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-1); AuC (150 µg kg-1) and MTX (2.5 µg kg-1). Treatments were administered thrice every other day by the intraperitoneal route 15 min after all groups had a neodymium magnet coupled to the right ankle joint (kept for 1 h). Paw edema and body weight were measured weekly. Joint sections were evaluated by Haematoxylin & Eosin and immunohistochemistry (TNF-α, IL-1ß). Biomarkers of oxidative stress were used to evaluate toxicity. Among the evaluated treatments, AuSPION led to significant clinical improvements (decreased edema and infiltration by leukocytes as well as less positively immunostained cells for both TNF-α and IL-1ß in synovium) accompanied by a lack of toxicity as indicated by redox state and genotoxicity assays. Our results clearly indicate that the magnetic targeting of AuSPION suppresses joint edema and inflammation, cytokine expression as well as the redox imbalance, thereby contributing to an amelioration of arthritis severity in CIA rats. The results demonstrate for the first time the potentiality of AuSPION administration under a magnetic field as an attractive alternative for future treatments of rheumatic diseases.

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. We recruited professional motorcyclists and office workers from Porto Alegre, Brazil, between January and December 2016. Individual exposure to air pollutants was assessed by passive monitoring. Fingernail trace elements were determined by using inductively coupled plasma mass spectrometry. Oxidative stress biomarkers were quantified spectrophotometrically, and genotoxicity was evaluated by micronuclei assay. Individual exposure to NO2 and O3, trace element content (Sb, Pt, As, Cd, V, Mn, and Co), oxidative stress factors, and genetic damage were statistically higher in professional motorcyclists (p < 0.05). Moreover, NO2 and O3 levels showed very strong positive correlation with plasmatic lipid peroxidation (p < 0.001 and r = 0.8849 and 0.8995) and strong positive correlation with micronuclei frequency (p < 0.001 and r = 0.7683 and 0.7280). Results suggest that professional motorcyclists are at high risk due to long-term air pollution exposure, which implies in the onset of several harmful effects and worsening of pre-existent diseases.

Arsenic, cadmium, and mercury-induced hypertension: mechanisms and epidemiological findings.

Arsenic (As), cadmium (Cd), and mercury (Hg) are toxic elements widely distributed in the environment. Exposure to these elements was attributed to produce several acute and chronic illnesses including hypertension. The aim of this review is to provide a summary of the most frequently proposed mechanisms underlying hypertension associated with As, Cd, and Hg exposure including: oxidative stress, impaired nitric oxide (NO) signaling, modified vascular response to neurotransmitters and disturbed vascular muscle Ca2+ signaling, renal damage, and interference with the renin-angiotensin system. Due to the complexity of the vascular system, a combination rather than a singular mechanism needs to be considered. In addition, epidemiological findings showing the relationship between various biomarkers of metal exposure and hypertension are described. Given the complex etiology of hypertension, further epidemiological studies evaluating the roles of confounding factors such as age, gender, and life style are still necessary.

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 aim was to evaluate the effects of long-term Se supplementation upon systolic blood pressure (SBP) and redox status of rats exposed to sodium selenite. Male Wistar rats were exposed to 2 and 6 mg/L of sodium selenite in drinking water for 85 days. SBP and body weight were evaluated weekly; oxidative stress biomarkers were measured in blood or plasma; and Se levels were assessed in blood, plasma, kidney, and liver. Se supplementation (2 and 6 mg/L) induced significant increase in the SBP in rats from the 42nd day until the end of the study. This increase on SBP was not associated with significant changes in oxidative stress biomarkers. A significant increase in Se levels was found in whole blood, kidney, and liver from both groups of rats receiving Se supplementation when compared to control. Although the exact mechanisms underlying this augment in SBP are not clear, they are potentially related to other Se biological routes besides the synthesis of selenoproteins, such as GSH-Px. Due to the negative effects upon blood pressure, precautionary measures are advised, since the selling of supplements does not require a medical prescription.

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. Further, oxidative stress markers activity of glutathione peroxidase (GPx) and catalase (CAT) activity, as well as levels of reduced glutathione (GSH), malondialdehyde (MDA), and nitric oxide, were examined, and the comet assay was performed, using blood/plasma. Hg levels were measured in blood, brain, and kidneys of animals. Our results demonstrated that NA reduced adverse effects produced by MeHg. The mechanism underlying these effects appears to be related to the intrinsic antioxidant potential of NA. Considering the beneficial effects attributed to NA following MeHg exposure and that fish are the main source of both NA and MeHg, future studies need to evaluate the potential counteractive effect of NA against the adverse consequences of MeHg exposure in fish-eating populations.

Monitoring an outdoor smoking area by means of PM2.5 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 2.5 µm (PM2.5) levels, the pollen abortion assay, and trace elements accumulated in plant leaves in an outdoor smoking area of a hospital. For this, PM2.5 was measured by active monitoring with a real time aerosol monitor for 10 days. Eugenia uniflora trees were used for pollen abortion and accumulated element assays. Accumulated elements were also assessed in Tradescantia pallida leaves. The median concentration of PM2.5 in the smoking area in all days of monitoring was 66 versus 34 µg/m3 in the control area (P < 0.001). In addition, the elements Al, Cd, Cu, Ni, Pb, Rb, Sb, Se, and V in Tradescantia pallida and Al, Ba, Cr, Cu, Fe, Mg, Pb, and Zn in Eugenia uniflora were in higher concentration in the smoking area when compared to control area. Smoking area also showed higher rate of aborted grains (26.1 ± 10.7 %) compared with control (17.6 ± 4.5 %) (P = 0.003). Under the study conditions, vegetal biomonitoring proved to be an effective tool for assessing ETS exposure in outdoor areas. Therefore, vegetal biomonitoring of ETS could be a complement to conventional analyses and also proved to be a cheap and easy-handling tool to assess the risk of ETS exposure in outdoor areas.

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. Human kidney proximal tubular epithelial (HK2) cells were exposed for 24 h to thimerosal (0-2 µM), and assessed for cell viability, apoptosis, and cell proliferation; expression of proteins Bax, nuclear factor-κB subunits, and transforming growth factor-ß1 (TGFß1); mitochondrial health (JC-1, MitoTracker Red CMXRos); and fibronectin levels (enzyme-linked immunosorbent assay). Thimerosal diminished HK2 cell viability and mitosis, promoted apoptosis, impaired the mitochondrial permeability transition, enhanced Bax and TGFß1 expression, and augmented fibronectin secretion. This is the first report about kidney cell death and pro-fibrotic mechanisms promoted by thimerosal. Collectively, these in vitro results demonstrate that (1) thimerosal induces kidney epithelial cell apoptosis via upregulating Bax and the mitochondrial apoptotic pathway, and (2) thimerosal is a potential pro-fibrotic agent in human kidney cells. We suggest that new evidence on toxicity as well as continuous surveillance in terms of fibrogenesis is required concerning thimerosal use.