Dioclea violacea lectin inhibits tumorigenesis and tumor angiogenesis in vivo.

Dioclea violacea seed mannose-binding lectin (DvL) has attracted considerable attention because of its interesting biological activities, including antitumor, antioxidant, and anti-inflammatory activities. This study evaluated the cytotoxic effect of DvL on tumor and normal cells using the mitochondrial activity reduction (MTT) assay, the carcinogenic and anti-carcinogenic activity by the epithelial tumor test (ETT) in Drosophila melanogaster, and the anti-angiogenic effect by the chick embryo chorioallantoic membrane (CAM) assay. Data demonstrated that DvL promoted strong selective cytotoxicity against tumor cell lines, especially A549 and S180 cells, whereas normal cell lines were weakly affected. Furthermore, DvL did not promote carcinogenesis in D. melanogaster at any concentration tested, but modulated DXR-induced carcinogenesis at the highest concentrations tested. In the CAM and immunohistochemical assays, DvL inhibited sarcoma 180-induced angiogenesis and promoted the reduction of VEGF and TGF-ß levels at all concentrations tested. Therefore, our results demonstrated that DvL is a potent anticancer, anti-angiogenic, and selective cytotoxic agent for tumor cells, suggesting its potential application as a prototype molecule for the development of new drugs with chemoprotective and/or antitumor effects.

Tellimagrandin-I and camptothin a exhibit chemopreventive effects in Salmonella enterica serovar Typhimurium strains and human lymphocytes.

Tellimagrandin-I (TL) and camptothin A (CA) are ellagitannins widely found in diverse plant species. Numerous studies demonstrated their significant biological activities, which include antitumor, antioxidant, and hepatoprotective properties. Despite this protective profile, the effects of TL and CA on DNA have not been comprehensively investigated. Thus, the aim of this study was to determine the mutagenic and antimutagenic effects attributed to TL and CA exposure on Salmonella enterica serovar Typhimurium strains using the Ames test. In addition, the cytotoxic and genotoxic effects were examined on human lymphocytes, employing both trypan blue exclusion and CometChip assay. The antigenotoxic effect was determined following TL and CA exposure in the presence of co-treatment with doxorubicin (DXR). Our results from the Ames test indicated that TL or CA did not display marked mutagenic activity. However, TL or CA demonstrated an ability to protect DNA against the damaging effects of the mutagens 4-nitroquinoline-1-oxide and sodium azide, thereby exhibiting antimutagenic properties. In relation to human lymphocytes, TL or CA did not induce significant cytotoxic or genotoxic actions on these cells. Further, these ellagitannins exhibited an ability to protect DNA from damage induced by DOX during co-treatment, indicating their potential beneficial usefulness as antigenotoxic agents. In conclusion, the protective effects of TL or CA against mutagens, coupled with their absence of genotoxic and cytotoxic effects on human lymphocytes, emphasize their potential therapeutic value in chemopreventive strategies.

Pedunculagin and tellimagrandin-I stimulate inflammation and angiogenesis and upregulate vascular endothelial growth factor and tumor necrosis factor-alpha in vivo.

Pedunculagin (PD) and tellimagrandin-I (TL), isolated from Myrciaria cauliflora seeds and Eucaliptus microcorys leaves, respectively, have attracted great attention owing to their relevant biological activities, such as antitumor, antioxidant, and hepatoprotective activities. This study investigated the angiogenic potential of PD and TL using a chick embryo chorioallantoic membrane (CAM) assay. Using the CAM assay, our results showed that both PD and TL promoted a significant increase in the number and caliber of blood vessels, the thickness of the CAM, and the presence of fibroblasts and inflammatory cells. Moreover, an increase of tumor necrosis factor-α and vascular endothelial growth factor was observed in the CAM treated with PD and TL, indicating the induction of angiogenic factors. Thus, the remarkable profile of PD and TL in inducing angiogenesis opens up new perspectives for their potential utilization in different therapeutic approaches involving neovascularization.

Chemopreventive effect and induction of DNA repair by oenothein B ellagitannin isolated from leaves of Eugenia uniflora in Swiss Webster treated mice.

Oenothein B (OeB) is a dimeric ellagitannin with potent antioxidative, antitumor, immunomodulatory, and anti-inflammatory properties. Despite the promising activities of OeB, studies examining the genotoxic or protective effects of this ellagitannin on DNA are scarce. Therefore, to further comprehensively elucidate the chemopreventive profile of OeB, the aim of this study was to evaluate the mutagenic and antimutagenic actions of OeB using Salmonella typhimurium strains with the Ames test. The micronucleus (MN) test and comet assay were used to assess the anticytotoxic and antigenotoxic effects of OeB on mouse bone marrow cells following differing treatments (pre-, co-, and post-treatment) in response to cyclophosphamide (CPA)-induced DNA damage. In addition, histopathological analyses were performed to assess liver and kidney tissues of Swiss Webster treated mice. Our results did not detect mutagenic or antimutagenic activity attributed to OeB at any concentration in the Ames test. Regarding the MN test, data showed that this ellagitannin exerted antigenotoxic and anticytotoxic effects against CPA-induced DNA damage under all treatment conditions. However, no anticytotoxic action was observed in MN test after pre-treatment with the highest doses of OeB. In addition, OeB demonstrated antigenotoxic effects in the comet assay for all treatments. Histopathological analyses indicated that OeB attenuated the toxic effects of CPA in mouse liver and kidneys. These findings suggest that OeB exerted a chemoprotective effect following pre- and co-treatments and a DNA repair action in post-treatment experiments. Our findings indicate that OeB protects DNA against CPA-induced damaging agents and induces post-damage DNA repair.

Immunogenic Cell Death Photothermally Mediated by Erythrocyte Membrane-Coated Magnetofluorescent Nanocarriers Improves Survival in Sarcoma Model.

Inducing immunogenic cell death (ICD) during cancer therapy is a major challenge that might significantly improve patient survival. The purpose of this study was to develop a theranostic nanocarrier, capable both of conveying a cytotoxic thermal dose when mediating photothermal therapy (PTT) after its intravenous delivery, and of consequently inducing ICD, improving survival. The nanocarrier consists of red blood cell membranes (RBCm) embedding the near-infrared dye IR-780 (IR) and camouflaging Mn-ferrite nanoparticles (RBCm-IR-Mn). The RBCm-IR-Mn nanocarriers were characterized by size, morphology, surface charge, magnetic, photophysical, and photothermal properties. Their photothermal conversion efficiency was found to be size- and concentration-dependent. Late apoptosis was observed as the cell death mechanism for PTT. Calreticulin and HMGB1 protein levels increased for in vitro PTT with temperature around 55 °C (ablative regime) but not for 44 °C (hyperthermia), suggesting ICD elicitation under ablation. RBCm-IR-Mn were then intravenously administered in sarcoma S180-bearing Swiss mice, and in vivo ablative PTT was performed five days later. Tumor volumes were monitored for the subsequent 120 days. RBCm-IR-Mn-mediated PTT promoted tumor regression in 11/12 animals, with an overall survival rate of 85% (11/13). Our results demonstrate that the RBCm-IR-Mn nanocarriers are great candidates for PTT-induced cancer immunotherapy.

Protective effects and DNA repair induction of a coumarin-chalcone hybrid against genotoxicity induced by mutagens.

Coumarins and chalcones are compounds widely found in plants or obtained by synthetic methods which possess several biological properties including antioxidant, anti-inflammatory, and antitumor effects. A series of coumarin-chalcone hybrids were synthesized to improve their biological actions and reduce potential adverse effects. Considering the applications of these molecules, a coumarin-chalcone hybrid [7-methoxy-3-(E)-3-(3,4,5-trimethoxyphenyl) acryloyl-2 H-chromen-2-one] (4-MET) was synthesized and the genotoxic, cytotoxic, and protective effects assessed against damage induced by different mutagens. First, in silico tools were used to predict biological activity of 4-MET which indicated a chemopreventive potential. Subsequently, the genotoxic/antigenotoxic activities of 4-MET were determined both in vitro (Ames test) and in vivo (micronucleus (MN) test and comet assay). In addition, molecular docking simulations were performed between 4-MET and glutathione reductase, an important cellular detoxifying enzyme. Our results indicated that 4-MET was not mutagenic in the Ames test; however, when co-treated with sodium azide or 4-nitroquinoline 1-oxide (4-NQO), 4-MET significantly reduced the harmful actions of these mutagens. Except for a cytotoxic effect after 120 hr treatment, 4-MET alone did not produce cytotoxicity or genotoxicity in the MN test and comet assay. Nonetheless, all treatments of 4-MET with cyclophosphamide (CPA) showed a chemoprotective effect against DNA damage induced by CPA. Further, molecular docking analysis indicated a strong interaction between 4-MET and the catalytic site of glutathione reductase. These effects may be related to (1) damage prevention, (2) interaction with detoxifying enzymes, and (3) DNA-repair induction. Therefore, data demonstrated that 4-MET presents a favorable profile to be used in chemopreventive therapies.

Lactose-binding lectin from Vatairea macrocarpa seeds induces in vivo angiogenesis via VEGF and TNF-ɑ expression and modulates in vitro doxorubicin-induced genotoxicity.

Lactose-binding lectin from Vatairea macrocarpa seeds (VML) has attracted great attention due to its interesting biological activities, such as pro-inflammatory effects and macrophage activation. This study evaluated the cytotoxicity and genotoxicity/antigenotoxicity of VML in human lymphocytes using the CometChip assay, and angiogenic activity by the chick embryo chorioallantoic membrane (CAM) assay. In genotoxicity, lymphocytes were treated with different concentrations of VML (0.5, 2 and 8 µM). In antigenotoxicity, lymphocytes were treated with the same concentrations of VML concomitant doxorubicin (90 µM DXR). To evaluate angiogenesis, all CAM were treated with different concentrations of VML (0.5, 2 and 8 µM) alone or co-treated with lactose (0.1 M). Furthermore, the levels of vascular endothelial growth factor (VEGF) and tumor necrosis factor-alpha (TNF-α) in CAM were assessed by immunohistochemistry. The results showed that VML was cytotoxic to lymphocytes, genotoxic at the highest concentration (8 µM) and antigenotoxic at low concentrations (0.5, and 2 µM). Regarding the CAM assay and immunohistochemistry, VML was angiogenic and significantly increased VEGF and TNF-α levels. In contrast, co-treatment with lactose significantly reduced the angiogenic effect and VEGF levels. We propose that protein-carbohydrate interactions between VML and glycans in the cell membrane are probably the major events involved in these activities. It seems likely that VML elicits a pro-inflammatory response through VEGF and TNF-α expression, resulting in increased vascularization at the site of inflammation. Therefore, our results show novel information on the effects of VML on DNA, as well as provide data regarded the neovascularization process involving this lectin.

Novel sulfonamide-chalcone hybrid stimulates inflammation, angiogenesis and upregulates vascular endothelial growth factor (VEGF) in vivo.

Chalcones and sulfonamides are well-known chemical groups associated with several biological activities such as antibiotic, anti-inflammatory, and antitumor activities. Over the past few decades, a series of sulfonamide-chalcone hybrids have been synthesized and assessed to develop compounds with interesting biological properties for application in disease therapy. In the present study, a new sulfonamide-chalcone hybrid µ - (2,5-dichloro-N-{4-[(3E)-4-(3-nitrophenyl) buta-1,3-dien-2-yl] phenyl} benzene sulfonamide), or simply CL185, was synthesized, and its angiogenic activity was assessed using the chick embryo chorioallantoic membrane (CAM) assay at different concentrations (12.5, 25, and 50 µg/µL). To further investigate the role of CL185 in the angiogenic process, we evaluated the levels of vascular endothelial growth factor (VEGF) in all treated CAMs. The results showed that all concentrations of CL185 significantly increased tissue vascularization (p < 0.05) as well as the parameters associated with angiogenesis, in which inflammation was the most marked phenomenon observed. In all CAMs treated with CL185, VEGF levels were significantly higher than those in the negative control (p < 0.05), and at the highest concentration, VEGF levels were even higher than in the positive control (p < 0.05). The pronounced angiogenic activity displayed by CL185 may be related to the increase in VEGF levels that were stimulated by inflammatory processes observed in our study. Therefore, CL185 presents a favorable profile for the development of drugs that can be used in pro-angiogenic and tissue repair therapies.

Pedunculagin isolated from Plinia cauliflora seeds exhibits genotoxic, antigenotoxic and cytotoxic effects in bacteria and human lymphocytes.

Pedunculagin (PD), an ellagitannin found in different plant species, possesses several pharmaceutical properties, including antitumor, antioxidant, gastroprotective, hepatoprotective, and anti-inflammatory properties. However, the effects of PD alone on DNA remain to be determined. The aim of this study was to investigate the potential cytotoxic, genotoxic, and antigenotoxic activities of PD isolated from Plinia cauliflora seeds using in silico and in vitro assays. To elucidate the biological activities of PD, in silico tools indicative of antioxidant, antineoplastic, and chemopreventive activities of PD were used. Subsequently, the mutagenic/antimutagenic effects of PD were later assessed using bacteria with the Ames test, and the cytotoxic, genotoxic, and antigenotoxic effects utilizing human lymphocytes as evidenced by trypan blue exclusion test and CometChip assay. In silico analysis indicated potential antioxidant, chemopreventive, free radical scavenger, and cytostatic activities of PD. In the Ames test, PD was found to be not mutagenic; however, this plant component protected DNA against damage-mediated by mutagens 4-nitroquinoline-1-oxide and sodium azide. Regarding human lymphocytes, PD alone was cytotoxic and genotoxic; however, it also reduced DNA damage induced by doxorubicin at co- and post-treatment. In conclusion, PD showed genotoxic, antigenotoxic and cytotoxic effects in human lymphocytes and antimutagenic effects in bacteria.

Anti-angiogenic activity of azathioprine.

Azathioprine (AZA) is the main drug used in immunomodulatory therapy in post-transplant patients or with autoimmune diseases. However, no study has evaluated the AZA angiogenic response. Therefore, this study investigated the effects of AZA on the angiogenic process through macroscopic, histological, and immunohistochemical analyses in chick embryo chorioallantoic membrane (CAM). Our results showed potent anti-angiogenic activity of AZA at the higher concentrations tested in the CAM assay. The histological analysis of CAM confirmed this effect, since AZA induced a significant reduction in all parameters evaluated. In addition, immunohistochemical evaluation of CAM revealed that AZA decreased TGF-ß and VEGF levels, important cytokines involved in the angiogenic process. Therefore, the AZA anti-angiogenic effect identified in our study provides new information for the possible application of this drug in anticancer treatment.

Prednisone is genotoxic in mice and Drosophila melanogaster.

Prednisone (PD) is one of the most commonly used corticosteroids in immunosuppressive therapy for patients with autoimmune diseases and transplants. Chronic use of corticosteroids is associated with several side effects and an increase in neoplasia. Since genotoxic effects are associated with an increased risk of cancer development, this study evaluated the genotoxic and cytotoxic activities of PD using the SMART/wing assay in Drosophila melanogaster and the micronucleus test and comet assay in mouse bone marrow cells. Further, the toxic effects of PD on mouse organ tissues were assessed using histopathological analyses. In the SMART/wing assay, PD showed a significant genotoxic activity at all concentrations tested (0.375, 0.75, 1.5, and 2.0 mg/mL) compared to the negative control (p < 0.05). The micronucleus test and comet assay also showed an elevated genotoxicity of PD at all treatment conditions (24, 48, and 120 h with doses ranging from 0.5 to 1.5 mg/kg) compared to the negative control (p < 0.05). The histopathological analyses did not show toxicity of PD in mouse cells and tissues. Therefore, our results demonstrate that PD is a potent genotoxic immunosuppressant in mice and D. melanogaster cells. Somatic recombination was the primary contributor (46%-82%) to the induced genotoxicity observed in the SMART test.

Effects of moderate aerobic exercise on thoracic aortic remodeling of female LDL-receptor knockout ovariectomized mice.

Menopause is a major factor involved in dyslipidemia increasing the risk of atherosclerosis which may be reversed by a routine of aerobic physical activity. Thus, this study aimed to analyze the effects of aerobic training on the thoracic aorta of female LDL-receptor knockout mice submitted to estrogen deprivation. Fifteen genetically modified female mice, knockout for the low-density lipoprotein receptor (LDL-Knockout group) were used as experimental groups and fifteen wild female mice (C57BL/6 J) were used as control groups. Animals were divided as (n = 5/per group): sedentary control (SC); sedentary control ovariectomized (SCO); trained control ovariectomized (TCO); LDL-Knockout sedentary (KS); LDL-Knockout sedentary ovariectomized (KOS); and LDL-Knockout trained ovariectomized (KOT). Immunohistochemical techniques for TIMP-1 and metalloproteinases 2 and 9 were used to evaluate thoracic aorta remodeling. Picrosirius stain was used to highlight the collagen fibers. Verhoff-Van Gienson was used for the quantitative analyses of elastic lamellae. Our results demonstrate a positive remodeling promoted by physical exercise in ovariectomized and dyslipidemic animals. However, further studies are needed including the evaluation of inflammatory markers present in dyslipidemia.

Effects of moderate aerobic exercise on thoracic aortic remodeling of female LDL-receptor knockout ovariectomized mice

Menopause is a major factor involved in dyslipidemia increasing the risk of atherosclerosis which may be reversed by a routine of aerobic physical activity. Thus, this study aimed to analyze the effects of aerobic training on the thoracic aorta of female LDL-receptor knockout mice submitted to estrogen deprivation. Fifteen genetically modified female mice, knockout for the low-density lipoprotein receptor (LDL-Knockout group) were used as experimental groups and fifteen wild female mice (C57BL/6 J) were used as control groups. Animals were divided as (n = 5/per group): sedentary control (SC); sedentary control ovariectomized (SCO); trained control ovariectomized (TCO); LDL-Knockout sedentary (KS); LDL-Knockout sedentary ovariectomized (KOS); and LDL-Knockout trained ovariectomized (KOT). Immunohistochemical techniques for TIMP-1 and metalloproteinases 2 and 9 were used to evaluate thoracic aorta remodeling. Picrosirius stain was used to highlight the collagen fibers. Verhoff-Van Gienson was used for the quantitative analyses of elastic lamellae. Our results demonstrate a positive remodeling promoted by physical exercise in ovariectomized and dyslipidemic animals. However, further studies are needed including the evaluation of inflammatory markers present in dyslipidemia.

Physical exercise alters hepatic morphology of low-density lipoprotein receptor knockout ovariectomized mice.

To explore the effects of physical exercise on the liver of animals in menopause, we analyzed the histomorphometric parameters of the hepatic tissue in ovariectomized and dyslipidemic female mice. The animals were distributed in six groups (n = 5): sedentary control (SC), sedentary ovariectomized control (SOC), trained ovariectomized control (TOC), sedentary LDL knockout (LDL-S), sedentary ovariectomized LDL knockout (LDL-SO), and trained ovariectomized LDL knockout (LDL-TO). At the end of the experiment, the liver and the visceral adipose tissue (VAT) of animals were removed for morphometric and stereological studies. In the LDL-S and LDL-SO animals, both sedentary, results showed reduction in the area (µm2) and major and minor diameters (µm) of hepatocytes and reduction in the portions of large hepatocytes, and increase in the percentage of Kupffer cells. The trained group showed a tendency of increase in the area and diameter and in the percentage of hepatocytes, as well significant reduction in the percentage of Kupffer cells and interstitial tissue. We suggested that training can prevent cell and tissue damage caused by the process of increase in hepatic fat, lipoperoxidation, and tissue inflammation in animals with privation of estrogen and dyslipidemia, apparently reflecting a better metabolic response of the hepatic tissue in organisms undergoing training.

Effect of mild aerobic exercise in atrial granules of mice with chronic Chagas Disease / Efeito do exercício aeróbico leve em grânulos atriais de camundongos com doença de Chagas crônica

Background: Chagas disease presents in different clinical forms, ranging from asymptomatic to acute, with destruction of heart cells and a possibility of death. In the chronic phase, the parasites can cause serious injuries to different tissues.Objectives: Our objective was to study the effects of physical exercise (swimming) in atrial granules and components of cardiomyocytes in mice with chronic Chagas disease. Methods: In total, 20 male mice were divided into four different groups: untrained control (UC), trained control (TC), untrained infected (UI), and trained infected (TI). In the UI and TI groups, 1,000 forms of Trypanosoma cruzi (Y strain) were inoculated intraperitoneally. After 40 days of infection and proof of chronic phase, the exercise protocol began. The UC and UI groups performed exercise for 10 min/day, and the TC and TI groups followed a training protocol five times a week for 30 minutes during 8 weeks. Ultrathin sections were subjected to morphometric and stereological analyses using electron photomicrographs (x15000) obtained by transmission electron microscopy.Results: The TI group showed the lowest percentage of small granules (58%), while the UI group presented 80% of these granules. The volume density of the Golgi complex and myofibrils in the TI group were reduced compared with those in the UI group, while the parameters of atrial granules and mitochondria increased. Conclusion: Our results suggest that mild physical exercise changes the morphological and morphometric parameters of granules and organelles in the cardiac atrium of mice infected with T. cruzi, and produces moderate beneficial effects on the cardiovascular system

Acute toxic effects of ruthenium (II)/amino acid/diphosphine complexes on Swiss mice and zebrafish embryos.

Anticancer potential of ruthenium complexes has been widely investigated, but safety evaluation studies are still scarce. Despite of ruthenium-based anticancer agents are known to cause fewer side effects compared to other metal-based drugs, these compounds are not fully free of toxicity, causing mainly nephrotoxicity. Based on the promising results from antitumor activity of the complexes [Ru(L-Met)(bipy)(dppb)]PF6 (RuMet) and [Ru(L-Trp)(bipy)(dppb)]PF6 (RuTrp), for the first time we investigated the toxicity profile of these complexes in rodent and zebrafish models. The acute oral toxicity was evaluated in Swiss mice. The mutagenic and genotoxic potential was determined by a combination of Micronucleus (MN) and Comet assay protocols, after exposure of Swiss mice to RuMet and RuTrp in therapeutic doses. Zebrafish embryos were exposed to these complexes, and their development observed up to 96 h post-fertilization. RuMet and RuTrp complexes showed low acute oral toxicity. Recorded behavioral changes were not recorded, nor were macroscopic morphological changes or structural modifications in the liver and kidneys. These complexes did not cause genetic toxicity, presenting a lack of micronuclei formation and low DNA damage induction in the cells from Swiss mice. In contradiction, cisplatin treatment exhibited high mutagenicity and genotoxicity. RuMet and RuTrp showed low toxicity in the embryo development of zebrafish. The RuMet and RuTrp complexes demonstrated low toxicity in the two study models, an interesting property in preclinical studies for novel anticancer agents.

Chikungunya surveillance in Brazil: challenges in the context of Public Health. / Vigilância de chikungunya no Brasil: desafios no contexto da Saúde Pública.

OBJECTIVE: to describe the challenges in implementing the chikungunya surveillance and prevention system in Brazil. METHODS: this was a descriptive study of suspected cases of the disease based on records held on the Notifiable Diseases Information System (Sinan) for the period 2014-2016. RESULTS: more than 100,000 probable chikungunya cases were notified in Brazil in this period, with the largest concentration in the Northeast states (83.3% between 2014 and 2015; 91.0% in 2016); Sinan provided an excellent opportunity for closing records of cases occurring between 2014 and 2015 (85%) and high completeness of obligatory variables. CONCLUSION: given the imminence of the introduction of chikungunya in Brazil in 2014, advance public health preparation took place in order to minimize its effects on society; implementation of the surveillance system improved collection of information regarding the disease, however many challenges can be seen in practice, in view of increasing case incidence. This requires greater handling capacity in this sector.

Optical properties and antiangiogenic activity of a chalcone derivate.

Chalcones and their derivatives exhibit numerous pharmacological activities such as antibacterial, antifungal, cytotoxic, antinociceptive and anti-inflammatory. Recently, they have been assessed aiming for novel application in nonlinear optics and in the treatment of immune diseases and cancers. In this study, we investigate the optical properties of synthetic chalcona 1E,4E-1-(4-chlorophenyl)-5-(2,6,6-trimethylcyclohexen-1-yl)penta-1,4-dien-3-one (CAB7ß) and its antiangiogenic potential using the chorioallantoic membrane (CAM) with the S180 sarcoma cell line. Experimental and theoretical results show intense absorption in the UVA-UVC region, which is associated with a π → π* transition with intramolecular charge transfer from the trimethyl-cyclohexen-1-yl ring to the chlorophenyl ring. Quantum chemical calculations of the first hyperpolarizability, accounting for both solvent and frequency dispersion effects, are in very good concordance with hyper-Rayleigh scattering measurements. In addition, two-photon absorption allowed band centered at 650 nm was observed. Concerning antiangiogenic activity, CAB7ß causes a significant reduction in the total number, junctions, length and caliber of blood vessels stimulated by S180 cells reducing the presence of blood vessels, inflammatory cells and others elements related to angiogenic process. It is found that CAB7ß is a versatile compound and a promising candidate for linear and nonlinear optical applications, in therapy against sarcoma and phototherapy.

Effect of physical exercise on the renal structures of ovariectomized female LDL knockout mice / Efecto del ejercicio físico sobre las estructuras renales de ratones hembras con LDL ovariectomizadas

SUMMARY: The reduction of ovarian function and a decrease in estrogen levels marked by menopause are related to increased susceptibility to develop dyslipidemia. These alterations in the lipid profile can have consequences in renal tissue and generate injuries that may progress to renal failure. The practice of physical activity is an important factor for the treatment and prevention of dyslipidemia and its consequences. The objective of this study is to observe the effects of physical exercise on the right kidney of ovariectomized female LDL knockout mice. Animals were submitted to moderate physical exercise, sacrificed, and the right kidney was removed for morphometric and stereological analysis. The results showed that dyslipidemia promoted a decrease in the areas of the corpuscle and renal glomerulus, in the volume density of light in both the proximal and distal convoluted tubules, and an increase in capsular space, particularly more marked in the proximal tubules. We also observed that physical exercise decreased the analyzed parameters. Our results suggest the association of physical training and dyslipidemia presents a tendency to reduce the dimensions of morphometric and stereological parameters of the kidney. These changes may be related to metabolic and physiological adaptation of renal tissue during physical exercise.

RESUMEN: La reducción de la función ovárica y una disminución en los niveles de estrógeno, marcados por la menopausia, se relacionan con una mayor susceptibilidad a desarrollar dislipidemia. Estas alteraciones en el perfil lipídico pueden tener consecuencias en el tejido renal y generar lesiones que pueden progresar a insuficiencia renal. La práctica de la actividad física es un factor importante para el tratamiento y la prevención de la dislipidemia y sus consecuencias. El objetivo de este estudio fue observar los efectos del ejercicio físico en el riñón derecho de ratones hembras con LDL ovariectomizados. Los animales fueron sometidos a ejercicio físico moderado, se sacrificaron y se extrajo el riñón derecho para el análisis morfométrico y estereológico. Los resultados mostraron que la dislipidemia promovió una disminución en las áreas del corpúsculo y el glomérulo renal, en la densidad volumétrica de la luz en los túbulos contorneados proximales y distales, y un aumento en el espacio capsular, particularmente más marcado en los túbulos proximales. También observamos que el ejercicio físico disminuyó los parámetros analizados. Nuestros resultados sugieren que la asociación del entrenamiento físico y la dislipidemia presentan una tendencia a reducir las dimensiones de los parámetros morfométricos y estereológicos del riñón. Estos cambios pueden estar relacionados con la adaptación metabólica y fisiológica del tejido renal durante el ejercicio físico.

Effects of moderate exercise on biochemical, morphological, and physiological parameters of the pancreas of female mice with estrogen deprivation and dyslipidemia.

Menopausal women are at high risk of developing heart disease. However, physical exercise practice can reverse this scenario. We evaluated the biochemical, morphological, and physiological effects of moderate aerobic physical exercise on the pancreas of knockout mice for LDL receptor with estrogen deprivation by ovariectomy. Animals were divided into six groups (n = 5): sedentary non-ovariectomized control; sedentary ovariectomized control; trained ovariectomized control; sedentary non-ovariectomized LDL-R knockout; sedentary ovariectomized LDL-R knockout; and trained ovariectomized LDL-R knockout. Physical exercise practice promoted improvement in biometric and biochemical parameters analyzed, with reduction of visceral adipose tissue and VLDL, triglycerides, total cholesterol, and blood glucose levels. In addition, physical exercise practice altered the morphology of pancreatic islets and improved their response to the effects of menopause. Thus, physical exercise practice was fundamental to minimize the effects of dyslipidemia associated with ovariectomy in the pancreatic tissue of LDL-R knockout animals, contributing to reduce the risk of developing cardiac diseases in the menopause period.