well as testis histology, testosterone hormone and nitric oxide levels in mice. In the present study, 48 male rats were randomly divided into 8 groups (n=6) and were treated intraperitoneally for 14 days with normal saline, resveratrol (2, 8, 20 mg/kg/day), morphine (20 mg/kg/day) and morphine (20 mg/kg/day) + resveratrol (2, 8, 20 mg/kg/day). At the end of experiments, sperm parameters (sperm cell viability, count, motility and morphology), testis weight, the diameter of seminiferous tubules, testosterone hormone level and nitric oxide were analyzed. The data were analyzed by SPSS software for windows (version 20) using one-way ANOVA test followed by Tukey's post hoc test, and P<0.05 was considered significant. The results indicated that morphine administration significantly decreased testosterone level, count, viability and motility of sperm cells and testis weight and increased nitric oxide compared to the saline group (P=0.000). Administration of resveratrol and resveratrol plus morphine significantly increased motility, count and viability of sperm cells, somniferous tubule diameter and testosterone, while it decreased nitric oxide level compared to morphine group (P=0.025). It seems that resveratrol administration could increase the quality of spermatozoa and prevented morphine-induced adverse effects on sperm parameters.

RESUMEN: La morfina es uno de los alcaloides fenantreno del opio que induce efectos adversos en el sistema reproductivo masculino. El resveratrol es un fitoestrógeno y antioxidante de la uva roja. El objetivo principal de este trabajo fue investigar si el resveratrol puede inhibir los efectos adversos de la morfina sobre la viabilidad celular de los espermatozoides, el recuento y la motilidad, así como la histología de los testículos, la hormona testosterona y los niveles de óxido nítrico en ratones. Se dividieron, aleatoriamente, 48 ratas machos en 8 grupos (n = 6) y se trataron de forma intraperitoneal durante 14 días con solución salina normal, resveratrol (2, 8, 20 mg / kg / día), morfina (20 mg / kg / día ) y morfina (20 mg / kg / día) + resveratrol (2, 8, 20 mg / kg / día). Al final de los experimentos, se analizaron los parámetros espermáticos (viabilidad celular, recuento, motilidad y morfología), el peso de los testículos, el diámetro de los túbulos seminíferos, el nivel de la hormona testosterona y el óxido nítrico. Los datos fueron analizados con el software de SPSS para Windows (versión 20) usando una prueba de ANOVA de una vía seguida de la prueba post hoc de Tukey, y P <0,05 se consideró significativo. Los resultados indicaron que la administración de morfina disminuyó significativamente el nivel de testosterona, el recuento, la viabilidad y la motilidad de los espermatozoides y el peso de los testículos, además del aumento de óxido nítrico en comparación con el grupo salino (p = 0,000). La administración de resveratrol y resveratrol más morfina aumentó significativamente la motilidad, el recuento y la viabilidad de los espermatozoides, el diámetro de los túbulos seminíferos y la testosterona, mientras que disminuyó el nivel de óxido nítrico comparado con el grupo morfina (p = 0,025). En conclusión, la administración de resveratrol podría aumentar la calidad de los espermatozoides y prevenir los efectos adversos inducidos por la morfina sobre los parámetros espermáticos.

Compuestos bioactivos e inflamaciónligada a obesidad / Bioactive compounds and inflammation linked to obesity

Obesity has emerged among the major worldwide health threats. This pathology is characterized by the presence of a chronic inflammatory state in the overgrowing adipose tissue. This state has been related with an increased monocyte infiltration, and consequently with an establishment of an adipocyte-macrophage interaction, which in turn has been linked with the onset of obesity-related insulin resistance. Consequently, reducing this pathogenic crosstalk could comprise an interesting approach to counteract this inflammation. In this context, the screening of natural compounds with known anti-inflammatory/antioxidant properties over this crosstalk could be of highly significance. Popular culture and some investigations have point out that foods richs in polyphenols and essential fatty acids are known to possess these characteristics. It has been described that isolated bioactive compounds presents promising beneficial properties against the expression or secretion of inflammatory markers that are induced by the adipocyte-macrophage communication. Therefore, the proper evaluation of these compounds or the identification of new ones with potential characteristics is actually needed in aiming to reduce the increasing tendency of obesity-related pathologies, such as type 2 diabetes...

The qualitative effects of resveratrol and coenzyme Q10 administration on the gluteus complex muscle morphology of SJL/J mice with dysferlinopathy / Efectos cualitativos de la administración de resveratrol y coenzima Q10 en la morfología del complejo muscular glúteo de ratones SJL/J con disferlinopatía

Dysferlinopathy is a form of muscular dystrophy affecting muscles of the shoulder and pelvic girdles, resulting from inheritance of a mutated dysferlin gene. The encoded dysferlin protein is proposed to be involved in sarcolemmal vesicle fusion with a disrupted plasma membrane; however, with defective protein function these vesicles accumulate beneath the disruption site but are unable to fuse with it and reseal the membrane, thus rendering the membrane repair mechanism defective. The SJL/J mouse model presents with characteristics much like the commonest human condition. Immune modulators have long been under study in the maintenance of muscle health in muscular dystrophies. Such supplementary treatment would ideally suppress inflammation, preventing the immune response toward degenerating muscle from causing additional muscle fiber death, and thus provide a mechanism by which to prolong the life of muscle fibers with inherently defective healing apparatus. For this purpose the anti-inflammatory supplement resveratrol and the membrane-protective supplement coenzyme Q10 were administered separately and in combination to experimental animals to determine their effectiveness in possible therapy of dysferlinopathy. The findings of this study report that low doses of resveratrol and coenzyme Q10 supplementation in exclusivity were unable to afford much protection to muscle fibers at the tissue level. High doses of coenzyme Q10 proved more effective in reducing attenuating inflammation; and combination treatment with resveratrol and coenzyme Q10 provided not only the membrane-protective effects of coenzyme Q10, but also the anti-inflammatory effects of resveratrol which failed to materialize at sufficient levels in exclusive administration.

Disferlinopatía es una forma de distrofia muscular que afecta a los músculos de los hombros y cintura pélvica, resultado de la herencia y mutación del gen de la distrofina. Sugerimos que la proteína codificada distrofina que integra la estructura sarcolemal con una membrana plasmática interrumpida, que al presentar una proteína defectuosa, las estructuras se acumulan debajo del sitio de alteración sin lograr fundirse con éste y cerrar la membrana afectando el mecanismo de reparación. El modelo de ratón SJL / J se presenta con características muy similares a una condición humana común. Los inmunomoduladores han sido objeto de estudio en el mantenimiento de la salud muscular en las distrofias musculares. Este tipo de tratamiento suplementario puede ser ideal para suprimir la inflamación, en la prevención de la respuesta inmune en la degeneración muscular causando la muerte adicional de fibra muscular, y al mismo tiempo proporcionar, un mecanismo con el cual prolongar la vida útil de aquellas fibras musculares con el aparato de sanación comprometido. Para ello, el Resveratrol suplemento anti-inflamatorio y el suplemento protector de membrana coenzima Q10 se administró por separado y en combinación en los animales de laboratorio para determinar su efectividad en el tratamiento de posible disferlinopatía. Los resultados de este estudio indican que el Resveratrol en menor dosis y la coenzima Q 10 administrados como suplementos de manera exclusiva, no demostraron efectos de protección de las fibras musculares a nivel del tejido. Una alta dosis de coenzima Q10 demostró ser más efectiva en la reducción de la inflamación; adicionalmente, el tratamiento combinado de Resveratrol y coenzima Q10 proporcionó efectos protectores de membrana, además de los efectos anti-inflamatorios del Resveratrol cuyo nivel no alcanzó la efectividad suficiente al ser administrado en forma exclusiva.