Bioavailability of Inhaled Or Ingested PFOA Adsorbed To House Dust

Indoor environments may impact human health due to chemical pollutants in the indoor air and house dust. This study aimed at comparing the bioavailability and distribution of PFOA following both an inhalation and an oral exposure to PFOA coated house dust in rats. In addition, extractable organofluorine (EOF) was measured in different tissue samples to assess any potential influence of other organofluorine compounds in the experimental house dust. Blood samples were collected at sequential time points after exposure and at the time of termination; lung, liver and kidney were collected for quantification of PFOA and EOF. The concentration of PFOA in plasma increased rapidly in both exposure groups attaining a Cmax at 3 h post exposure. The Cmax following inhalation was four times higher compared to oral exposures. At 48 h post exposure, the levels of PFOA in plasma, liver and kidney were twice as high from inhalation exposures. This shows that PFOA is readily bioavailable and has a rapid systemic distribution following an inhalation- or oral exposure to house dust coated with PFOA. The proportion of PFOA to EOF corresponded to approximately 54-68% and >80% in plasma and tissues, respectively. The mass balance between EOF and target PFOA indicate that there might be other unknown PFAS precursor and/or fluorinated compounds that co-existed in the house dust sample that might have accumulated in rats.

Effect of a Sub-Chronic Oral Exposure of Broccoli (Brassica oleracea L. Var. Italica) By-Products Flour on the Physiological Parameters of FVB/N Mice: A Pilot Study

Brassica by-products are a source of natural bioactive molecules such as glucosinolates and isothiocyanates, with potential applications in the nutraceutical and functional food industries. However, the effects of oral sub-chronic exposure to broccoli by-product flour (BF) have not yet been evaluated. The objective of this pilot study was to analyse the effects of BF intake in the physiological parameters of FVB/N mice fed a 6.7% BF-supplemented diet for 21 days. Glucosinolates and their derivatives were also quantified in plasma and urine. BF supplementation significantly decreased (p < 0.05) the accumulation of perirenal adipose tissue. Furthermore, mice supplemented with BF showed significantly lower (p < 0.01) microhematocrit values than control animals, but no impact on the general genotoxicological status nor relevant toxic effects on the liver and kidney were observed. Concerning hepatic and renal antioxidant response, BF supplementation induced a significant increase (p < 0.05) in the liver glutathione S-transferase (GST) levels. In BF-supplemented mice, plasma analysis revealed the presence of the glucosinolates glucobrassicin and glucoerucin, and the isothiocyanates sulforaphane and indole-3-carbinol. Overall, these results show that daily intake of a high dose of BF during three weeks is safe, and enables the bioavailability of beneficial glucosinolates and isothiocyanates. These results allow further testing of the benefits of this BF in animal models of disease, knowing that exposure of up to 6.7% BF does not present relevant toxicity.

Features of bioaccumulation and toxic effects of copper (II) oxide nanoparticles under the oral route of intake into the body

Introduction. Active use in various spheres of economic activity and the large-scale nature of production determine the relevance of studying the effects of copper (II) oxide nanoparticles (CuO NPs) on the body during the oral route of intake. Material and methods. Particle size was determined by scanning electron microscopy and dynamic laser light scattering; specific surface area - Brunauer, Emmett and Teller; total pore volume - Barrett, Joyner and Khalenda. Acute oral toxicity of CuO NPs was studied in Wistar rats in accordance with GOST 32644-2014, multiple oral toxicity was studied by the Lim method. After repeated exposure, the biochemical and hematological parameters of the blood, the concentration of copper in the organs, and pathomorphological changes in the tissues of the organs were determined. Results. The size of CuO NPs in the composition of the native powder was 45.86 nm, in the aqueous suspension - 307.40 nm, the specific surface area was 17.70 m2/g, and the total pore volume was 0.056 cm3/g. According to the results of a single oral exposure, the LD50 value was > 2000 mg / kg body weight, which corresponds to 3 (GOST 12.1.007-76) and 4 (GOST 32644-2014) hazard classes. With repeated oral exposure, an increase in the levels of activity of ALT, AST, ALP, LDH, amylase, AOA and MDA was noted; the relative number of segmented neutrophils is increased, the number of leukocytes is increased, the relative number of lymphocytes is reduced. The concentration of copper under the action of NPs increases in the lungs, liver, stomach, intestines, kidneys, brain and blood. Pathomorphological changes in the tissues of the liver, kidneys, stomach, small and large intestines and lungs were established. Conclusion. The results obtained prove the presence of toxic properties of CuO NPs and can be used in the development of preventive measures for workers and consumers in contact with products containing CuO NPs.

Gastrointestinal motility and Intestinal structure following oral exposure to acrylamide in Wistar rats

Introduction: Acrylamide, a byproduct of the cooking process, has been reported to be a toxicant with likely carcinogenic properties. Its impairment of gastric function has been previously reported. In this study its effects on gastrointestinal motility and intestinal structure was investigated in male Wistar rats.Methods: Forty-five rats (120-180g) were divided into 3 equal groups (n=15) and treated p.o with either 0.2ml distilled-water, or acrylamide (7.5mg/kg and 15mg/kg respectively) for 28days. Thereafter, gastric emptying and intestinal motility was assessed. Intestinal structure (duodenum, jejunum and ileum), mucosal and intestinal cell counts were evaluated using histological techniques.Results: Gastric emptying and intestinal transit time increased (p<0.05) in the experimental (acrylamidetreated; 7.5mg/kg and 15mg/kg) groups compared to control. Mucosal cell counts (duodenum, jejunum and ileum) and ileum intestinal cell counts (p<0.05) were reduced in the experimental groups compared to control. Compared to control, duodenal samples of the experimental groups showed severe coagulative necrosis and sloughing off of the villi, luminal filling with necrotic debris, disruption and necrosis of the crypts of Lieberkühn, moderate polymorphonuclear cell infiltration and vascular congestion. These pathologies albeit with less severity were also observed in the jejunum and ileum of acrylamide treated groups.Conclusion: Increased oral exposure to acrylamide impairs gastric emptying, intestinal motility, mucus secretion and compromises digestive and absorptive functions of the small intestines, especially the duodenum. These observations may be ascribed to acrylamide-induced impaired neuronal signaling, autonomic neuropathy, oxidative stress, inflammation and cell necrosis. Keywords: Acrylamide, gastrointestinal tract, gastric emptying, intestinal motility, small intestines

Sub-chronic oral exposure of tungsten induces markers of kidney injury

Tungsten is a naturally occurring transition element used in a broad range of applications. As a result of its extensive use, we are increasingly exposed to tungsten from our environment, including potable water, since tungsten can become bioaccessible in ground sources. The kidneys are particularly susceptible to tungsten exposure as this is the main site for tungsten excretion. In this study, we investigated the prolonged effects of tungsten on the kidneys and how this may impact injury and function. When mice were exposed to tungsten in their drinking water for 1-month, kidney function had not significantly changed. Following 3-month exposure, mice were presented with deterioration in kidney function as determined by serum and urine creatinine levels. During 3-months of tungsten exposure, murine kidneys demonstrated significant increases in the myofibroblast marker ⍺SMA, and extracellular matrix products: fibronectin, collagen, and matricellular proteins. In addition, Masson's trichrome and H&E staining revealed an increase in fibrotic tissue and vacuolization of tubular epithelial cells, respectively, from kidneys of tungsten-treated mice, indicative of renal injury. In vitro treatment of kidney fibroblasts with tungsten led to increased proliferation and upregulation of Transforming Growth Factor Beta 1 (TGFβ1), which was consistent with the appearance of fibroblast-to-myofibroblast transition (FMT) markers. Our data suggest that continuous exposure to tungsten impairs kidney function that may lead to the development of chronic kidney disease (CKD).

Effect of Oral Applied Lead Acetate on the Expression of Caspase-3 on Antral Granulosa Cells and Histopathology of Ovary in Female Wistar Rat (Rattus Norvegicus) Ovaries

Background: Lead exposure affects several human organs, including the reproductive organ. Aims: This research aims to prove the effect of oral applied lead acetate on the expression of caspase-3 in antral granulosa cells, the diameter of the tertiary follicle, and the amount of follicle atresia inside ovaries. Methods: Twenty-four female Wistar rats (Rattus norvegicus) are classified into 4 groups. Group 1 consists of 6 rats acting as control groups. Group 2, 3, and 4 each consist of 6 rats receiving daily oral lead acetate of 30 ppm, 100 ppm, and 300 ppm in dose, respectively. The experiment will be conducted in 30 days. The rats are then dissected, and the weight of ovaries are measured. The expression of caspase-3 is assessed using immunohistochemistry, while the diameter of tertiary follicles and the amount of follicle atresia are both observed using Hematoxylin-Eosin stain. Results: Oral administration of lead acetate significantly decreased the weight of ovaries. Oral exposure of lead enhances the expression of caspase-3 in antral granulosa cells of all experiment groups, especially in the 300 ppm group. It significantly shrinks tertiary follicles' diameter in rats' ovaries to 100 ppm and 300 ppm groups. It also increases the amount of follicle atresia in the 300 ppm group. Conclusion: Oral exposure of lead enhances the expression of caspase 3 in antral granulosa cells at 300 ppm, shrinks the diameter of tertiary follicles at 100 ppm and 300 ppm doses, and increases the amount of follicle atresia at 300 ppm dose.

Pathogenesis of wild-type-like rhesus cytomegalovirus strains following oral exposure of immune-competent rhesus macaques

Rhesus cytomegalovirus (RhCMV) infection of rhesus macaques ( Macaca mulatta ) is a valuable nonhuman primate model of human CMV (HCMV) persistence and pathogenesis. In vivo studies predominantly use tissue culture-adapted variants of RhCMV that contain multiple genetic mutations compared to wild-type (WT) RhCMV. In many studies, animals have been inoculated by non-natural routes ( e.g. , subcutaneous, intravenous) that do not recapitulate disease progression via the normative route of mucosal exposure. Accordingly, the natural history of RhCMV would be more accurately reproduced by infecting macaques with strains of RhCMV that reflect the WT genome using natural routes of mucosal transmission. Herein, we tested two WT-like RhCMV strains, UCD52 and UCD59, and demonstrated that systemic infection and frequent, high-titer viral shedding in bodily fluids occurred following oral inoculation. RhCMV disseminated to a broad range of tissues, including the central nervous system and reproductive organs. Commonly infected tissues included the thymus, spleen, lymph nodes, kidneys, bladder, and salivary glands. Histological examination revealed prominent nodular hyperplasia in spleens and variable levels of lymphoid lymphofollicular hyperplasia in lymph nodes. One of six inoculated animals had limited viral dissemination and shedding, with commensurately weak antibody responses to RhCMV antigens. These data suggest that long-term RhCMV infection parameters might be restricted by local innate factors and/or de novo host immune responses in a minority of primary infections. Together, we have established an oral RhCMV infection model that mimics natural HCMV infection. The virological and immunological parameters characterized in this study will greatly inform HCMV vaccine designs for human immunization. IMPORTANCE Human cytomegalovirus (HCMV) is globally ubiquitous with high seroprevalence rates in all communities. HCMV infections can occur vertically following mother-to-fetus transmission across the placenta and horizontally following shedding of virus in bodily fluids in HCMV infected hosts and subsequent exposure of susceptible individuals to virus-laden fluids. Intrauterine HCMV has long been recognized as an infectious threat to fetal growth and development. Since vertical HCMV infections occur following horizontal HCMV transmission to the pregnant mother, the nonhuman primate model of HCMV pathogenesis was used to characterize the virological and immunological parameters of infection following primary mucosal exposures to rhesus cytomegalovirus.

Brominated flame retardant TBPH induced oxidative damage and reduced the expression of memory-related proteins in mice, with no discernable impairment of learning and memory

Bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH) is one of the new brominated flame retardants with adverse neurobehavioral potential. These flame retardants are often added to household furnishings where children would come into contact with them. This study explores whether oral exposure to TBPH for 28 days would impair neurobehavioral function in mice and the role of curcumin (CUR) in this process. CUR is a natural antioxidant and is thought to be of use in the treatment of neurological toxicity due to its neuroprotective effects. Learning and memory of mice exposed to TBPH was investigated using the Morris water maze. Levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) were determined to assess oxidative damage. Western blot was used to detect the expression of glucose-regulated protein 78-kDa (GRP78), PKR-like ER kinase (PERK), and C/EBP homologous protein (CHOP) in the hippocampus. End-point effects were evaluated through observing post-synaptic density protein-95 (PSD-95), brain-derived neurotrophic factor (BDNF), and phosphorylated cAMP response element binding protein (p-CREB). Although TBPH exposure alone does not impair learning and memory, oxidative stress markers and endoplasmic reticulum stress–associated proteins were adversely affected in exposed mice. TBPH could significantly decrease the levels of BDNF, p-CREB, and PSD-95 in the hippocampus, and these TBPH-induced neurotoxic effects were attenuated by CUR. These findings provide further understanding of the neurotoxic effects of TBPH and the protective effect of CUR on TBPH exposure.

Protective Role of Flavonoids against Intestinal Pro-Inflammatory Effects of Silver Nanoparticles

Silver nanoparticles (AgNP) have been increasingly incorporated into food-related and hygiene products for their unique antimicrobial and preservative properties. The consequent oral exposure may then result in unpredicted harmful effects in the gastrointestinal tract (GIT), which should be considered in the risk assessment and risk management of these materials. In the present study, the toxic effects of polyethyleneimine (PEI)-coated AgNP (4 and 19 nm) were evaluated in GIT-relevant cells (Caco-2 cell line as a model of human intestinal cells, and neutrophils as a model of the intestinal inflammatory response). This study also evaluated the putative protective action of dietary flavonoids against such harmful effects. The obtained results showed that AgNP of 4 and 19 nm effectively induced Caco-2 cell death by apoptosis with concomitant production of nitric oxide, irrespective of the size. It was also observed that AgNP induced human neutrophil oxidative burst. Interestingly, some flavonoids, namely quercetin and quercetagetin, prevented the deleterious effects of AgNP in both cell types. Overall, the data of the present study provide a first insight into the promising protective role of flavonoids against the potentially toxic effects of AgNP at the intestinal level.