Toxicological Effects of Fine Particulate Matter (PM2.5): Health Risks and Associated Systemic Injuries-Systematic Review.

Previous studies focused on investigating particulate matter with aerodynamic diameter ≤ 2.5 µm (PM2.5) have shown the risk of disease development, and association with increased morbidity and mortality rates. The current review investigate epidemiological and experimental findings from 2016 to 2021, which enabled the systemic overview of PM2.5's toxic impacts on human health. The Web of Science database search used descriptive terms to investigate the interaction among PM2.5 exposure, systemic effects, and COVID-19 disease. Analyzed studies have indicated that cardiovascular and respiratory systems have been extensively investigated and indicated as the main air pollution targets. Nevertheless, PM2.5 reaches other organic systems and harms the renal, neurological, gastrointestinal, and reproductive systems. Pathologies onset and/or get worse due to toxicological effects associated with the exposure to this particle type, since it can trigger several reactions, such as inflammatory responses, oxidative stress generation and genotoxicity. These cellular dysfunctions lead to organ malfunctions, as shown in the current review. In addition, the correlation between COVID-19/Sars-CoV-2 and PM2.5 exposure was also assessed to help better understand the role of atmospheric pollution in the pathophysiology of this disease. Despite the significant number of studies about PM2.5's effects on organic functions, available in the literature, there are still gaps in knowledge about how this particulate matter can hinder human health. The current review aimed to approach the main findings about the effect of PM2.5 exposure on different systems, and demonstrate the likely interaction of COVID-19/Sars-CoV-2 and PM2.5.

Consumption of mate Ilex paraguariensis: a folk beverage with antioxidant power against myocardial ischemic injury

The effects of the aqueous extract of Ilex paraguariensis (Ip)and the flavonoid quercetin were tested during the induction of in vivomyocardial ischemia/ reperfusion in Rattus norvegicus. The antioxidant power of the extract and quercetin were chemically determined. The experimental groups were: control, ischemia/reperfusion induction, Iporal treatment, Iporal treatment and ischemia /reperfusion, quercetin oral treatment, and quercetin oral treatment and ischemia/reperfusion. Rats were anesthetized with sodium thiopental and xylazine via intraperitoneal injection and subsequently underwent 15 minutes of ischemia followed by 15 minutes of reperfusion. Ischemia was promoted by tying the left anterior descending coronary artery. Areas of risk and infarction were stained by intravenous Evans blue and triphenyl tetrazolium chloride. Reactive oxygen species (ROS), antioxidant capacity against peroxylradicals, and lipid peroxidation of the myocardium were quantified. A significant reduction in areas of risk and infarction was detected in the ischemic myocardium treated with Ipand quercetin; ROS generation and lipid peroxidation were significantly reduced, and the antioxidant capacity was elevated. Oral administration of Ippromoted antioxidant benefits in the myocardium during ischemia and reperfusion, which reduced infarction. We suggest that Mate (a hot drink made from steeped dried leaves of Ip) consumption is a potential cardioprotective habit of indigenous people from southern South American countries, which must be better understood scientifically and ethnographically.

Assessment of the effects of seasonality on the ecotoxicity induced by the particulate matter using the animal model Caenorhabditis elegans.

The present work aimed to establish potential changes in the ecotoxicological effects on C. elegans induced by the exposure of coarse (PM10) and fine (PM2.5) particulate matter collected during dry and rainy periods. We also analyzed the probable influence on the change of a city's activities as the mega-events result in air quality. The element levels evaluation was performed on PM, on the solutions of exposure, and C. elegans after exposure. Biochemical essays were performed to evaluate damage to C. elegans. The results showed that infrastructure works increased the levels of pollutants, generating increases in the concentrations of PM2.5 and PM10. The biochemical results suggested effects mediated by different mechanisms, where PM2.5 induced an increase in antioxidant capacity with activation of the defense system and lipoperoxidation. Results suggest that PM10 reduces the antioxidant capacity and activates the glutathione S-transferase activity enzymatic action, but also induces lipoperoxidation in all groups of animals exposed to samples collected during the dry period of 2016. Individuals exposed to PM2.5 in 2017 wet and dry periods and PM10 in 2016 and 2017 dry periods shown a decrease in size compared to controls, while for fertility data, there was a decrease only in individuals exposed to PM2.5 in the periods that the highest levels of PM concentration. We conclude that despite the positive issues linked to the hosting of mega-events, their infrastructure requirements can compromise air quality and bring damage related to lipoperoxidation and physiological changes in the life cycle of biological systems, such as what happened to C. elegans exposed to tested extracts. Also, rainy events reduced the presence of these pollutants, washing the atmosphere.

Assessment of air quality changes during COVID-19 partial lockdown in a Brazilian metropolis: from lockdown to economic opening of Rio de Janeiro, Brazil.

Abstract: During the COVID-19 pandemic, restrictive measures are taken by several cities around the world, as well as Rio de Janeiro, reducing routine activities in large urban centers and primary pollutant emissions. This study aims to assess air quality during this partial lockdown through O3, CO, and PM10 concentrations and meteorological data collected in five air quality monitoring stations spread over the whole city, considering the substantial changes in city routine. The period evaluated starts in March 2020, when the partial lockdown was decreed, and ends in September 2020, when economic opening ended. Compared with 2019 data, CO concentration reduced significantly, as expected since the main source of these pollutants is vehicular traffic. O3 concentration increased, most probably as a consequence of the reduction in primary pollutants. On the other hand, PM10 concentration did not vary significantly. From June to September, pollutant concentrations increased responding to the economic opening. Thereby, the partial lockdown contributed to improving air quality in Rio de Janeiro City, which means that changes in work format may be an alternative to reduce atmospheric pollution in big cities, since home office contributes to mobility reductions, and consequently to vehicular emissions. Highlights: • Lockdown contributed to CO reduction and O3 increase.• Differences on rain profile explain low variation on PM10 concentrations.• Lockdown has been like a very long weekend concerning atmospheric pollution.• Home office and distance learning improve air quality. Supplementary Information: The online version contains supplementary material available at 10.1007/s11869-021-01127-2.

Cardioprotective effect of eicosapentaenoic acid during ischemia and reperfusion / Efeito cardioprotetor do ácido eicosapentaenóico durante a isquemia e reperfusão

Objective: In this work, rats isolated hearts were infused EPA before the ischemia period and during reperfusion for available get well in parameter relatives to redox reactions. Methods: The effect of EPA was tested on isolated hearts induced to ischemia and reperfusion, treatment occurred at different times (ischemia or reperfusion). Antioxidant capacity against peroxyl radicals, glutathione cysteine ligase activity, glutathione concentration, lactate dehydrogenase, and creatine kinase concentration was analyzed. Results: Hearts treated with eicosapentaenoic acid had the minor generation of species reactive oxygen and lipid damage after reperfusion. The GSH concentration was higher when the hearts were treated with eicosapentaenoic acid in the period of reperfusion. Conclusion: In conclusion, this study demonstrates that the dose of EPA (20µM) used before ischemia can act as a cardioprotective antioxidant molecule, prevented damage heart from ischemic and reperfusion injury

Objetivo: Neste trabalho, corações isolados de ratos foram infundidos com EPA antes do período de isquemia e durante a reperfusão para obtenção de melhora em parâmetros relativos às reações redox. Métodos: O efeito do EPA foi testado em corações isolados induzidos a isquemia e reperfusão, o tratamento ocorreu em diferentes momentos (isquemia ou reperfusão). A capacidade antioxidante contra os radicais peroxil, atividade da glutationa cisteína ligase, concentração de glutationa, lactato desidrogenase e concentração de creatina quinase foi analisada. Resultados: Corações tratados com ácido eicosapentaenóico tiveram a menor geração de espécies reativas de oxigênio e danos lipídicos após a reperfusão. A concentração de GSH foi maior quando os corações foram tratados com ácido eicosapentaenóico no período de reperfusão. Conclusão: Em conclusão, este estudo demonstra que a dose de EPA (20µM) utilizada antes da isquemia pode atuar como uma molécula antioxidante cardioprotetora, prevenindo danos ao coração por isquemia e lesão de reperfusão.

Long-chain fatty dihydropyridines: Docking calcium channel studies and antihypertensive activity.

AIMS: From the synthesis of 43 lipophilic dihydropyridines, the aim of this study was to verify whether the new dihydropyridines have calcium channel affinity using coupling studies and to determine antihypertensive and antioxidant properties, as well as toxicology and toxicity nifedipine and three new compounds, were chosen from the previous results. MATERIALS AND METHODS: The animals were treated for 56 days, 28 days with N (ω) -nitro-L-arginine methyl ester to induce hypertension, and then treated for another 28 days with the new di- hydropyridine and the standard drug nifedipine. Throughout the treatment the animals had their blood pressure measured and their heart rate checked by pletysmography. After treatment the animals were euthanised, blood samples were collected for creatine kinase and urea analysis, and the brain, heart and liver were collected for oxidative status analysis (quantification of reactive oxygen species, total antioxidant capacity, and lipid peroxidation). KEY FINDINGS: Compounds 2c, and 9a, and nifedipine significantly reduced blood pressure to control group levels. The tachycardia caused by the induction of hypertension was reversed by 2c and 9a compounds. Regarding oxidative stress analyzes, the compounds that had the best performances were also 2c and 9a. Overall the results demonstrate that two of the three new dihydropyridines tested demonstrated performance equal to or superior to the standard drug nifedipine. SIGNIFICANCE: In this study, for the first time, docking was applied to analyse 43 fatty dihydropyridines regarding their calcium channel binding. Afterwards, three fatty dihydropyridines were chosen and their antihypertensive and antioxidant properties.

Effect of pristine fullerene on acquisition, consolidation and retrieval memory in wistar rats.

The present study evaluated the effect of fullerene (C60) under in vitro conditions, in hippocampus homogenates from rats and on the induction of behavioral disabilities. Exposure to in vitro C60 led to an increase in the concentration of reactive oxygen species (ROS) and lipid peroxidation (LPO) of hippocampus treated with of fullerene and suspension. These results indicate that the oxidative stress caused by the exposure to C60 was in part related to an absence of an antioxidant response. In this sense, one-trial inhibitory avoidance task were performed and results showed that fullerene at 0.2 and 0.45 µm impaired the acquisition and consolidation of short and long-term memory. Further, enzymatic analysis in rat hippocampus were not significantly different, however, there was an increase in the content of LPO and ROS produced by fullerene. Overall, the results indicates that fullerene possess neurotoxic properties that impairs behavior and promotes oxidative stress.

Evaluation of the antioxidant activities of fatty polyhydroquinolines synthesized by Hantzsch multicomponent reactions.

Polyhydroquinolines (PHQs) are the unsymmetrical Hantzsch derivatives of 1,4-dihydropyridines with several biological applications. In this work, new fatty 2- and 3-substituted PHQ derivatives from different fatty acids and fatty alcohol feedstocks were synthesized at good yields via a four-component reaction (4CR). The antioxidant activities of fatty PHQs were investigated using three different antioxidant methods. The experiments showed that the compounds derived from 2-nitrobenzaldehyde and fatty palmitic (C16:0) and oleic (C18:1) chains showed better antioxidant activity. This revealed that combining the ortho NO2 group in the aromatic ring with the insertion of fatty chains in the PHQ core contributed to the antioxidant activity. However, among all the fatty PHQs tested, the fatty 2-substituted compound derived from oleyl alcohol and 2-nitrobenzaldehyde showed the highest antioxidant activity (EC50, 2.11-4.69 µM), which was similar to those of the antioxidant standards butylated hydroxytoluene (EC50, 1.98-6.47 µM) and vitamin E (EC50, 1.19-5.88 µM). In addition, this lipophilic compound showed higher antioxidant activity than the antihypertensive drug nifedipine (EC50, 49.25-126.86 µM). These results indicate that the new fatty PHQs may find novel applications as antioxidant additives.

New fatty dihydropyridines present cardioprotective potential in H9c2 cardioblasts submitted to simulated ischemia and reperfusion.

Nifedipine is a calcium channel blocker dihydropyridine that has been used in the treatment of hypertension. The production of reactive species and calcium overload are the main contributors to myocardial ischemia-reperfusion (I / R) injury. We investigated the ability of novel dihydropyridines (DHPs) to improve the effect of protecting against the injury induced by ischemia and reperfusion in cardioblasts when compared to nifedipine. Forty three DHPs were created varying the fatty chains derived from palmitic acid, stearic acid and oleic acids and aromatic moiety in addition to the addition of chemical elements such as chlorine, nitrogen dioxide, furfural, hydroxyl and methoxy. Cytotoxicity and inhibition of linoleic oxidation were evaluated for all new DHPs and also for nifedipine. The alpha-tocopherol and butylated hydroxytoluene (BHT) were used as antioxidants controls. The compounds with the best antioxidant potential were used in the ischemia and reperfusion (I / R) induction test in cardioblasts (H9c2). Cardioblasts were treated 24 h after assembly of plates and submitted to the ischemia simulation (30 min), after which, normoxia and cellular nutrition conditions were reestablished, simulating reperfusion (additional 30 min). Right after, cell viability, apoptosis, necrosis, and the generation of reactive oxygen species (ROS) were evaluated. Cell viability during I / R was not altered in cells treated with nifedipine, BHT and the new DHP composed of palmitic acid with hydroxyl group in the aromatic substituent. The other new DHPs increased cell viability during I / R simulation and reduced levels of reactive species compared to the I / R group, demonstrating the antioxidant capacity of the new DHPs. Therefore, DHPS with palmitic and oleic acids in the C3 and C5 position with NO2 or Cl in aromatic moiety, presented the highest antioxidant potential (linoleic oxidant test). The new DHPs increased cell viability during I / R simulation and reduced levels of reactive species compared to the ischemia and reperfusion group, demonstrating the antioxidant capacity of the new DHPs. Taken together, these results indicate that those new DHPs have a greater cardioprotective antioxidant capacity to face the damages of ischemia and reperfusion.

Synthesis and antioxidant activity of new lipophilic dihydropyridines.

Dihydropyridines (DHPs) obtained from Hantzsch multicomponent reactions are an important pharmaceutical class of compounds marketed as antihypertensive (e.g., nifedipine, nitrendipine, and amlodipine) drugs. This study synthesized new symmetrical and unsymmetrical long-chain fatty DHPs using multicomponent reactions under metal-free conditions with sulfamic acid as a catalyst. The DHPs were tested for antioxidant activity using three different methods. The insertion of a long chain into the DHP core contributed to antioxidant potential, and compounds derived from nitro aldehydes have better antioxidant potential than the antihypertensive drug nifedipine. In addition, fatty analogs to nifedipine derived from palmitic and oleic chains showed similar antioxidant activity to the common standards butylated hydroxytoluene and vitamin E. These results showed that our new synthesized products may find novel applications as antioxidant additives or for tools for use in drug discovery.

Protective role of the novel hybrid 3,5-dipalmitoyl-nifedipine in a cardiomyoblast culture subjected to simulated ischemia/reperfusion.

This work investigated the acute effects of the calcium channel blocker nifedipine and its new fatty hybrid derived from palmitic acid, 3,5-dipalmitoyl-nifedipine, compared to endocannabinoid anandamide during the process of inducing ischemia and reperfusion in cardiomyoblast H9c2 heart cells. The cardiomyoblasts were treated in 24 or 96-well plates (according to the test being performed) and maintaining the treatment until the end of hypoxia induction. The molecules were tested at concentrations of 10 and 100µM, cells were treated 24h after assembling the experimental plates and immediately before the I/R. Cell viability, apoptosis and necrosis, and generation of reactive oxygen species were evaluated. Nifedipine and 3,5-dipalmitoyl-nifedipine were used to assess radical scavenging potential and metal chelation. All tested molecules managed to reduce the levels of reactive oxygen species compared to the starvation+vehicle group. In in vitro assays, 3,5-dipalmitoyl-nifedipine showed more antioxidant activity than nifedipine. These results indicate the ability of this molecule to act as a powerful ROS scavenger. Cell viability was highest when cells were induced to I/R by both concentrations of anandamide and the higher concentration of DPN. These treatments also reduced cell death. Therefore, it was demonstrated that the process of hybridization of nifedipine with two palmitic acid chains assigns a greater cardioprotective effect to this molecule, thereby reducing the damage caused by hypoxia and reoxygenation in cardiomyoblast cultures.