Curcumin and quercetin co-encapsulated in nanoemulsions for nasal administration: A promising therapeutic and prophylactic treatment for viral respiratory infections.

One of the most frequent causes of respiratory infections are viruses. Viruses reaching the airways can be absorbed by the human body through the respiratory mucosa and mainly infect lung cells. Several viral infections are not yet curable, such as coronavirus-2 (SARS-CoV-2). Furthermore, the side effect of synthetic antiviral drugs and reduced efficacy against resistant variants have reinforced the search for alternative and effective treatment options, such as plant-derived antiviral molecules. Curcumin (CUR) and quercetin (QUE) are two natural compounds that have been widely studied for their health benefits, such as antiviral and anti-inflammatory activity. However, poor oral bioavailability limits the clinical applications of these natural compounds. In this work, nanoemulsions (NE) co-encapsulating CUR and QUE designed for nasal administration were developed as promising prophylactic and therapeutic treatments for viral respiratory infections. The NEs were prepared by high-pressure homogenization combined with the phase inversion temperature technique and evaluated for their physical and chemical characteristics. In vitro assays were performed to evaluate the nanoemulsion retention into the porcine nasal mucosa. In addition, the CUR and QUE-loaded NE antiviral activity was tested against a murine ß-COV, namely MHV-3. The results evidenced that CUR and QUE loaded NE had a particle size of 400 nm and retention in the porcine nasal mucosa. The antiviral activity of the NEs showed a percentage of inhibition of around 99 %, indicating that the developed NEs has interesting properties as a therapeutic and prophylactic treatment against viral respiratory infections.

Preclinical toxicological assessment of polydatin in zebrafish model.

Polydatin (3,4',5-trihydroxystilbene-3-ß-D-glucoside, piceid), a natural stilbenoid found in different plant sources, has gained increasing attention for its potential health benefits. However, prior to its widespread adoption in human therapeutics and consumer products, a comprehensive investigation of its toxicological effects is crucial. In this study, the toxicity of polydatin was investigated in a developmental toxicity test using zebrafish (Danio rerio) as a valuable model for preclinical assessments. We employed the Fish Embryo Test (FET test - OECD n°236) to investigate the effects of polydatin on survival, hatchability, development, and behavior of zebrafish embryo-larval stage. Remarkably, the results demonstrated that polydatin up to 435 µM showed no toxicity. Throughout the exposure period, zebrafish embryos exposed to polydatin exhibited normal development, with no significant mortality observed. Furthermore, hatching success and heartbeat rate were unaffected, and no morphological abnormalities were identified, signifying a lack of teratogenic effects and cardiotoxicity. Locomotion activity assessment revealed normal swimming patterns and response to stimuli, indicating no neurotoxic effects. Our study provides valuable insights into the toxicological profile of polydatin, suggesting that it may offer potential therapeutic benefits under a considerable concentration range. In addition, zebrafish model proves to be an efficient system for early-stage toxicological screening, guiding further investigations into the secure utilization of polydatin for human health and wellness.

Toward a Platform for the Treatment of Burns: An Assessment of Nanoemulsions vs. Nanostructured Lipid Carriers Loaded with Curcumin.

Curcumin is a highly promising substance for treating burns, owing to its anti-inflammatory, antioxidant, antimicrobial, and wound-healing properties. However, its therapeutic use is restricted due to its hydrophobic nature and low bioavailability. This study was conducted to address these limitations; it developed and tested two types of lipid nanocarriers, namely nanoemulsions (NE-CUR) and nanostructured lipid carriers (NLC-CUR) loaded with curcumin, and aimed to identify the most suitable nanocarrier for skin burn treatment. The study evaluated various parameters, including physicochemical characteristics, stability, encapsulation efficiency, release, skin permeation, retention, cell viability, and antimicrobial activity. The results showed that both nanocarriers showed adequate size (~200 nm), polydispersity index (~0.25), and zeta potential (~>-20 mV). They also showed good encapsulation efficiency (>90%) and remained stable for 120 days at different temperatures. In the release test, NE-CUR and NCL-CUR released 57.14% and 51.64% of curcumin, respectively, in 72 h. NE-CUR demonstrated better cutaneous permeation/retention in intact or scalded skin epidermis and dermis than NLC-CUR. The cell viability test showed no toxicity after treatment with NE-CUR and NLC-CUR up to 125 µg/mL. Regarding microbial activity assays, free curcumin has activity against P. aeruginosa, reducing bacterial growth by 75% in 3 h. NE-CUR inhibited bacterial growth by 65% after 24 h, and the association with gentamicin had favorable results, while NLC-CUR showed a lower inhibition. The results demonstrated that NE-CUR is probably the most promising nanocarrier for treating burns.

Beneficial effects of mate-herb, Ilex paraguariensis St. Hil. against potassium dichromate-induced oxidative stress and nephrotoxicity.

Chimarrão is a typical beverage made from the infusion of dried and ground leaves and stems of Ilex paraguariensis (popularly known as Yerba mate or mate herb) which is widely consumed in parts of South America. The aim of this study was to examine the effects of the chimarrão against nephrotoxicity and oxidative stress induced by the potassium dichromate (PD) salt in male Wistar rats. The experiment lasted 17 days, and in the first 15 days animals ingested a chimarrão infusion or control drinking water and then submitted to an intraperitoneal injection (15 mg/kg) of PD (or saline solution) and euthanized after 48 hr at which time animals still received infusion or drinking water. Blood plasma and 24 hr-urine samples were collected to measure creatinine levels as an estimate of glomerular filtration rate (GFR). Concomitantly oxidative stress was determined in the kidneys as evidenced by levels of carbonyl groups, malondialdehyde (MDA) and antioxidant capacity against peroxyl radicals. Potassium dichromate induced oxidative stress in the kidneys and reduced GFR. Treatment with chimarrão during the 15 days prior to PD injection reduced PD salt-mediated oxidative stress. Further, treatment with post-injection chimarrão to PD-administered rats improved the GFR. Our findings support that the use of the chimarrão beverage may be considered as an important nephroprotective substance.

Human health risk assessment of air pollutants in the largest coal mining area in Brazil.

The Candiota region, located in the extreme south of Brazil, has the largest mineral coal deposit in the country, and this activity is capable of releasing pollutants in which they are associated with the contamination of different matrices (soil, water, and air). The present study aimed to carry out a risk assessment to human health of atmospheric pollutants NO2 and SO2 and PM10-bound metal(loid)s in the municipality of Candiota, in addition to evaluating the correlation of meteorological parameters for the dynamics and potential risk of these pollutants. Pollutants were sampled from stations located almost 4 km from coal exploration activities, and the trace elements As, Cd, Se, Pb, and Ni, in addition to NO2 and SO2, were evaluated. Risk assessment was conducted taking into account the risk to adults via the inhalation route. During the sampling period, all pollutants presented values lower than national legislation or internationally accepted values, and Pb was the element that presented the highest values throughout the sampled period. The risk assessment showed no carcinogenic and non-carcinogenic risks, even when considering the sum of the risk of all analyzed pollutants. It can be observed that the highest levels of Pb, As, and Se occurred in the winter season, while the levels of Ni and Cd were higher in the spring, and the meteorological parameters were correlated with the pollutants, even using a temporal lag of 5 days. Although the air pollutants evaluated did not present a risk to human health, continuous monitoring of regions with strong mineral exploration activity must be carried out with a view to maintaining the well-being of exposed populations, mainly because there are people living in areas closer to sources of coal pollution than distance to air quality monitoring stations.

Oxidative damage in the Vesper mouse (Calomys laucha) exposed to a simulated oil spill-a multi-organ study.

Small wild mammals have been used to measure the damage caused by exposure to oil-contaminated soil, including deer mice. However, the study of toxic effects of crude oil using oxidative damage biomarkers in the wild rodent Calomys laucha (Vesper mouse) is absent. This investigation aimed to evaluate the effects of acute exposure to contaminated soil with different concentrations of crude oil (0, 1, 2, 4 and 8% w/w), simulating an accidental spill, using oxidative stress biomarkers in the liver, kidneys, lungs, testes, paw muscle, and lymphocytes of C. laucha. Animals exposed to the contaminated soil showed increases in lipid peroxidation and protein carbonylation at the highest exposure concentrations in most organ homogenates analyzed and also in blood cells, but responses to total antioxidant capacity were tissue-dependent. These results showed that acute exposure to oil-contaminated soil caused oxidative damage in C. laucha and indicate these small mammals may be susceptible to suffer the impacts of such contamination in its occurrence region, threatening the species' survival.

Emissions monitoring and carcinogenic risk assessment of PM10-bounded PAHs in the air from Candiota's coal activity area, Brazil.

The city of Candiota contains a great amount of coal resources. Coal activities, including coal combustion, are major releasers of polycyclic aromatic hydrocarbons (PAHs). The PAHs are considered priority air pollutants regarding their large carcinogenic potential. So, the carcinogenic risk assessment of populations living near areas with PAH sources is mandatory. This study aimed to evaluate the carcinogenic health risk of the PAH inhalation exposure of individuals living in Candiota City. A total of 158 individuals were enrolled in the study. Monitoring of PAH and meteorological parameters were carried out, and the health risk assessment was determined through the benzo(a)pyrene equivalent toxic equivalent quotient (BaP-TEQ) and the incremental lifetime cancer risk (ILCR) estimation. The coal activity area of Candiota demonstrated an annual PAH concentration of 27.7 ng/m3, PM10 concentration of 26.3 µg/m3, SO2 concentration of 9.5 µg/m3, a BaP-TEQ value of 0.3 ng/m3, and a daily inhalation of 62.4 ng/day. The comparison among seasons showed no difference in PAH concentration and BaP-TEQ. It was observed ILCR values of 2.8 × 10-6 and 2.6 × 10-6 for estimation based on reference and real values, respectively, and these levels were above the reference limit of 10-6, indicating cancer risk. Therefore, an epidemiological survey of cancer cases in the region and its relationship with environmental exposure and air pollutants levels must be required.

Gestational and Neonatal Outcomes in Cities in the Largest Coal Mining Region in Brazil.

Brazil has one of the largest mineral coal reserves in the world. More than 40% of this ore is in the Candiota Mine, in the extreme south of Brazil, which was previously identified as a hotspot of environmental pollution. In addition, an important part of Brazil's population suffers from socioeconomic vulnerability. Since there is no information on unfavorable gestational and neonatal outcomes associated with these problems, we conducted a cross-sectional study with 1950 mother-child binomials, aiming to evaluate the association between these outcomes and air pollution as well as socioeconomic, demographic and health variables in seven cities in the region. Of the total births, 11.6% were preterm and 9.5% of neonates had low birth weight (<2500 g). These conditions were also associated with skin color, previous abortions, birth type and prenatal care, as well as exposure to higher levels of coarse particulate matter (PM10) during the first trimester of pregnancy. Regarding air pollutants, although the daily limits for PM10 were exceeded on less than 5% of days, the annual average overtook the values proposed by WHO. Thus, we concluded that prematurity and low birth weight in this region are related to air pollution, and to socioeconomic variables and health care.

Urinary Pb levels in schoolchildren from the largest coal mining area in Brazil and its associated factors: a cross-sectional study.

Candiota region has the largest coal reserve in Brazil, and previous studies have shown moderate-high levels of metals in the environment, including Pb. On the other hand, there are no studies investigating the factors associated with high levels of urinary Pb in children in the region. To investigate this issue, a cross-sectional study was conducted with 92 schoolchildren from 7 cities comprising this coal-mining region. Socioeconomic and demographic information and parental life habits and children's health information were collected using a semi-structured questionnaire. Diurnal urine samples were collected to quantify Pb levels (µg/g creatinine). Bi- and multivariate Poisson regression with a robust estimator was used to assess factors associated with high levels of Pb. Urinary Pb levels in children in the region vary from not detected to 21.6 µg/g of creatinine. The spatial distribution of urinary Pb levels in children indicated an influence of proximity to mining areas, and this factor was confirmed by Poisson regression analysis (bivariate). Other factors associated with high levels of urinary Pb were non-white mothers, paternal occupational exposure, and low BMI. The findings of this study reveal that the Candiota region is a hotspot for high levels of urinary Pb in children (geometric mean: 3.82 µg/g creatinine) and that, in addition to the proximity to mining areas, factors socioeconomic and health conditions may be associated with these high levels.

Curcumin and Quercetin-Loaded Lipid Nanocarriers: Development of Omega-3 Mucoadhesive Nanoemulsions for Intranasal Administration.

Curcumin (CUR) and quercetin (QU) are potential compounds for treatment of brain diseases such as neurodegenerative diseases (ND) because of their anti-inflammatory and antioxidant properties. However, low water solubility and poor bioavailability hinder their clinical use. In this context, nanotechnology arises as a strategy to overcome biopharmaceutical issues. In this work, we develop, characterize, compare, and optimize three different omega-3 (ω-3) fatty acids nanoemulsions (NEs) loaded with CUR and QU (negative, cationic, gelling) prepared by two different methods for administration by intranasal route (IN). The results showed that formulations prepared with the two proposed methods exhibited good stability and were able to incorporate a similar amount of CUR and QU. On the other side, differences in size, zeta potential, in vitro release kinetics, and permeation/retention test were observed. Considering the two preparation methods tested, high-pressure homogenization (HPH) shows advantages, and the CQ NE- obtained demonstrated potential for sustained release. Toxicity studies demonstrated that the formulations were not toxic for Caenorhabditis elegans. The developed ω-3 fatty acid NEs have shown a range of interesting properties for the treatment of brain diseases, since they have the potential to increase the nose-to-brain permeation of CUR and QU, enabling enhanced treatments efficiency.

Toxicity evaluation of traditional and organic yerba mate (Ilex paraguariensis A. St.-Hil.) extracts.

Yerba mate (Ilex paraguariensis A. St.-Hil.) is an important source of biologically active compounds with pharmacological potential. The aim of this study was to examine the toxicity of different extracts obtained from either traditional or organic cultivated yerba mate in vitro and in vivo. Aqueous, ethanolic and methanolic extracts were obtained from commercial samples of yerba mate and total phenolic content was determined employing Folin-Ciocalteau reagent. The aqueous extracts presented higher content of total phenols, compared to ethanolic and methanolic extracts, and also demonstrated lower cytotoxicity, which is the basis for testing were carried out only using aqueous extracts. The main phenolic acids found in traditional aqueous (TA) extract were chlorogenic, gallic and protocatechuic acids. Gallic and hydroxybenzoic acids were detected in aqueous cultivated organic (OA) extract. Pretreatment with OA extract (100 µg/ml, 1 hr) was cytoprotective against rotenone-induced toxicity (1 µM). For in vivo toxicity assay, zebrafish embryos were exposed to OA or TA extracts (10-160 µg/ml) at 4 hr post fertilization. TA extract decreased embryos survival in a concentration-dependent manner, reduced the hatching rate at 40 µg/ml, increased edema frequency at 80 µg/ml and altered body curvature at 120 µg/ml. Further, TA extract produced locomotor disorders at concentrations equal to or greater than 10 µg/ml. In contrast, OA extract exhibited no apparent toxic effect on organogenesis and behavior up to 100 µg/ml. In summary, the OA cultivated extract showed the lowest cytotoxicity in vitro, enhanced reduction in rotenone-induced toxicity, and produced less toxicity in zebrafish embryos compared to the TA extract.

Neuroprotective Effects of Resveratrol in In vivo and In vitro Experimental Models of Parkinson's Disease: a Systematic Review.

Parkinson's disease (PD) is currently the second most common neurodegenerative disease, being characterized by motor and non-motor symptoms. The therapeutic options available for its treatment are limited, do not slow the progression of the disease, and have serious side effects. For this reason, many studies have sought to find compounds with neuroprotective properties that bring additional benefits to current therapy. In this context, resveratrol is a phenolic compound, found in many plant species, capable of crossing the blood-brain barrier and having multiple biological properties. Experimental studies in vitro and in vivo have shown that it can prevent or slow the progression of a variety of diseases, including PD. In this systematic review, we summarize the effects of resveratrol in experimental in vivo and in vitro models of PD and discuss the molecular mechanisms involved in its action. The bibliographic search was performed in the databases of PubMed, Web of Science, SciELO, and Google Scholar, and based on the inclusion criteria, 41 articles were selected and discussed. Most of the included studies have demonstrated neuroprotective effects of resveratrol. In general, resveratrol prevented behavioral and/or neurological disorders, improved antioxidant defenses, reduced neuroinflammatory processes, and inhibited apoptosis. In summary, this systematic review offers important scientific evidence of neuroprotective effects of resveratrol in PD and also provide valuable information about its mechanism of action that can support future clinical studies.

Phenolic compounds and antioxidant capacity of Pediastrum boryanum (Chlorococcales) biomass.

Bioactive compounds, synthesized by photosynthetic microorganisms, have drawn the attention of the pharmaceutical field. This study aimed at evaluating synthesis and in vitro antioxidant capacity of phenolic compounds produced by a microalgae species P. boryanum, which was grown in six different culture media (standard BG11, modified BG11/MBG11, standard WC, modified WC, WC*2 and basal). The highest concentrations of biomass (1.75 ± 0.01 g.L-1) and phenolic content (3.18 ± 0.00 mg.g-1) were obtained when P. boryanum was grown in MBG11 and phenolic acids were identified: gallic, protocatechuic, chlorogenic, hydroxybenzoic and vanillic ones. All extracts exhibited scavenger activity in the ABTS assay and inhibited peroxidase. However, phenolic compounds from P. boryanum grown in BG11 and MBG11 had the most potent scavenger activity in the DPPH assay. In sum, P. boryanum can be a new source of free phenolic compounds with potential antioxidant activity when grown in MBG11, since it yields high amounts of biomass and phenolic compounds.

Health impact assessment of air pollution in an area of the largest coal mine in Brazil.

Coal exploration and burning activities are among the activities with the greatest potential to cause atmospheric pollution due to the combustion process of this mineral and the consequent release of particles that, in significant quantities, can pose a potential health risk, mainly respiratory and cardiovascular diseases. The Candiota region, in the extreme south of Brazil, concentrates 40% of the national reserves of mineral coal, and its burning is capable of releasing air pollutants, including particulate matter (PM). Some environmental and epidemiological studies have been carried out in the region, but so far, there is no investigation to estimate the impact of PM on health outcomes. The current study aimed to estimate the mortality attributed to the PM, as well as the benefits in health indicators associated with the reduction of air pollution to the limits set forth in local legislation and the WHO. Daily data on PM levels collected from an air quality monitoring station over a year were used, as well as population data and health indicators from 7 cities influenced by mining activities, such as total mortality and cardiovascular diseases and hospitalizations for cardiac and respiratory problems. In a scenario where PM levels are within legal limits, a percentage greater than 11% of cardiovascular deaths was attributed to pollution by PM2.5, and the reduction in PM10 and PM2.5 levels may be responsible for the increase in the expectation of life in up to 17 months and monetary gains of more than $ 24 million, due to the reduction in hospitalizations and mortality. Studies of this nature should be important tools made available to decision-makers, with a view to improving environmental laws and a consequent improvement in the quality of life and health indicators of the population.

Unexpected reduction in ozone levels in a mid-size city during COVID-19 lockdown.

The current study evaluated ozone levels through passive samplers installed in 4 different points in a medium-sized city (Rio Grande, Brazil) with naturally low NO2 levels during a week of COVID-19 lockdown. Additionally, we evaluated the consequences of this response with regard to human health risk assessment and reduction of hospital admissions and ozone-related deaths. The reduction in ozone levels, one month after the implementation of containment measures, varied between 26 and 64% (average of 44%), in the different studied sites. The reduction of human mobility during the pandemic reduced the levels of ozone in Rio Grande city and consequently will bring benefits to health services in the municipality. This unexpected reduction in O3 levels must be related to the low 'natural' levels of NO2 in the city, which make the contribution of other precursors important for the fluctuation of O3 levels.

Development of Lipid Nanocarriers for Tuberculosis Treatment: Evaluation of Suitable Excipients and Nanocarriers.

BACKGROUND: Lipid nanocarriers have been widely tested as drug delivery systems to treat diseases due to their bioavailability, controlled release, and low toxicity. For the pulmonary route, the Food and Drug Administration favors the use of substances generally recognized as safe, as well as biodegradable and biocompatible to minimize the possibility of toxicity. Tuberculosis (TB) remains a public health threat worldwide, mainly due to the long treatment duration and adverse effects. Therefore, new drug delivery systems for treating TB are needed. OBJECTIVE: Physicochemical characterization of different lipid-based nanocarriers was used to optimize carrier properties. Optimized systems were incubated with Mycobacterium tuberculosis to assess whether lipid-based systems act as the energy source for the bacteria, which could be counterproductive to therapy. METHODS: Several excipients and surfactants were evaluated to prepare different types of nanocarriers using high-pressure homogenization. RESULTS: A mixture of trimyristin with castor oil was chosen as the lipid matrix after differential scanning calorimetry analysis. A mixture of egg lecithin and PEG-660 stearate was selected as an optimal surfactant system, as this mixture formed the most stable formulations. Three types of lipid nanocarriers, solid lipid nanoparticles, nanostructured lipid carriers (NLC), and nanoemulsions, were prepared, with the NLC systems showing the most suitable properties for further evaluation. It may provide the advantages of increasing the entrapment efficiency, drug release, and the ability to be lyophilized, producing powder for pulmonary administration as an alternative to entrap poor water-soluble molecules. CONCLUSION: Furthermore, the NLC system can be considered for use as a platform for the treatment of TB through the pulmonary route.

Maternal, neonatal and socio-economic factors associated with intellectual development among children from a coal mining region in Brazil.

Coal is the most aggressive energy sources in the environment. Several adverse outcomes on children's health exposure to coal pollutants have been reported. Pollutants from coal power plants adversely affect the intellectual development and capacity. The present study aimed to evaluate the intellectual development and associated factors among children living a city under the direct influence (DI) and six neighboring municipalities under the indirect influence (II) of coal mining activity in the largest coal reserve of Brazil. A structured questionnaire was completed by the child's guardian, and Raven's Progressive Color Matrices were administered to each child to assess intellectual development. A total of 778 children participated. In general, no significant difference was observed between the two cities. The DI city had better socioeconomic conditions than the II municipalities according to family income (< 0.001). The prevalence of children who were intellectually below average or with intellectual disabilities was 22.9%, and there was no significant difference (p > 0.05) between municipalities. In both unadjusted and adjusted analyses, intellectual development was associated with maternal age, marital situation and maternal education level, birth weight, breast feeding, frequent children's daycare, paternal participation in children's care and child growth. Living in the DI area was not associated with intellectual disability. The results suggest that socioeconomic conditions and maternal and neonatal outcomes are more important than environmental factors for intellectual development of children living in a coal mining area.

Blood markers among residents from a coal mining area.

Coal extraction and processing generate environmental contamination, which has several negative impacts on human health. Hematological and biochemical parameters are effective biomarkers of the exposure of a population to air pollutants. Thus, this study aimed to evaluate hematological and biochemical parameters in adult residents in a coal mining region in the largest national reserve in Brazil, as well as to investigate their relations with air quality. The study included three cities in the south of Brazil, which are located near an important power plant and coal mine. The air quality was analyzed by PM10, NOx, and SO2 at five air quality monitoring stations, socioeconomic and demographic characteristics were evaluated with a questionnaire, and biochemical parameters were assessed in blood samples. The mean PM10 in the study area was 19.18 µg/m3. The air quality varied among the five monitoring stations, and the Candiota station exceeded the reference limit by 63.3%. In general, participants had lived more than 10 years in the municipality and had hepatic and renal parameters within the reference values. A higher prevalence of alterations was found in hematological parameters (43.1%) and liver function (30%). Among the three cities, the population of Pedras Altas seems to have a greater impairment of the blood parameters evaluated. The only parameter that was correlated with PM10 was the hematocrit level (r = 0.33; P < 0.001).

Multimarker approach to assess the exposure of the wild rodent Calomys laucha to a simulated crude oil spill.

A mysterious oil spill occurred in the ocean near Brazil in 2019, which affected coastal areas in northeastern Brazil. When oil pollution occurs in coastal zones, organisms such as small mammals can suffer deleterious effects to their health. This study aimed to evaluate the effects of exposure to contaminated sandy soil with different crude oil concentrations in males of the species Calomys laucha. The exposure to crude oil resulted in multiple health issues for the subjects in the very first days of exposure. Furthermore, the exposure resulted in mutagenic damage to bone marrow blood cells and behavioral and morphological alterations, which were almost always in a dose-dependent form. The present study demonstrates the sensibility of the biomarkers used and highlights that small wild mammals such as C. laucha are useful for predicting environmental damage caused by the exposure to crude oil.