First in class pyrrolo[2,3-d]pyrimidine derivatives fused to fluorobenzylpiperidines as dual ligands of acetylcholinesterase and histamine H receptor.

Alzheimer's disease (AD) is a multifactorial neurodegenerative disease with manifold underlying pathophysiological mechanisms. Therefore, multitarget-directed ligands potentially offer beneficial therapeutic effects compared with classical therapies. Dual targeting of the histamine H receptor (HR) and acetylcholinesterase (AChE) is a valid strategy for the treatment of AD.

Photoaged polystyrene nanoplastics exposure results in reproductive toxicity due to oxidative damage in Caenorhabditis elegans.

The increase of plastic production together with the incipient reuse/recycling system has resulted in massive discards into the environment. This has facilitated the formation of micro- and nanoplastics (MNPs) which poses major risk for environmental health. Although some studies have investigated the effects of pristine MNPs on reproductive health, the effects of weathered MNPs have been poorly investigated.

Beneficial antioxidant effects of Coenzyme Q10 on reproduction.

This chapter focuses on preclinical and clinical studies conducted in recent years that contribute to increasing knowledge on the role of Coenzyme Q10 in female reproductive health. General aspects of CoQ10, such as its role as an antioxidant and in mitochondrial bioenergetics are considered. The age-dependent decline in human female reproductive potential is associated with cellular mitochondrial dysfunction and oxidative stress, and in some cases accompanied by a decrease in CoQ10 levels.

Evidence on Neurotoxicity after Intrauterine and Childhood Exposure to Organomercurials.

Although the molecular mechanisms underlying methylmercury toxicity are not entirely understood, the observed neurotoxicity in early-life is attributed to the covalent binding of methylmercury to sulfhydryl (thiol) groups of proteins and other molecules being able to affect protein post-translational modifications from numerous molecular pathways, such as glutamate signaling, heat-shock chaperones and the antioxidant glutaredoxin/glutathione system. However, for other organomercurials such as ethylmercury or thimerosal, there is not much information available. Therefore, this review critically discusses current knowledge about organomercurials neurotoxicity-both methylmercury and ethylmercury-following intrauterine and childhood exposure, as well as the prospects and future needs for research in this area.

Effects of native forest and human-modified land covers on the accumulation of toxic metals and metalloids in the tropical bee Tetragonisca angustula.

The intensive shift on land cover by anthropogenic activities have led to changes in natural habitats and environmental contamination, which can ultimately impact and threat biodiversity and ecosystem services, such as pollination. The aim of this study was to evaluate the effect of native forest and human-modified land covers on the concentrations of chemical elements accumulated in the neotropical pollinator bee T. angustula.

Global liver proteomic analysis of Wistar rats chronically exposed to low-levels of bisphenol A and S.

Exposure to bisphenol A (BPA) and bisphenol S (BPS) has been associated with the development of metabolic disorders, such as obesity, dyslipidemias, and nonalcoholic fatty liver disease. Nonetheless, the associated mechanisms are still not fully understood. BPS is being used with no restrictions to replace BPA, which increases the concern regarding its safety and claims for further investigation on its potential mechanisms of toxicity.

Antioxidant CoQ10 Restores Fertility by Rescuing Bisphenol A-Induced Oxidative DNA Damage in the Germline.

Endocrine-disrupting chemicals are ubiquitously present in our environment, but the mechanisms by which they adversely affect human reproductive health and strategies to circumvent their effects remain largely unknown. Here, we show in that supplementation with the antioxidant Coenzyme Q10 (CoQ10) rescues the reprotoxicity induced by the widely used plasticizer and endocrine disruptor bisphenol A (BPA), in part by neutralizing DNA damage resulting from oxidative stress. CoQ10 significantly reduces BPA-induced elevated levels of germ cell apoptosis, phosphorylated checkpoint kinase 1 (CHK-1), double-strand breaks (DSBs), and chromosome defects in diakinesis oocytes.

Long-term exposure to bisphenol A or S promotes glucose intolerance and changes hepatic mitochondrial metabolism in male Wistar rats.

The present study evaluates the effects of low-level long-term exposure to bisphenol A (BPA) and bisphenol S (BPS) on serum biochemical markers, glucose homeostasis, mitochondrial energy metabolism, biogenesis and dynamics, and redox status in livers of Wistar rats. While only the exposure to BPS induces a significant body mass gain after 21 weeks, both compounds alter serum lipid levels and lead to the development of glucose intolerance. Regarding mitochondrial metabolism, both bisphenols augment the electron entry by complex II relative to complex I in the mitochondrial respiratory chain (MRC), and reduce mitochondrial content; BPA reduces OXPHOS capacity and uncouples respiration (relative to maximal capacity of MRC) but promotes a significant increase in fatty acid oxidation.

Gold-Coated Superparamagnetic Iron Oxide Nanoparticles Attenuate Collagen-Induced Arthritis after Magnetic Targeting.

The aim of the study was to evaluate if gold-coated superparamagnetic iron oxide nanoparticles (AuSPION) magnetic-targeted to the arthritic articulation of collagen induced arthritis (CIA) rats are able to ameliorate rheumatoid arthritis without producing significant biological adverse effects in comparison to colloidal Au nanoparticles (AuC) and metotrexate (MTX). Male Wistar rats were divided into control; arthritic; AuSPION (150 μg kg); AuC (150 μg kg) and MTX (2.5 μg kg).

Niacin prevents mitochondrial oxidative stress caused by sub-chronic exposure to methylmercury.

Humans and animals can be exposed to different chemical forms of mercury (Hg) in the environment. For example, methylmercury (MeHg)-contaminated fish is part of the basic diet of the riparian population in the Brazilian Amazon Basin, which leads to high total blood and plasma Hg levels in people living therein. Hg induces toxic effects mainly through oxidative stress.

The impact of occupational exposure to traffic-related air pollution among professional motorcyclists from Porto Alegre, Brazil, and its association with genetic and oxidative damage.

Vehicles play an important role in modern life; however, they also generate hazards. Occupational exposed subjects are in long-term contact with harmful products, which sets these professionals in a susceptible group to air pollutant damage. The aims of this study were to quantify individual exposure to pollutant gases and chemical elements and to evaluate oxidative and genetic damage in professional motorcyclists and office workers.

Evaluation of distribution, redox parameters, and genotoxicity in Wistar rats co-exposed to silver and titanium dioxide nanoparticles.

The increasing production of silver nanoparticles (AgNPs) and titanium dioxide nanoparticles (TiONPs) has resulted in their elevated concentrations in the environment. This study was, therefore, aimed at determining the distribution, redox parameters, and genotoxic effects in male Wistar rats that were treated with either AgNP or TiONP individually, as well as under a co-exposure scenario. Animals were exposed via oral gavage to either sodium citrate buffer (vehicle), 0.

Long-Term Excessive Selenium Supplementation Induces Hypertension in Rats.

Selenium (Se) is an essential trace element involved in several biological pathways, naturally found in rocks, soils, and food. Even though the daily requirement of Se is achieved through a balanced diet, the use of Se supplements has been frequent. Due to the risk of toxic effects of having Se in excess, supplementation is still under debate.

The use of tree barks and human fingernails for monitoring metal levels in urban areas of different population densities of Porto Alegre, Brazil.

The aim of this study was to evaluate the use of tree barks as a bioindicator of atmospheric pollution in areas of contrasting population densities and to associate the levels of elements found in this bioindicator with those obtained in fingernail samples collected from students living in the same study areas. Tree bark samples were collected from urban areas near highways in regions with high (Area A), intermediate (Area B), and low (Area C) population densities of Porto Alegre, Brazil, and evaluated for chemical elements concentration. Since these areas also differed in traffic density, NO was measured by passive sampling.

Gold nanoparticles: A critical review of therapeutic applications and toxicological aspects.

Gold (Au) compounds have been utilized as effective therapeutic agents for the treatment of some inflammatory diseases such as rheumatoid arthritis. However, Au compound use has become limited due to associated high incidence of side effects. Recent development of nanomaterials for therapeutic use with Au-containing drugs is improving the beneficial actions and reducing toxic properties of these agents.

Protective effects of niacin against methylmercury-induced genotoxicity and alterations in antioxidant status in rats.

This study investigates the potential beneficial effects of niacin (NA; vitamin B3) supplementation in rats chronically exposed to methylmercury (MeHg). Animals were randomly assigned to one of 4 groups (n = 6): Group I, control, received distilled water by gavage; Group II, received MeHg (100 µg/kg/d) by gavage; Group III, received NA (50 mg/kg/d) in drinking water; Group IV, received MeHg (100 µg/kg/d) by gavage + NA (50 mg/kg/d) in drinking water. Biochemical parameters levels of glucose, triglycerides, total cholesterol and fractions, and enzyme activities aspartate transaminase (AST) and alanine transaminase (ALT) were determined.

Monitoring an outdoor smoking area by means of PM measurement and vegetal biomonitoring.

The extension of pollutant accumulation in plant leaves associated with its genotoxicity is a common approach to predict the quality of outdoor environments. However, this approach has not been used to evaluate the environmental quality of outdoor smoking areas. This study aims to evaluate the effects of environmental tobacco smoke (ETS) by assessing particulate matter 2.

A systematic study of the disposition and metabolism of mercury species in mice after exposure to low levels of thimerosal (ethylmercury).

Thimerosal (TM) is an ethylmercury (etHg)-containing preservative used in some vaccines despite very limited knowledge on the kinetics and direct interaction/effects in mammals׳ tissues after exposure. Thus, this study aimed to evaluate the kinetics of Hg species in mice in a time course analysis after intramuscular injection of TM, by estimating Hg half-lives in blood and tissues. Mice were exposed to one single intramuscular dose of 20 µg of Hg as TM.

Trace elements concentration in nails and association with airway inflammation in adolescents.

Asthma is a multifactorial disease and its severity varies with the inflammatory status of the patient. It has been hypothesized that deficiency of trace elements has an important role in the etiology of asthma. The aim of the study was to evaluate the concentration of trace elements in nails of adolescents with different degrees of airway inflammation.

Thimerosal induces apoptotic and fibrotic changes to kidney epithelial cells in vitro.

Thimerosal is an ethyl mercury-containing compound used mainly in vaccines as a bactericide. Although the kidney is a key target for mercury toxicity, thimerosal nephrotoxicity has not received the same attention as other mercury species. The aim of this study was to determine the potential cytotoxic mechanisms of thimerosal on human kidney cells.

Phytoremediation potential of Maná-Cubiu (Solanum sessiliflorum Dunal) for the deleterious effects of methylmercury on the reproductive system of rats.

Methylmercury, organic form of mercury, can increase the number of abnormal sperm and decrease sperm concentration and testosterone levels possibly due to the damage caused by reactive species to germ and Leydig cells. Maná-cubiu (Solanum sessiliflorum Dunal) is a native fruit from Amazon rich in iron, zinc, niacin, pectin, and citric acid, used in foods, beverages, and medicinal purposes, since it has been useful for treatment of various diseases caused by oxidative stress or nutritional deficiency. Therefore, this study evaluated the phytoremediation potential of this fruit on damages caused by exposure to MeHg on sperm quantity and quality and the histological aspect of the testis and epididymis.

Inorganic and methylmercury levels in plasma are differentially associated with age, gender, and oxidative stress markers in a population exposed to mercury through fish consumption.

This study aimed to determine the concentrations of plasma methylmercury (Me-Hg) and inorganic mercury (I-Hg) in a population exposed to Me-Hg. In addition, associations between each form of mercury (Hg) and gender, age, plasma selenium (Se), and oxidative stress markers were also investigated. The mean plasma I-Hg level was 5.