E-Cigarette Exposure During Fetal Development Alters Protein Transporters and Gene Expression Activity in Neural Pathways Associated With Obesity in Mice [Meeting Abstract]
Electronic cigarettes (E-cigs), battery-powered devices containing vegetable glycerin and propylene glycol (PG/VG) as humectants, along with nicotine and flavors, are the most commonly used nicotine product amongst adolescents and young adults. Despite the lack of safety data, pregnant cigarette smokers are also turning to e-cigs as a 'safer' smoking alternative. This study hypothesized that like cigarette smoking, maternal vaping during pregnancy increases the risk of childhood obesity in the offspring. Thus, C57BL/6 mice were exposed both prenatally (3h/d; 5d/wk for ~3-wk) and postnatally from PND 4-21 to e-cig aerosols (50:50 PG/VG) with and without nicotine (16 mg/mL) and alterations in transcriptional and inflammatory activity in hypothalamic metabolic pathways associated with obesity were investigated. At 1-mo-of-age, offspring from filtered air (FA) control and both treatment groups were sacrificed, the hypothalami collected and expression of transporters associated with obesity (i.e., Glucose 1,2,3,4, PPARgamma, and Leptin) analyzed by Western blot. Results here demonstrated a significant increase in glucose transporter 1-4 expression in both the PG/VG alone and PG/VG plus nicotine treatment groups compared to control levels. In addition, gene expression of PPARgamma, LepRb, MC4R, SLC2A1 were significantly increased (p<0.01) in these same 1-moold offspring compared to matched FA controls. Alternatively, no significant changes in AMPK and POMC expression was observed between and amongst treatment groups. These findings suggest that like traditional cigarettes, early life exposure to vaping aerosols (with and without nicotine) predispose the young offspring to obesity later in life via e-cig-induced alterations in the neural-obesity pathways
Per- and Polyfluoroalkyl substances (PFAS) in our environment-What's their story?
Longitudinal Impact of WTC Dust Inhalation on Rat Cardiac Tissue Transcriptomic Profiles
First responders (FR) exposed to the World Trade Center (WTC) Ground Zero air over the first week after the 9/11 disaster have an increased heart disease incidence compared to unexposed FR and the general population. To test if WTC dusts were causative agents, rats were exposed to WTC dusts (under isoflurane [ISO] anesthesia) 2 h/day on 2 consecutive days; controls received air/ISO or air only. Hearts were collected 1, 30, 240, and 360 d post-exposure, left ventricle total RNA was extracted, and transcription profiles were obtained. The data showed that differentially expressed genes (DEG) for WTC vs. ISO rats did not reach any significance with a false discovery rate (FDR) < 0.05 at days 1, 30, and 240, indicating that the dusts did not impart effects beyond any from ISO. However, at day 360, 14 DEG with a low FDR were identified, reflecting potential long-term effects from WTC dust alone, and the majority of these DEG have been implicated as having an impact on heart functions. Furthermore, the functional gene set enrichment analysis (GSEA) data at day 360 showed that WTC dust could potentially impact the myocardial energy metabolism via PPAR signaling and heart valve development. This is the first study showing that WTC dust could significantly affect some genes that are associated with the heart/CV system, in the long term. Even > 20 years after the 9/11 disaster, this has potentially important implications for those FR exposed repeatedly at Ground Zero over the first week after the buildings collapsed.
Building Environmental Health and Genomics Literacy among Healthcare Providers Serving Vulnerable Communities: An Innovative Educational Framework
This study addresses healthcare providers' knowledge deficits in environmental health and genetics, and primarily focuses on student nurses and nurses serving marginalized, low-income communities frequently exposed to environmental toxicants. Our approach to improve public health is unique, combining hands-on modeling exercises with case-based lessons in addition to three targeted 40 min lectures on toxicology. These lectures included the team's community-based environmental health research among Indigenous peoples of the U.S. The hands-on approach employed DNA and protein molecular models designed to demonstrate normal and dysfunctional molecules, as well as genetic variants in world populations. The models provided learners with visuals and an experience of "learning by doing." Increased awareness of the effects of environmental toxicants is the first step toward improving health care for exposed communities. We measured knowledge gains by pre- and post-tests among student nurses and nurses serving Native Americans living both in urban and rural areas of the U.S. (n = 116). The modeling lessons illustrated genetic variants in liver proteins common in Native peoples and their resulting health vulnerabilities. Participants were engaged and enthusiastic; and pre- and post-test results reported substantial knowledge gains and a greater understanding of genetic susceptibility (p < 0.0001). Our study demonstrates the utility of this framework across diverse populations and remote communities.
Long-Term Toxicity of E-Cigarette Whole Body Aerosol Exposure Using Cardiovascular Health and Pulmonary Changes in Mice as Persistent Outcomes [Meeting Abstract]
A contemporary review of electronic waste through the lens of inhalation toxicology
Inhalation is a significant route of exposure to toxic chemicals for electronic waste (e-waste) workers, especially for those whose activities take place in the informal sector. However, there remains a dearth of research on the health effects produced by the hazardous dismantling of e-waste and associated outcomes and biological mechanisms that occur as a result of inhalation exposure. This contemporary review highlights a number of the toxicological and epidemiological studies published on this topic to bring to light the many knowledge gaps that require further research, including inÂ vitro and ex vivo investigations to address the health outcomes and underlying mechanisms of inhaled e-waste-associated pulmonary disease.
Particulate matter and associated metals: A link with neurotoxicity and mental health
Particulate air pollution (PM) is a mixture of heterogenous components from natural and anthropogenic sources and contributes to a variety of serious illnesses, including neurological and behavioral effects, as well as millions of premature deaths. Ultrafine (PM0.1) and fine-size ambient particles (PM2.5) can enter the circulatory system and cross the blood-brain barrier or enter through the optic nerve, and then upregulate inflammatory markers and increase reactive oxygen species (ROS) in the brain. Toxic and neurotoxic metals such as manganese (Mn), zinc (Zn), lead (Pb), copper (Cu), nickel (Ni), and barium (Ba) can adsorb to the PM surface and potentially contribute to the neurotoxic effects associated with PM exposure. Epidemiological studies have shown a negative relationship between exposure to PM-associated Mn and neurodevelopment amongst children, as well as impaired dexterity in the elderly. Inhaled PM-associated Cu has also been shown to impair motor performance and alter basal ganglia in schoolchildren. This paper provides a brief review of the epidemiological and toxicological studies published over the last five years concerning inhaled PM, PM-relevant metals, neurobiology, and mental health outcomes. Given the growing interest in mental health and the fact that 91% of the world"™s population is considered to be exposed to unhealthy air, more research on PM and PM-associated metals and neurological health is needed for future policy decisions and strategic interventions to prevent public harm.
Plant-Derived Food Grade Substances (PDFGS) Active Against Respiratory Viruses: A Systematic Review of Non-clinical Studies [Review]
Pyridoxine deficiency modulates benzene inhalation-induced hematotoxicity associated with hepatic CYP2E1 activity in B6C3F1 mice
Pyridoxine is a co-factor in many enzymatic reactions and impacts of deficiency have been observed in affected populations. A possible modifying effect of pyridoxine deficiency on benzene toxicity was assessed in male B6C3F1 mice fed either a pyridoxine-deficient diet or a control diet. This treatment was combined with benzene inhalation exposure (100 ppm) or no benzene treatment. Pyridoxine-deficient mice exposed to 100 ppm benzene had significantly lower body, thymus and spleen weights. While total white blood cell counts, percentage of lymphocytes, hematocrit and hemoglobin levels were lower, the percentage of neutrophils was significantly higher in deficient and benzene-exposed mice compared to non-exposed controls. Hepatic CYP2E1 protein expression and activity in the deficient and exposed mice were also significantly higher compared to the non-exposed controls. A significant correlation between CYP2E1 activity and several hematological parameters was observed. These results demonstrated that pyridoxine deficiency significantly impacted benzene-induced hematotoxicity. Moreover, the observed agonistic effect of pyridoxinedeficiency and benzene inhalation exposure on CYP2E1 would seem to indicate an involvement of metabolism, but this needs to be further assessed.
Longitudinal impact on rat cardiac tissue transcriptomic profiles due to acute intratracheal inhalation exposures to isoflurane
Isoflurane (ISO) is a widely used inhalation anesthetic in experiments with rodents and humans during surgery. Though ISO has not been reported to impart long-lasting side effects, it is unknown if ISO can influence gene regulation in certain tissues, including the heart. Such changes could have important implications for use of this anesthetic in patients susceptible to heart failure/other cardiac abnormalities. To test if ISO could alter gene regulation/expression in heart tissues, and if such changes were reversible, prolonged, or late onset with time, SHR (spontaneously hypertensive) rats were exposed by intratracheal inhalation to a 97.5% air/2.5% ISO mixture on two consecutive days (2 hr/d). Control rats breathed filtered air only. On Days 1, 30, 240, and 360 post-exposure, rat hearts were collected and total RNA was extracted from the left ventricle for global gene expression analysis. The data revealed differentially-expressed genes (DEG) in response to ISO (compared to naÃ¯ve control) at all post-exposure timepoints. The data showed acute ISO exposures led to DEG associated with wounding, local immune function, inflammation, and circadian rhythm regulation at Days 1 and 30; these effects dissipated by Day 240. There were other significantly-increased DEG induced by ISO at Day 360; these included changes in expression of genes associated with cell signaling, differentiation, and migration, extracellular matrix organization, cell-substrate adhesion, heart development, and blood pressure regulation. Examination of consistent DEG at Days 240 and 360 indicated late onset DEG reflecting potential long-lasting effects from ISO; these included DEG associated with oxidative phosphorylation, ribosome, angiogenesis, mitochondrial translation elongation, and focal adhesion. Together, the data show acute repeated ISO exposures could impart variable effects on gene expression/regulation in the heart. While some alterations self-resolved, others appeared to be long-lasting or late onset. Whether such changes occur in all rat models or in humans remains to be investigated.