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1.
Anim Reprod ; 20(3): e20220084, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37795200

RESUMO

The aim of this study was to evaluate the oxidative stress in ovaries and corpus luteum (CL) of Bos taurus indicus females and the oxidant effect of CL in ovarian tissues in regions near, intermediate, or distant from it. Ovaries (n=12) of Nelore heifers (n=6) were collected from a slaughterhouse and fragmented. Experiment 1, each ovary was obtained from three fragments, resulting in 18 fragments of ovaries with CL (OV+CL) and another 18 fragments of ovaries without CL (OV-CL). Three fragments were generated from CL, totaling 18 CL fragments. In experiment 2, the ovarian fragments were removed from specific regions near, intermediate, or distant from the CL. All the fragments were placed in Eppendorf-type microtubes (1 mL), kept in a thermal container at 4 ºC, and then stored in a -80 ºC freezer for analysis of oxidative stress (TBARS and NBT) and antioxidant potential (FRAP and ABTS). In the antioxidant activity analysis, luteal tissues showed more antioxidant activity than ovarian tissue (FRAP = P < 0.0001; ABTS = P < 0.02). In the oxidative stress analysis, CL had lower levels of reactive oxygen species (ROS; TBARS = P < 0.03; NBT = P < 0.0001) than ovarian tissues. There was no difference in antioxidant activity and oxidative stress between the fragments obtained from different regions (OV+CL versus OV-CL; P > 0.05). The presence of CL in the ovaries of Bos taurus indicus females did not influence the oxidative stress or antioxidant potential of the gonad. Thus, the removal of ovarian fragments with or without the presence of CL indicates that biotechnologies such as in vitro follicle cultivation is possible.

2.
Nitric Oxide ; 134-135: 49-60, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-37054808

RESUMO

INTRODUCTION: Available studies have shown the involvement of nitric oxide (NO) in the processes that lead to neurodegeneration in Parkinson's disease (PD). Also, the use of inhibitors of the inducible isoform of NO-synthase (iNOS) promotes neuroprotection and attenuates dopamine (DA) loss in experimental models of Parkinsonism. In addition, NO also appears to be involved in cardiovascular changes in 6-hydroxydopamine (6-OHDA)-induced Parkinsonism. The current study aimed to evaluate the effects of iNOS inhibition on cardiovascular and autonomic function in animals that were subjected to Parkinsonism by the administration of 6-OHDA. MATERIALS AND METHODS: The animals underwent stereotaxic surgery for bilateral microinfusion of the neurotoxin 6-OHDA (6 mg/mL in 0.2% ascorbic acid in sterile saline solution) or vehicle solution for the Sham group. From the day of stereotaxis until the day of femoral artery catheterization, the animals were treated with the iNOS inhibitor, S-methylisothiourea (SMT; 10 mg/kg; i. p.) or saline solution (0.9%; i. p.) for 7 days. The animals were divided into four groups: Sham-Saline, Sham-SMT, 6-OHDA-Saline, and 6-OHDA-SMT. Subsequent analyses were performed on these four groups. After 6 days, they underwent catheterization of the femoral artery, and 24 h later, mean arterial pressure (MAP) and heart rate (HR) were recorded. Another group of animals (the 6-OHDA and Sham groups) was assessed for aortic vascular reactivity after 7 days of bilateral infusion of 6-OHDA or vehicle, in which cumulative concentration-effect curves (CCEC) were made for phenylephrine (Phenyl), acetylcholine and sodium nitroprusside (NPS). Also, CCEC in the presence of Nw-nitro-arginine-methyl-ester (l-NAME) (10-5 M), SMT (10-6 M), and indomethacin (10-5 M) blockers were made. RESULTS: The effectiveness of the 6-OHDA lesion was confirmed with the reduction of DA in 6-OHDA animals. However, treatment with SMT could not reverse the loss of DA. Concerning the baseline parameters, SBP and MAP values were lower in 6-OHDA animals compared to their Sham control, with no effect of treatment with SMT. In the analysis of SBP variability, a decrease in variance, the VLFabs component, and the LFabs component were observed in the 6-OHDA groups when compared to their controls, regardless of treatment with SMT. It was also observed that intravenous injections of SMT resulted in an increase in BP and a decrease in HR. However, the response was not different between the Sham and 6-OHDA groups. In vascular function, there was a hyporeactivity to Phenyl in the 6-OHDA group, and when investigating the mechanisms of this hyporeactivity, it was seen that the Rmax to Phenyl increased with incubation with SMT, indicating that iNOS could be involved in the vascular hyporeactivity of animals with Parkinsonism. CONCLUSION: Thus, the set of results presented in this study suggests that part of the cardiovascular dysfunction in animals subjected to 6-OHDA Parkinsonism may be peripheral and involve the participation of endothelial iNOS.


Assuntos
Sistema Cardiovascular , Transtornos Parkinsonianos , Animais , Masculino , Ratos , Dopamina , Inibidores Enzimáticos/farmacologia , NG-Nitroarginina Metil Éster/farmacologia , Oxidopamina/farmacologia , Transtornos Parkinsonianos/induzido quimicamente , Transtornos Parkinsonianos/tratamento farmacológico , Fenilefrina , Ratos Wistar , Solução Salina
4.
J Dev Orig Health Dis ; 14(2): 286-293, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36336997

RESUMO

Malathion is an insecticide that is used to control arboviruses and agricultural pests. Adolescents that are exposed to this insecticide are the most vulnerable as they are in the critical period of postnatal sexual development. This study aimed to evaluate whether malathion damage can affect sperm function and its respective mechanisms when adolescents are exposed during postnatal sexual development. Twenty-four male Wistar rats (PND 25) were divided into three experimental groups and treated daily for 40 d: control group (saline 0.9%), 10 mg/kg (M10 group), or 50 mg/kg (M50 group) of malathion. At PND 65, the rats were anesthetized and euthanized. Testicles were collected for the evaluation of gene expression. Sperm cells from the epididymis were used for evaluation of the oxidative profile or spermatic function. Data showed that a lower dose of malathion downregulated the gene expression of androgen receptors and testosterone converter enzyme 17-ß-HSD in the testis. The acrosomal integrity of sperm cells was compromised in the M50 group, but not the M10 group. The mitochondrial activity was not impaired by exposure. Finally, although no alterations in malondialdehyde and glutathione levels were observed, malathion, at both doses, increased antioxidant enzyme catalase activity and, at a higher dose, superoxide dismutase activity. The present study showed that low doses of malathion considered to be inoffensive are capable of impairing sperm quality and function through the downregulation of testicular genic expression of AR enzyme 17-ß-HSD and can damage the spermatic antioxidant profile during critical periods of development.


Assuntos
Inseticidas , Testículo , Animais , Masculino , Ratos , Antioxidantes , Expressão Gênica , Inseticidas/toxicidade , Inseticidas/metabolismo , Malation/toxicidade , Malation/metabolismo , Ratos Wistar , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Sêmen/metabolismo , Espermatozoides , Testículo/metabolismo , 17-Hidroxiesteroide Desidrogenases
5.
Naunyn Schmiedebergs Arch Pharmacol ; 395(10): 1269-1282, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35852551

RESUMO

Type 1 diabetes mellitus (T1DM) is a chronic disease related to a persistent inflammatory process reaching the central nervous system, which leads to psychiatric comorbidities such as depression and anxiety. The search for new therapeutic agents effective in alleviating the psychiatric condition associated with T1DM becomes critical. Using an animal model of T1DM, we aimed to evaluate the effect of a specific specialized pro-resolving lipid mediator Resolvin D5 (RvD5), in preventing behaviors related to depression and anxiety, investigating its influence on inflammasome in interleukin (IL)-1ß in the hippocampus and prefrontal cortex. After experimental T1DM induction with streptozotocin (60 mg/kg, i.p.), these animals were treated for 23 days and randomly divided into 6 subgroups according to the treatment: vehicle (VEH), the antidepressant Fluoxetine (FLX; 10 mg/kg), the nonsteroidal anti-inflammatory Ibuprofen (IBU; 30 mg/kg) or Resolvin D5 (RvD5; 1 3, or 10 ng/animal). As a control group for the experimental-T1DM condition, a group of normoglycemic animals treated with VEH underwent the same behavioral tests: elevated plus maze, open field, and modified forced swimming tests. In the end, hippocampus and prefrontal cortex samples were processed to analyze the pro-inflammatory cytokine IL-1ß levels. Our data showed that RvD5 treatment prevented the more pronounced anxious-like and reduced the depressive-like behaviors of experimental-T1DM animals and significantly improved the plasma glucose levels. Additionally, RvD5 treatment prevented the increased level of pro-inflammatory cytokine IL-1ß in the hippocampus and prefrontal cortex of experimental-T1DM rats. To conclude, RvD5 presents a preventive therapeutic potential in impairing the development of the emotional complications resulting from T1DM. This potential may be related to its protective profile, as demonstrated in this study by its pro-resolutive action on neuroinflammation in the hippocampus and prefrontal cortex.


Assuntos
Diabetes Mellitus Tipo 1 , Animais , Ansiedade/tratamento farmacológico , Comportamento Animal , Citocinas , Depressão/tratamento farmacológico , Depressão/etiologia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Modelos Animais de Doenças , Ácidos Docosa-Hexaenoicos , Hipocampo , Ratos
6.
J Agric Food Chem ; 70(25): 7644-7652, 2022 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-35675570

RESUMO

Poly(epsilon-caprolactone) nanoparticles are an efficient carrier system for atrazine. However, there is a gap regarding the effects of nanoencapsulation on herbicide-plant interactions. Here, we evaluate the fate and photosystem II inhibition of nano and commercial atrazine in hydroponically grown mustard (Brassica juncea) plants whose roots were exposed to the formulations. In addition, to quantify the endogenous levels of atrazine in plant organs, we measured the inhibition of photosystem II activity by both formulations. Moreover, the fluorescently labeled nanoatrazine was tracked in plant tissues using confocal microscopy. The nanoencapsulation induced greater inhibition of photosystem II activity as well as higher accumulation of atrazine in roots and leaves. The nanoparticles were quickly absorbed by the roots, being detected in the vascular tissues and the leaves. Overall, these results provide insights into the mechanisms involved in the enhanced preemergent herbicidal activity of nanoatrazine against target plants.


Assuntos
Atrazina , Herbicidas , Atrazina/farmacologia , Herbicidas/farmacologia , Mostardeira , Complexo de Proteína do Fotossistema II , Raízes de Plantas
7.
Microbes Infect ; 24(5): 104971, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35341976

RESUMO

Owing to the serious adverse effects caused by pyrimethamine and sulfadiazine, the drugs commonly used to treat toxoplasmosis, there is a need for treatment alternatives for this disease. Nanotechnology has enabled significant advances toward this goal. This study was conducted to evaluate the activity of biogenic silver nanoparticles (AgNp-Bio) in RAW 264.7 murine macrophages infected with the RH strain of Toxoplasma gondii. The macrophages were infected with T. gondii tachyzoites and then treated with various concentrations of AgNp-Bio. The cells were evaluated by microscopy, and culture supernatants were collected for ELISA determination of their cytokine concentration. Treatment with 6 µM AgNp-Bio reduced the infection and parasite load in infected RAW 264.7 macrophages without being toxic to the cells. The treatment also induced the synthesis of reactive oxygen species and tumor necrosis factor-alpha (both pro-inflammatory mediators), which resulted in ultrastructural changes in the tachyzoites and their intramacrophagic destruction. Our findings suggest that AgNp-Bio affect T. gondii tachyzoites by activating microbicidal and pro-inflammatory mechanisms and may be a potential alternative treatment for toxoplasmosis.


Assuntos
Macrófagos , Nanopartículas Metálicas , Prata , Toxoplasmose , Animais , Proliferação de Células , Macrófagos/efeitos dos fármacos , Macrófagos/parasitologia , Camundongos , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , Prata/farmacologia , Toxoplasma , Toxoplasmose/tratamento farmacológico , Fator de Necrose Tumoral alfa/metabolismo
8.
Life Sci ; 295: 120405, 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35181311

RESUMO

AIMS: The rostral ventrolateral medulla (RVLM) is the main sympathetic output of the central nervous system to control blood pressure. Reportedly, reactive oxygen species (ROS) can increase arterial pressure, leading to hypertension. As ROS increase the sympathetic tone in RVLM and obese animals present grater oxidative stress, it would be important to note this relationship. MAIN METHODS: Therefore, we evaluated the systemic and central effects (in the RVLM) of vitamin C (vit C, an antioxidant) on the redox balance and cardiovascular and autonomic profiles in hyperadipose male rats. We also evaluated the neurotransmission by L-glutamate (L-glu) and vit C in the RVLM of awake hyperadipose rats. KEY FINDINGS: Our study confirmed that hyperadipose rats were hypertensive and tachycardic, presented increased sympathetic and decreased parasympathetic modulation of the heart, and had increased plasma lipoperoxidation compared with the control rats (CTR). Oral vitamin C treatment reverted cardiovascular, autonomic, and plasma redox dysfunction. Hyperadipose rats presented a higher blood pressure increase after L-glu microinjection and a lower response to vit C in the RVLM compared with the CTR group. Biochemical analysis of redox balance in RVLM punches showed that hyperadipose rats have increased NBT and T-BARS, and after treatment with vit C, the oxidative profile decreased. The antioxidative activity of vit C reduced the amount of ROS in the RVLM area that might have resulted in lowered blood pressure and sympathetic modulation. SIGNIFICANCE: Our data suggest central and peripheral benefits of vit C treatment on cardiovascular, autonomic, and oxidative dysfunctions in hyperadipose animals.


Assuntos
Ácido Ascórbico/farmacologia , Hipertensão/tratamento farmacológico , Bulbo/metabolismo , Animais , Antioxidantes/farmacologia , Sistema Nervoso Autônomo/fisiopatologia , Pressão Sanguínea/efeitos dos fármacos , Sistema Cardiovascular/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Hipertensão/fisiopatologia , Masculino , Bulbo/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/farmacologia , Superóxido Dismutase/metabolismo , Sistema Nervoso Simpático/efeitos dos fármacos , Sistema Nervoso Simpático/metabolismo
9.
Food Chem ; 368: 130817, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34411863

RESUMO

Novel microcapsules containing grape peel by-product extract were obtained. In this pursuit, complex coacervation of casein/pectin bioconjugate and spray-drying were combined. We have investigated the role of the dispersion feed rate (FR), drying air inlet temperature (IT) and drying air flow rate (AR) in the drying yield, microencapsulation efficiency, total polyphenols and anthocyanins contents, antioxidant activity, and morphology of the products. Also, the first-order degradation kinetics of the phytochemicals for both the extract and dried microcapsules was assessed and compared. The loss on the phytochemicals during spray-drying was attenuated in up to 88%, and the IT was the main factor affecting the particle properties. The polyphenols on the extract interacted with the polymers, influencing the assemble of the bioconjugate and the particle's features. Such microencapsulation strategy enhanced the thermal stability of the phytochemicals and rendered biocompatible and biodegradable products of which the nutraceutical and cosmeceutical application may have potential.


Assuntos
Vitis , Antocianinas , Cápsulas , Caseínas , Composição de Medicamentos , Pectinas
10.
Reprod Sci ; 29(1): 277-290, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34494235

RESUMO

The hyperhomocysteinemia (HHcy) is toxic to the cells and associated with several diseases. Clinical studies have shown changes in plasma concentrations of Hcy after physical exercise. This study aimed to assess the effect of HHcy on testis, epididymis and sperm quality and to investigate whether voluntary exercise training protects this system against damage caused by HHcy in Swiss mice. In this study, 48 mice were randomly distributed in the control, HHcy, physical exercise, and HHcy combined with physical exercise groups. HHcy was induced by daily administration of dl-homocysteine thiolactone via gavage throughout the experimental period. Physical exercise was performed through voluntary running on the exercise wheels. The plasma concentrations of homocysteine (Hcy) and testosterone were determined. The testes and epididymis were used to assess the sperm count, histopathology, lipoperoxidation, cytokine levels, testicular cholesterol, myeloperoxidase, and catalase activity. Spermatozoa were analyzed for morphology, acrosome integrity, mitochondrial activity, and motility. In the testes, HHcy increased the number of abnormal seminiferous tubules, reduced the tubular diameter and the height of the germinal epithelium. In the epididymis, there was tissue remodeling in the head region. Ultimately, voluntary physical exercise training reduced plasma Hcy concentration but did not attenuate HHcy-induced testicular and epididymal disturbances.


Assuntos
Epididimo/fisiopatologia , Hiper-Homocisteinemia/terapia , Condicionamento Físico Animal/fisiologia , Testículo/fisiopatologia , Animais , Catalase/sangue , Epididimo/metabolismo , Homocisteína/sangue , Hiper-Homocisteinemia/sangue , Hiper-Homocisteinemia/fisiopatologia , Masculino , Camundongos , Estresse Oxidativo/fisiologia , Testículo/metabolismo , Testosterona/sangue , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
11.
In Vitro Cell Dev Biol Anim ; 57(9): 856-864, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34748153

RESUMO

We evaluated the effect of quercetin on the in vitro culture of bovine ovarian fragments in relation to morphology, development, and oxidative stress. Ovaries (n = 12) from Nelore heifers (n = 6) were used. Each pair of ovaries was divided into nine fragments, and one fragment from each animal was fixed in Bouin solution for 24 h (histology control) or frozen (- 80°C; control for oxidative stress). Other ovarian fragments (n = 8) were distributed into concentrations of 0, 10, 25, and 50 µg/mL of quercetin added to the culture medium for 5 or 10 d. Data were analyzed by chi-square test or ANOVA followed by Tukey's test (P < 0.05). Treatment with 25 µg/mL quercetin resulted in the highest proportion of total intact follicles for 5 (67.3%) and 10 d (57.1%); the concentration of 25 µg/mL also presented the best proportion of developing follicles for 5 d (68.7%) and 10 d (62.8%). Treatment with 25 µg/mL quercetin resulted in significant ferric reduction for 10 d of culture, but not for 5 d. No difference (P > 0.1) was observed in the production of reactive oxygen species or in the oxidative degradation of lipids between treatments and non-cultivated controls. Treatment with 25 µg/mL quercetin preserved the morphological integrity of the developing follicles for 5 and 10 d of culture, in addition to promoting the best antioxidant potential after 10 d of culture in bovine ovarian fragments.


Assuntos
Antioxidantes/farmacologia , Folículo Ovariano/crescimento & desenvolvimento , Ovário/efeitos dos fármacos , Quercetina/farmacologia , Animais , Bovinos , Técnicas de Cultura de Células/métodos , Meios de Cultura/química , Meios de Cultura/farmacologia , Feminino , Técnicas de Cultura de Órgãos , Folículo Ovariano/efeitos dos fármacos , Ovário/fisiologia , Estresse Oxidativo/efeitos dos fármacos , Tiobarbitúricos/metabolismo
12.
Front Microbiol ; 12: 710359, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34566915

RESUMO

Zika virus (ZIKV) is an arthropod-born virus that is mainly transmitted to humans by mosquitoes of the genus Aedes spp. Since its first isolation in 1947, only a few human cases had been described until large outbreaks occurred on Yap Island (2007), French Polynesia (2013), and Brazil (2015). Most ZIKV-infected individuals are asymptomatic or present with a self-limiting disease and nonspecific symptoms such as fever, myalgia, and headache. However, in French Polynesia and Brazil, ZIKV outbreaks led to the diagnosis of congenital malformations and microcephaly in newborns and Guillain-Barré syndrome (GBS) in adults. These new clinical presentations raised concern from public health authorities and highlighted the need for anti-Zika treatments and vaccines to control the neurological damage caused by the virus. Despite many efforts in the search for an effective treatment, neither vaccines nor antiviral drugs have become available to control ZIKV infection and/or replication. Flavonoids, a class of natural compounds that are well-known for possessing several biological properties, have shown activity against different viruses. Additionally, the use of flavonoids in some countries as food supplements indicates that these molecules are nontoxic to humans. Thus, here, we summarize knowledge on the use of flavonoids as a source of anti-ZIKV molecules and discuss the gaps and challenges in this area before these compounds can be considered for further preclinical and clinical trials.

14.
Mycopathologia ; 186(1): 81-91, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33151458

RESUMO

BACKGROUND: Candida tropicalis is an important human pathogen that can undergo multiple forms of phenotypic switching. AIM: We aimed to evaluate the effect of phenotypic switching on the adhesion ability of C. tropicalis. METHODS: C. tropicalis morphotypes included parental phenotypes (clinical isolates) and switch phenotypes (crepe, revertant of crepe-CR, rough, revertant of rough-RR, irregular center and revertant of irregular center-ICR). Adhesion to polystyrene and HeLa cells was determined by crystal violet assay. The percentage of HeLa cells with adhered yeasts and the number of adhered yeasts per HeLa cell were determined by light microscopy. Filamentation among adhered cells was assessed by direct counting. RESULTS: On polystyrene, 60% of the switch strains showed difference (p < 0.05) on adhesion ability compared to their parental counterpart strains, and altered thickness of adhered cells layers. Filamentation was increased among adhered cells of the switched strains compared to parental strains. A positive correlation was observed between adhesion on polystyrene and filamentation for morphotypes of the system 49.07. The majority of the switched strains showed higher adhesion capability to HeLa cells in comparison to the adherence of the clinical strains. All revertant strains showed a higher number of yeast cells per HeLa cell compared to their variant counterparts (p < 0.05), with exception of the ICR. CONCLUSIONS: Our findings indicate that switching events in C. tropicalis affect adhesion and filamentation of adhered cells on polystyrene and HeLa cells. The rise of switch strains with increased adhesion ability may contribute to the success of infection associated with C. tropicalis.


Assuntos
Candida tropicalis , Poliestirenos , Biofilmes , Adesão Celular , Células HeLa , Humanos , Fenótipo
15.
J Drug Target ; 28(10): 1110-1123, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32546016

RESUMO

The use of compounds from natural or synthetic sources and nanotechnology may represent an alternative to develop new drugs for the leishmaniasis treatment. DETC is an inhibitor of the SOD1 enzyme, which leads to increased ROS production, important for the elimination of Leishmania. Thus, our objective was to assess the leishmanicidal in vitro effect of free Diethydithiocarbamate (DETC) and DETC loaded in beeswax-copaiba oil nanoparticles (DETC-Beeswax-CO Nps) on L. amazonensis forms and elucidate the possible mechanisms involved in the parasite death. DETC-Beeswax-CO Nps presented size below 200 nm, spherical morphology, negative zeta potential, and high encapsulation efficiency. Free DETC reduced the viability of promastigotes and increase ROS production, lower the mitochondrial membrane potential, cause phosphatidylserine exposure, and enhance plasma membrane permeability, in addition to promoting morphological changes in the parasite. Free DETC proved toxic in the assessment of toxicity to murine macrophages, however, the encapsulation of this compound was able to reduce these toxic effects on macrophages. DETC-Beeswax-CO Nps exerted anti-amastigote effect by enhancing the production of ROS, superoxide anion, TNF-α, IL-6, and reduced IL-10 in macrophages. Therefore, free DETC induces antipromastigote effect by apoptosis-like; and DETC-Beeswax-CO Nps exerted anti-leishmanial effect due to pro-oxidant and pro-inflammatory response.


Assuntos
Ditiocarb/farmacologia , Leishmania/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Nanopartículas/química , Espécies Reativas de Oxigênio/metabolismo , Animais , Apoptose/efeitos dos fármacos , Ditiocarb/administração & dosagem , Camundongos Endogâmicos BALB C , Preparações de Plantas/química , Propriedades de Superfície , Ceras/química
16.
Reprod Toxicol ; 96: 17-26, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32479887

RESUMO

Malathion is an organophosphate insecticide used in agriculture and for controlling vector-borne diseases such as Zika. Humans can be exposed to malathion by means of ingestion of contaminated food. The juvenile and peripubertal periods are a large window of vulnerability to the action of toxic agents. The aim of the present study was to evaluate the effects of low doses of malathion during the development of testes in the juvenile and peripubertal periods in rats. For this purpose, 45 male Wistar rats (postnatal day (PND) 25) were assigned to 3 experimental groups and treated for 40 days. The animals were exposed daily to malathion 10 mg/kg (M10 group) or 50 mg/kg (M50 group) diluted in 0.9 % saline via gavage. The control group received only the vehicle. On the 40th experimental day, the rats were anaesthetized and euthanized. The blood was collected for determination of testosterone concentration. The testes were removed and weighed. Spermatozoa from the vas deferens were used for sperm morphological analysis. The testes were used for evaluation of sperm count and oxidative stress status to determine the inflammatory profile and analysis of tissue constitution. The results showed that both malathion doses reduced the sperm count and increased the number of abnormal sperms. Furthermore, both doses altered the spermatogenetic process, delayed spermiogenesis, reduced the Leydig and Sertoli cell number and increased the thickness of tunica albuginea. The M10 group presented increased IL-10 levels and reduced GSH levels. These parameters did not change in the M50 group. However, the M50 group showed an increase in the number of abnormal seminiferous tubules, a decrease in plasma testosterone concentration and an increase in lipid peroxidation in the testes. In conclusion, the exposure to low doses of malathion during juvenile and peripubertal development resulted in testicular toxicity and compromised the testicular morphology and function.


Assuntos
Inseticidas/toxicidade , Malation/toxicidade , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Citocinas/metabolismo , Glutationa/metabolismo , Masculino , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/metabolismo , Ratos Wistar , Maturidade Sexual/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Espermatozoides/anormalidades , Espermatozoides/fisiologia , Testículo/metabolismo , Testículo/patologia , Testosterona/sangue
17.
Artigo em Inglês | MEDLINE | ID: mdl-32366719

RESUMO

Chagas disease, caused by the protozoan Trypanosoma cruzi, is one of the main causes of death due to cardiomyopathy and heart failure in Latin American countries. The treatment of Chagas disease is directed at eliminating the parasite, decreasing the probability of cardiomyopathy and disrupting the disease transmission cycle. Benznidazole (BZ) and nifurtimox (Nfx) are recognized as effective drugs for the treatment of Chagas disease by the World Health Organization, but both have high toxicity and limited efficacy, especially in the chronic disease phase. At low doses, aspirin (ASA) has been reported to protect against T. cruzi infection. We evaluated the effectiveness of BZ in combination with ASA at low doses during the acute disease phase and evaluated cardiovascular aspects and cardiac lesions in the chronic phase. ASA treatment prevented the cardiovascular dysfunction (hypertension and tachycardia) and typical cardiac lesions. Moreover, BZ+ASA-treated mice had a smaller cardiac fibrotic area than BZ-treated mice. These results were associated with an increase in numbers of eosinophils and reticulocytes and levels of nitric oxide in the plasma and cardiac tissue of ASA-treated mice relative to respective controls. These effects of ASA and BZ+ASA in chronically infected mice were inhibited by pretreatment with the lipoxin A4 (LXA4) receptor antagonist Boc-2, indicating that the protective effects of ASA are mediated by ASA-triggered lipoxin. These results emphasize the importance of exploring new drug combinations for treatments of the acute phase of Chagas disease that are beneficial for patients with chronic disease.


Assuntos
Doença de Chagas , Nitroimidazóis , Tripanossomicidas , Trypanosoma cruzi , Animais , Aspirina/uso terapêutico , Doença de Chagas/tratamento farmacológico , Combinação de Medicamentos , Humanos , Camundongos , Nitroimidazóis/farmacologia , Nitroimidazóis/uso terapêutico , Tripanossomicidas/uso terapêutico
18.
Neurotoxicology ; 77: 193-204, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32007490

RESUMO

Given the well-known antioxidant and neuroprotective properties of quercetin, the aim of this work was to evaluate the effects of quercetin stabilized by microencapsulation at two doses (10 mg kg-1 and 100 mg kg-1) on the oxidative/antioxidant status, number and morphological features of ICC, nitrergic neurons and M2-like macrophages in jejunum of diabetic rats. The rats were randomly distributed into six groups: normoglycemic control (N), diabetic control (D) and either normoglycemic or diabetic groups treated with quercetin-loaded microcapsules at a dose of 10 mg kg-1 (NQ10 and DQ10, respectively) or 100 mg kg-1 (NQ100 and DQ100, respectively). After 60 days, the jejunum was collected. Whole mounts were immunostained for Ano1, nNOS and CD206, and oxidative stress levels and total antioxidant capacity of the jejunum were measured. Diabetes led to a loss of ICC and nitrergic neurons, but increased numbers of M2-like macrophages and elevated levels of oxidative stress were seen in diabetic animals. High-dose administration of quercetin (100 mg kg-1) further aggravated the diabetic condition (DQ100) but this treatment resulted in harmful effects on healthy rats (NQ100), pointing to a pro-oxidant activity. However, low-dose administration of quercetin (10 mg kg-1) gave rise to antioxidant and protective effects on ICC, nNOS, macrophages and oxidative/antioxidant status in DQ100, but NQ100 displayed infrequent negative outcomes in normoglycemic animals. Microencapsulation of the quercetin may become promising alternatives to reduce diabetes-induced oxidative stress but antioxidant therapies should be careful used under healthy status to avoid toxic effects.


Assuntos
Antioxidantes/administração & dosagem , Diabetes Mellitus Tipo 1/metabolismo , Jejuno/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Neurônios Nitrérgicos/efeitos dos fármacos , Quercetina/administração & dosagem , Telócitos/efeitos dos fármacos , Animais , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 1/induzido quimicamente , Composição de Medicamentos , Jejuno/metabolismo , Macrófagos/metabolismo , Masculino , Plexo Mientérico/efeitos dos fármacos , Plexo Mientérico/metabolismo , Neurônios Nitrérgicos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Estreptozocina/administração & dosagem , Telócitos/metabolismo
19.
Eur Arch Otorhinolaryngol ; 277(2): 483-492, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31734722

RESUMO

PURPOSE: There is no standardized approach for preserving olfactory function in the side of the nose where biopsy of the olfactory epithelium (OE) is performed. Moreover, a gold standard technique for obtaining human OE in vivo is still lacking. We determined the efficacy of obtaining good-quality OE specimens suitable for pathological analysis from the lower half of the superior turbinate and verified the safety of this procedure in maintaining bilateral and unilateral olfactory function. METHODS: In 21 individuals without olfactory complaints and who had undergone septoplasty and inferior turbinectomy OE biopsy was made during septoplasty. Olfactory function, both unilateral and bilateral, was assessed using the University of Pennsylvania Smell Identification Test (UPSIT) before and 1 month after the procedure. Specimens were marked with the olfactory marker protein for confirmation of OE presence. RESULTS: Ninety percent of the samples contained OE, although clear histological characterization was possible from only 62%. There was no deterioration of UPSIT scores either bilaterally or unilaterally on the side of the biopsy. Patients also maintained the ability to identify individual odorants. CONCLUSION: Biopsies of the lower half of the superior turbinate do not affect olfactory function and show strong efficacy in yielding OE tissue and moderate efficacy for yielding tissue appropriate for morphological analysis. Future studies are needed to assess the safety of this procedure in other OE regions.


Assuntos
Mucosa Olfatória/fisiologia , Olfato/fisiologia , Conchas Nasais/fisiologia , Adolescente , Adulto , Biópsia/normas , Feminino , Humanos , Masculino , Odorantes , Mucosa Olfatória/anatomia & histologia , Mucosa Olfatória/cirurgia , Resultado do Tratamento , Conchas Nasais/anatomia & histologia , Conchas Nasais/cirurgia , Adulto Jovem
20.
Sci Rep ; 9(1): 18885, 2019 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-31827186

RESUMO

We evaluated the influence of metabolic syndrome (MS) on acute Trypanosoma cruzi infection. Obese Swiss mice, 70 days of age, were subjected to intraperitoneal infection with 5 × 102 trypomastigotes of the Y strain. Cardiovascular, oxidative, inflammatory, and metabolic parameters were evaluated in infected and non-infected mice. We observed higher parasitaemia in the infected obese group (IOG) than in the infected control group (ICG) 13 and 15 days post-infection. All IOG animals died by 19 days post-infection (dpi), whereas 87.5% of the ICG survived to 30 days. Increased plasma nitrite levels in adipose tissue and the aorta were observed in the IOG. Higher INF-γ and MCP-1 concentrations and lower IL-10 concentrations were observed in the IOG compared to those in the ICG. Decreased insulin sensitivity was observed in obese animals, which was accentuated after infection. Higher parasitic loads were found in adipose and hepatic tissue, and increases in oxidative stress in cardiac, hepatic, and adipose tissues were characteristics of the IOG group. Thus, MS exacerbates experimental Chagas disease, resulting in greater damage and decreased survival in infected animals, and might be a warning sign that MS can influence other pathologies.


Assuntos
Tecido Adiposo/metabolismo , Doença de Chagas/metabolismo , Inflamação/metabolismo , Fígado/metabolismo , Síndrome Metabólica/metabolismo , Miocárdio/metabolismo , Estresse Oxidativo/fisiologia , Tecido Adiposo/patologia , Animais , Doença de Chagas/complicações , Doença de Chagas/patologia , Citocinas/sangue , Modelos Animais de Doenças , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Inflamação/complicações , Inflamação/patologia , Resistência à Insulina/fisiologia , Fígado/patologia , Masculino , Síndrome Metabólica/complicações , Síndrome Metabólica/patologia , Camundongos , Miocárdio/patologia , Trypanosoma cruzi
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