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ToxPoint: Using Multiomics to Bridge the Gap Between Electronic Cigarette Research and Disease Etiology
Avenbuan, Oyemwenosa N; Klein, Catherine B; Zelikoff, Judith T
PMID: 33259631
ISSN: 1096-0929
CID: 4734842
Prenatal Exposure to Electronic-Cigarette Aerosols Leads to Sex-Dependent Pulmonary Extracellular-Matrix Remodeling and Myogenesis in Offspring Mice
Wang, Qixin; Sundar, Isaac K; Blum, Jason L; Ratner, Jill R; Lucas, Joseph H; Chuang, Tsai-Der; Wang, Ying; Liu, Jie; Rehan, Virender K; Zelikoff, Judith T; Rahman, Irfan
Electronic-cigarette (e-cig) vaping is a serious concern, as many pregnant women who vape consider it safe. However, little is known about the harmful effects of prenatal e-cig exposure on adult offspring, especially on extracellular-matrix (ECM) deposition and myogenesis in the lungs of offspring. We evaluated the biochemical and molecular implications of maternal exposure during pregnancy to e-cig aerosols on the adult offspring of both sexes, with a particular focus on pulmonary ECM remodeling and myogenesis. Pregnant CD-1 mice were exposed to e-cig aerosols with or without nicotine, throughout gestation, and lungs were collected from adult male and female offspring. Compared with the air-exposed control group, female mice exposed to e-cig aerosols, with or without nicotine, demonstrated increased lung protein abundance of LEF-1 (lymphoid enhancer-binding factor 1), fibronectin, and E-cadherin, whereas altered E-cadherin and PPARγ (peroxisome proliferator-activated receptor γ) levels were observed only in males exposed to e-cig aerosols with nicotine. Moreover, lipogenic and myogenic mRNAs were dysregulated in adult offspring in a sex-dependent manner. PAI-1 (plasminogen activator inhibitor-1), one of the ECM regulators, was significantly increased in females exposed prenatally to e-cig aerosols with nicotine and in males exposed to e-cig aerosols compared with control animals exposed to air. MMP9 (matrix metalloproteinase 9), a downstream target of PAI-1, was downregulated in both sexes exposed to e-cig aerosols with nicotine. No differences in lung histology were observed among any of the treatment groups. Overall, adult mice exposed prenatally to e-cig aerosols could be predisposed to developing pulmonary disease later in life. Thus, these findings suggest that vaping during pregnancy is unsafe and increases the propensity for later-life interstitial lung diseases.
PMID: 32853043
ISSN: 1535-4989
CID: 4706992
Prenatal Exposure to Gutkha, a Globally Relevant Smokeless Tobacco Product, Induces Hepatic Changes in Adult Mice
Doherty Lyons, Shannon; Blum, Jason L; Hoffman-Budde, Carol; Tijerina, Pamela B; Fiel, M Isabel; J Conklin, Daniel; Gany, Francesca; Odin, Joseph A; Zelikoff, Judith T
Maternal exposures during pregnancy affect the onset and progression of adult diseases in the offspring. A prior mouse study indicated that maternal tobacco smoke exposure affects hepatic fibrosis in adult offspring. Gutkha, a broadly used smokeless tobacco (ST) product, is widely used by pregnant woman in many countries. The objective of this murine study was to evaluate whether oral maternal exposure to gutkha during pregnancy alters non-alcoholic fatty liver disease (NAFLD) in adult offspring: risk factors for the progression of NAFLD to cirrhosis in adults remain elusive. Buccal cavity 'painting' of pregnant mice with gutkha began on gestational days (GD) 2-4 and continued until parturition. Beginning at 12 weeks of age, a subset of offspring were transitioned to a high-fat diet (HFD). Results demonstrated that prenatal exposure to gutkha followed by an HFD in adulthood significantly increased the histologic evidence of fatty liver disease only in adult male offspring. Changes in hepatic fibrosis-related cytokines (interleukin (IL)-1b and IL-6) and in hepatic collagen mRNA expression were observed when comparing adult male offspring exposed to gutkha in utero to those not exposed. These findings indicate that maternal use of gutkha during pregnancy affects NAFLD in adult offspring in a sex-dependent manner.
PMID: 33126512
ISSN: 1660-4601
CID: 4655782
Impact on rats from acute intratracheal inhalation exposures to WTC dusts
Cohen, Mitchell D; Prophete, Colette; Horton, Lori; Sisco, Maureen; Park, Sung-Hyun; Lee, Hyun-Wook; Zelikoff, Judith; Chen, Lung-Chi
Background: Studies have revealed the increased incidence of health disorders in First Responders (FR) who were at Ground Zero over the initial 72 hr after the World Trade Center (WTC) collapses. Previous studies in rats exposed to WTC dusts using exposure scenarios that mimicked FR mouthbreathing showed exposure led to altered expression of genes whose products could be involved in lung ailments. Nevertheless, it was uncertain if repeated exposures (as occurred in earliest days post-disaster) might have given rise to long-term changes in the lungs/other organs, in white blood cell (WBC) profiles, and/or systemic expression of select (mostly immune-related) proteins.Methods: To examine this, rats were exposed on 2 consecutive days (2 hr/d, intratracheal inhalation) to WTC dusts and then examined over a 1-yr period thereafter. At select times post-exposure, organ (lung, heart, liver, kidney, spleen) weights, WBC profiles, and blood levels of a variety of proteins were evaluated.Results: The study showed that over the 1-yr period, there were nominal effects on organ weights (absolute, index) as a result of the dust exposures. There were significant changes (relative to in naïve rats) in WBC profiles, with exposed rats having increased monocyte-macrophage and decreased lymphocyte percentages. The study also found that dust exposure led to significant systemic increases in many proteins, including MCP-1, RANTES, MMP-9, RAGE, and Galectin-3.Conclusions: These results provide further support for our longstanding hypothesis that the WTC dusts could potentially have acted as direct inducers of many of the health effects that have been seen in the exposed FR.
PMID: 32448006
ISSN: 1091-7691
CID: 4510282
The Ramapough Lunaape Nation: Facing Health Impacts Associated with Proximity to a Superfund Site
Meltzer, Gabriella; Avenbuan, Oyemwenosa; Wu, Fen; Shah, Krina; Chen, Yu; Mann, Vincent; Zelikoff, Judith T
This study aimed to evaluate self-reported exposure to the Ringwood Mines/Landfill Superfund Site in relation to chronic health outcomes among members of the Ramapough Lunaape Turtle Clan nation and other local residents of Ringwood, New Jersey. Community surveys on personal exposure to the nearby Superfund site, self-reported health conditions, and demographics were conducted with 187 members of the Ramapough Lunaape Turtle Clan Nation and non-Native Americans residing in Ringwood, New Jersey from December 2015 to October 2016. Multiple logistic regression was performed to assess the association between ethnicity and a Superfund site exposure score developed for this study, as well as between exposure score and several chronic health conditions. Native Americans were 13.84 times (OR 13.84; 95% CI 4.32, 44.37) more likely to face exposure opportunities to Superfund sites as compared to non-Native Americans in the same New Jersey borough. For the entire surveyed cohort, increased Superfund site exposure routes was significantly associated with bronchitis (OR 4.10; 95% CI 1.18, 14.23). When the analyses were restricted to Native Americans, the association between self-reported Superfund site exposure and bronchitis remained significant (OR 17.42; 95% CI 1.99, 152.45). Moreover, the association between greater exposure score and asthma in this same population also reached statistical significance (OR 6.16; 95% CI 1.38, 27.49). This pilot study demonstrated a significant association between being a Ringwood resident of Native American ethnicity and self-declared opportunities for Superfund site exposure. It also showed a strong association between self-reported Superfund site exposure and the prevalence of bronchitis and asthma.
PMID: 32447544
ISSN: 1573-3610
CID: 4465862
Review: Woodsmoke and emerging issues
Avenbuan, Oyemwenosa N.; Zelikoff, Judith T.
Wood is a type of biomass commonly burnt as a means of energy. When burnt, it releases harmful components linked to adverse health outcomes. In the scientific community toxicologists and epidemiologists continue to consider the individual components of woodsmoke "” such as particulate matter and polycyclic aromatic hydrocarbons "” as a way to better understand the relationship between inhaled woodsmoke and acute and chronic disease. In recent years, research focus has shifted toward the underlying mechanisms that could be associated with long-term health consequences. Alongside this research, novel studies in molecular toxicology that examine the impacts of woodsmoke could provide a link between woodsmoke and telomere length. Such studies could provide scientists with a better understanding on how woodsmoke leads to chronic diseases. As researchers from various disciplines come together to work on this complex and widespread issue, hope emerges to reduce the morbidity and mortality associated with this global air pollutant.
SCOPUS:85083327702
ISSN: 2468-2020
CID: 4421202
Neuroinflammatory and Behavioral Outcomes Measured in Adult Offspring of Mice Exposed Prenatally to E-Cigarette Aerosols
Church, Jamie S; Chace-Donahue, Fiona; Blum, Jason L; Ratner, Jill R; Zelikoff, Judith T; Schwartzer, Jared J
BACKGROUND:In an effort to decrease the rates of smoking conventional tobacco cigarettes, electronic cigarettes (e-cigarettes) have been proposed as an effective smoking cessation tool. However, little is known about their toxicological impacts. This is concerning given that e-cigarette use is perceived as less harmful than conventional tobacco cigarettes during pregnancy for both the mother and fetus. OBJECTIVE:The goal of this study was to test the neurodevelopmental consequences of maternal e-cigarette use on adult offspring behavior and neuroimmune outcomes. METHODS: RESULTS: DISCUSSION/CONCLUSIONS:These findings support previous adverse findings of e-cigarette exposure on neurodevelopment in a mouse model and provide substantial evidence of persistent adverse behavioral and neuroimmunological consequences to adult offspring following maternal e-cigarette exposure during pregnancy. https://doi.org/10.1289/EHP6067.
PMID: 32293200
ISSN: 1552-9924
CID: 4401362
Neurotoxicity of e-cigarettes
Ruszkiewicz, Joanna A; Zhang, Ziyan; Gonçalves, Filipe Marques; Tizabi, Yousef; Zelikoff, Judith T; Aschner, Michael
It appears that electronic cigarettes (EC) are a less harmful alternative to conventional cigarette (CC) smoking, as they generate substantially lower levels of harmful carcinogens and other toxic compounds. Thus, switching from CC to EC may be beneficial for smokers. However, recent accounts of EC- or vaping-associated lung injury (EVALI) has raised concerns regarding their adverse health effects. Additionally, the increasing popularity of EC among vulnerable populations, such as adolescents and pregnant women, calls for further EC safety evaluation. In this state-of-the-art review, we provide an update on recent findings regarding the neurological effects induced by EC exposure. Moreover, we discuss possible neurotoxic effects of nicotine and numerous other chemicals which are inherent both to e-liquids and EC aerosols. We conclude that in recognizing pertinent issues associated with EC usage, both government and scientific researchers must address this public health issue with utmost urgency.
PMID: 32145355
ISSN: 1873-6351
CID: 4341012
A Systematic Review of Environmental Health Outcomes in Selected American Indian and Alaska Native Populations
Meltzer, Gabriella Y; Watkins, Beverly-Xaviera; Vieira, Dorice; Zelikoff, Judith T; Boden-Albala, Bernadette
BACKGROUND:Economic and social marginalization among American Indians and Alaska Natives (AI/ANs) results in higher chronic disease prevalence. Potential causal associations between toxic environmental exposures and adverse health outcomes within AI/AN communities are not well understood. OBJECTIVES/OBJECTIVE:This review examines epidemiological literature on exposure to toxicants and associated adverse health outcomes among AI/AN populations. METHODS:PubMed, Embase, Cochrane, Environment Complete, Web of Science Plus, DART, and ToxLine were searched for English-language articles. The following data were extracted: lead author's last name, publication year, cohort name, study location, AI/AN tribe, study initiation and conclusion, sample size, primary characteristic, environmental exposure, health outcomes, risk estimates, and covariates. RESULTS:About 31 articles on three types of environmental exposures met inclusion criteria: persistent organic pollutants (POPs), heavy metals, and open dumpsites. Of these, 17 addressed exposure to POPs, 10 heavy metal exposure, 2 exposure to both POPs and heavy metals, and 2 exposure to open dumpsites. Studies on the Mohawk Nation at Akwesasne; Yupik on St. Lawrence Island, Alaska; Navajo Nation; Gila River Indian Community; Cheyenne River Sioux; 197 Alaska Native villages; and 13 tribes in Arizona, Oklahoma, North Dakota, and South Dakota that participated in the Strong Heart Study support associations between toxicant exposure and various chronic conditions including cardiovascular conditions, reproductive abnormalities, cancer, autoimmune disorders, neurological deficits, and diabetes. DISCUSSION/CONCLUSIONS:The complex interplay of environmental and social factors in disease etiology among AI/ANs is a product of externally imposed environmental exposures, systemic discrimination, and modifiable risk behaviors. The connection between environmental health disparities and adverse health outcomes indicates a need for further study.
PMID: 31974734
ISSN: 2196-8837
CID: 4274012
Community health perceptions and human environmental exposure to chromium contamination in a small New Jersey City
Doherty, Lyons Sp; Bari, S; Gany, F; Leng, J; Duch, T; Reveille, D; Morris, J S; Hernandez, M; Nadas, A; Costa, M; Zelikoff, J T
Following a 1983 chromic acid (hexavalent chromium [CrVI]) spill from a Garfield, NJ electroplating plant, CrVI-contaminated water was found in a local firehouse basement in 1993. An ATSDR public health advisory was issued for the plant site in 2010, and from 2008-2015, fourteen residential properties have required remediation to address CrVI-contaminated dust in the basements. As part of the Community Outreach and Engagement Core of the NYU NIEHS Center, seventytwo Garfield residents aged 18-65 years, participated in a community survey with the goal of identifying concerns related to environmental and community health. Thirty-two percent responded that they 'didn't know' if they were exposed to chemicals or pollutants where they live. This finding suggests a limited awareness of environmental chemical exposures, chromium contamination and/or potential exposure to CrVI. Furthermore, toenail clippings were collected from forty-seven Garfield residents and analyzed for total chromium levels to assess potential long-term exposure. On average, residents living on/inside the contaminated plume area had higher total chromium levels in their toenail clippings than residents living outside the plume area. However, chromium levels for all participants were within the range of historical normal. This study highlights the value of partnerships between environmentally-impacted community's and academic scientists working together to identify potential contaminant exposures and address public health concerns through research and environmental health education.
PMCID:8188903
PMID: 34113778
ISSN: 2516-7073
CID: 5046662