Publications by authors named "Zakia Perveen"

10 Publications

  • Page 1 of 1

Effects of Chronic Secondhand Smoke (SHS) Exposure on Cognitive Performance and Metabolic Pathways in the Hippocampus of Wild-Type and Human Tau Mice.

Environ Health Perspect 2021 May 19;129(5):57009. Epub 2021 May 19.

Department of Basic Medical Sciences, Western University of Health Sciences, College of Osteopathic Medicine of the Pacific Northwest, Lebanon, Oregon, USA.

Background: Exposure to secondhand smoke (SHS) is a risk factor for developing sporadic forms of sporadic dementia. A human tau (htau) mouse model is available that exhibits age-dependent tau dysregulation, neurofibrillary tangles, neuronal loss, neuroinflammation, and oxidative stress starting at an early age (3-4 months) and in which tau dysregulation and neuronal loss correlate with synaptic dysfunction and cognitive decline.

Objective: The goal of this study was to assess the effects of chronic SHS exposure (10 months' exposure to ) on behavioral and cognitive function, metabolism, and neuropathology in mice.

Methods: Wild-type (WT) and htau female and male mice were exposed to SHS (90% side stream, 10% main stream) using the SCIREQ® inExpose™ system or air control for 168 min per day, for 312 d, 7 d per week. The exposures continued during the days of behavioral and cognitive testing. In addition to behavioral and cognitive performance and neuropathology, the lungs of mice were examined for pathology and alterations in gene expression.

Results: Mice exposed to chronic SHS exposure showed the following genotype-dependent responses: ) lower body weights in WT, but not htau, mice; ) less spontaneous alternation in WT, but not htau, mice in the Y maze; ) faster swim speeds of WT, but not htau, mice in the water maze; ) lower activity levels of WT and htau mice in the open field; ) lower expression of brain PHF1, TTCM1, , and HSP90 protein levels in WT male, but not female, mice; and ) more profound effects on hippocampal metabolic pathways in WT male than female mice and more profound effects in WT than htau mice.

Discussion: The brain of WT mice, in particular WT male mice, might be especially susceptible to the effects of chronic SHS exposure. In WT males, independent pathways involving ascorbate, flavin adenine dinucleotide, or palmitoleic acid might contribute to the hippocampal injury following chronic SHS exposure. https://doi.org/10.1289/EHP8428.
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http://dx.doi.org/10.1289/EHP8428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132614PMC
May 2021

Sub-ohm vaping increases the levels of carbonyls, is cytotoxic, and alters gene expression in human bronchial epithelial cells exposed at the air-liquid interface.

Respir Res 2020 Nov 19;21(1):305. Epub 2020 Nov 19.

Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, 1909 Skip Bertman Drive, Baton Rouge, LA, 70803, USA.

Background: Exposure to electronic-cigarette (e-cig) aerosols induces potentially fatal e-cig or vaping-associated lung injury (EVALI). The cellular and molecular mechanisms underlying these effects, however, are unknown. We used an air-liquid interface (ALI) in vitro model to determine the influence of two design characteristics of third-generation tank-style e-cig devices-resistance and voltage-on (1) e-cig aerosol composition and (2) cellular toxicity.

Methods: Human bronchial epithelial cells (H292) were exposed to either butter-flavored or cinnamon-flavored e-cig aerosols at the ALI in a Vitrocell exposure system connected to a third-generation e-cig device. Exposures were conducted following a standard vaping topography profile for 2 h per day, for 1 or 3 consecutive days. 24 h after ALI exposures cellular and molecular outcomes were assessed.

Results: We found that butter-flavored e-cig aerosol produced under 'sub-ohm' conditions (< 0.5 Ω) contains high levels of carbonyls (7-15 μg/puff), including formaldehyde, acetaldehyde and acrolein. E-cig aerosol produced under regular vaping conditions (resistance > 1 Ω and voltage > 4.5 V), contains lower carbonyl levels (< 2 μg/puff). We also found that the levels of carbonyls produced in the cinnamon-flavored e-cig aerosols were much lower than that of the butter-flavored aerosols. H292 cells exposed to butter-flavored or cinnamon-flavored e-cig aerosol at the ALI under 'sub-ohm' conditions for 1 or 3 days displayed significant cytotoxicity, decreased tight junction integrity, increased reactive oxygen species production, and dysregulated gene expression related to biotransformation, inflammation and oxidative stress (OS). Additionally, the cinnamon-flavored e-cig aerosol induced pro-oxidant effects as evidenced by increases in 8-hydroxy-2-deoxyguanosine protein levels. Moreover, we confirmed the involvement of OS as a toxicity process for cinnamon-flavored e-cig aerosol by pre-treating the cells with N-acetyl cysteine (NAC), an antioxidant that prevented the cells from the OS-mediated damage induced by the e-cig aerosol.

Conclusion: The production of high levels of carbonyls may be flavor specific. Overall, inhaling e-cig aerosols produced under 'sub-ohm' conditions is detrimental to lung epithelial cells, potentially via mechanisms associated with OS. This information could help policymakers take the necessary steps to prevent the manufacturing of sub-ohm atomizers for e-cig devices.
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http://dx.doi.org/10.1186/s12931-020-01571-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678293PMC
November 2020

Electronic-Cigarette Vehicles and Flavoring Affect Lung Function and Immune Responses in a Murine Model.

Int J Mol Sci 2020 Aug 21;21(17). Epub 2020 Aug 21.

Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA.

The use of electronic nicotine delivery systems (ENDS), also known as electronic-cigarettes (e-cigs), has raised serious public health concerns, especially in light of the 2019 outbreak of e-cig or vaping product use-associated acute lung injury (EVALI). While these cases have mostly been linked to ENDS that contain vitamin E acetate, there is limited research that has focused on the chronic pulmonary effects of the delivery vehicles (i.e., without nicotine and flavoring). Thus, we investigated lung function and immune responses in a mouse model following exposure to the nearly ubiquitous e-cig delivery vehicles, vegetable glycerin (VG) and propylene glycol (PG), used with a specific 70%/30% ratio, with or without vanilla flavoring. We hypothesized that mice exposed sub-acutely to these e-cig aerosols would exhibit lung inflammation and altered lung function. Adult female C57BL/6 mice ( = 11-12 per group) were exposed to filtered air, 70%/30% VG/PG, or 70%/30% VG/PG with a French vanilla flavoring for 2 h a day for 6 weeks. Prior to sacrifice, lung function was assessed. At sacrifice, broncho-alveolar lavage fluid and lung tissue were collected for lipid mediator analysis, flow cytometry, histopathology, and gene expression analyses. Exposures to VG/PG + vanilla e-cig aerosol increased lung tidal and minute volumes and tissue damping. Immunophenotyping of lung immune cells revealed an increased number of dendritic cells, CD4+ T cells, and CD19+ B cells in the VG/PG-exposed group compared to air, irrespective of the presence of vanilla flavoring. Quantification of bioactive lung lipids demonstrated a >3-fold increase of 2-arachidonoylglycerol (2-AG), an anti-inflammatory mediator, and a 2-fold increase of 12-hydroxyeicosatetraenoic acid (12-HETE), another inflammatory mediator, following VG/PG exposure, with or without vanilla flavoring. This suggests that e-cig aerosol vehicles may affect immunoregulatory molecules. We also found that the two e-cig aerosols dysregulated the expression of lung genes. Ingenuity Pathway Analysis revealed that the gene networks that are dysregulated by the VG/PG e-cig aerosol are associated with metabolism of cellular proteins and lipids. Overall, our findings demonstrate that VG and PG, the main constituents of e-liquid formulations, when aerosolized through an e-cig device, are not harmless to the lungs, since they disrupt immune homeostasis.
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http://dx.doi.org/10.3390/ijms21176022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504509PMC
August 2020

In utero exposures to electronic-cigarette aerosols impair the signaling during mouse lung development.

Am J Physiol Lung Cell Mol Physiol 2020 04 21;318(4):L705-L722. Epub 2020 Feb 21.

Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana.

Currently, more than 9 million American adults, including women of childbearing age, use electronic-cigarettes (e-cigs). Further, the prevalence of maternal vaping now approaching 10% is similar to that of maternal smoking. Little, however, is known about the effects of fetal exposures to nicotine-rich e-cig aerosols on lung development. In this study, we assessed whether in utero exposures to e-cig aerosols compromised lung development in mice. A third-generation e-cig device was used to expose pregnant BALB/c mice by inhalation to 36 mg/mL of nicotine cinnamon-flavored e-cig aerosols for 14-31 days. This included exposures for either 12 days before mating plus during gestation (preconception groups) or only during gestation (prenatal groups). Respective control mice were exposed to filtered air. Subgroups of offspring were euthanized at birth or at 4 wk of age. Compared with respective air-exposed controls, both preconception and prenatal exposures to e-cig aerosols significantly decreased the offspring birth weight and body length. In the preconception group, 7 inflammation-related genes were downregulated, including 4 genes common to both dams and fetuses, denoting an e-cig immunosuppressive effect. Lung morphometry assessments of preconception e-cig-exposed offspring showed a significantly increased tissue fraction at birth. This result was supported by the downregulation of 75 lung genes involved in the signaling, which is essential to lung organogenesis. Thus, our data indicate that maternal vaping impairs pregnancy outcomes, alters fetal lung structure, and dysregulates the signaling. This study provides experimental evidence for future regulations of e-cig products for pregnant women and developmentally vulnerable populations.
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http://dx.doi.org/10.1152/ajplung.00408.2019DOI Listing
April 2020

Sex-specific lung functional changes in adult mice exposed only to second-hand smoke in utero.

Respir Res 2017 06 27;18(1):104. Epub 2017 Jun 27.

Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Skip Bertman Drive, Baton Rouge, 70803, LA, USA.

Background: An increasing number of epidemiological and experimental studies have associated exposure to second-hand smoke (SHS) during pregnancy with adverse outcomes in newborns. As we have previously shown in mice, in utero exposure to SHS at critical stages of fetal development, results in altered lung responses and increased disease susceptibility upon re-exposure to irritants (SHS or ovalbumin) in adulthood. In this study, we asked whether the in utero SHS exposure alone is sufficient to alter lung structure and function in adult mice.

Methods: Pregnant BALB/c mice were exposed from days 6 to 19 of pregnancy to 10 mg/m of SHS or HEPA-filtered air. Male and female offspring (n = 13-15/group) were sacrificed at 15 weeks of age. We measured lung function with non-invasive and invasive methods, performed lung morphometric analysis on trichrome-stained lung tissue samples, and assessed lung gene expression via RNA sequencing and protein assays.

Results: In utero SHS exposure significantly increased mean linear intercept and decreased the surface area per unit volume of the lungs in both males and females, indicating perturbation in alveolar developmental processes. Tidal volume, minute volume and inspiratory capacity were significantly decreased compared with the controls only in male mice exposed in utero to SHS, suggesting that males are more sensitive than females to an SHS insult during lung development. This also suggests that in our model, lung structure changes may be necessary but are not sufficient to impair lung function. SERPINA1A, the mouse ortholog of human α1-antitrypsin, deficiency of which is a known genetic risk factor for emphysema, was down-regulated at the protein level in the in utero SHS-exposed mice. Additionally, DNMT3A protein expression was dysregulated, indicating that DNA methylation occurred in the lungs.

Conclusions: Our results indicate that in utero SHS exposure alone alters both lung function and structure well into adulthood (15 weeks) in male mice. Furthermore, lung function alterations in this model are sex-specific, with males being more susceptible to in utero SHS effects. Overall, our data suggest that in utero SHS exposure alone can predispose to adult lung diseases.
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http://dx.doi.org/10.1186/s12931-017-0591-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5485620PMC
June 2017

In utero exposure to second-hand smoke activates pro-asthmatic and oncogenic miRNAs in adult asthmatic mice.

Environ Mol Mutagen 2016 Apr 9;57(3):190-9. Epub 2016 Feb 9.

Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana.

Exposures to environmental pollutants contribute to dysregulated microRNA (miRNA) expression profiles, which have been implicated in various diseases. Previously, we reported aggravated asthmatic responses in ovalbumin (OVA)-challenged adult mice that had been exposed in utero to second-hand smoke (SHS). Whether in utero SHS exposure dysregulates miRNA expression patterns in the adult asthma model has not been investigated. Pregnant BALB/c mice were exposed (days 6-19 of pregnancy) to SHS (10 mg/m(3)) or HEPA-filtered air. All offspring were sensitized and challenged with OVA (19-23 weeks) before sacrifice. RNA samples extracted from lung homogenates, were subjected to RNA sequencing (RNA-seq). RNA-seq identified nine miRNAs that were most significantly up-regulated by in utero SHS exposure. Among these nine, miR-155-5p, miR-21-3p, and miR-18a-5p were also highly correlated with pro-asthmatic Th2 cytokine levels in bronchoalveolar lavage fluid. Further analysis indicated that these up-regulated miRNAs shared common chromosome locations, particularly Chr 11C, with pro-asthmatic genes. These three miRNAs have also been characterized as oncogenic miRNAs (oncomirs). We cross-referenced miRNA-mRNA expression profiles and identified 16 tumor suppressor genes that were down-regulated in the in utero-exposed offspring and that are predicted targets of the up-regulated oncomirs. In conclusion, in utero SHS exposure activates pro-asthmatic genes and miRNAs, which colocalize at specific chromosome locations, in OVA-challenged adult mice. The oncogenic characteristics of the miRNAs and putative miRNA-mRNA regulatory networks suggest that the synergistic effect of in utero SHS exposure and certain adult irritants may promote an oncogenic milieu in mouse lungs via inhibition of miRNA-regulated tumor suppressor genes.
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http://dx.doi.org/10.1002/em.21998DOI Listing
April 2016

In utero exposure to second-hand smoke aggravates the response to ovalbumin in adult mice.

Am J Respir Cell Mol Biol 2013 Dec;49(6):1102-9

1 Department of Comparative Biomedical Sciences, and.

Second-hand smoke (SHS) exposure in utero exacerbates adult responses to environmental irritants. We tested the hypothesis that effects of in utero SHS exposure on modulating physiological and transcriptome responses in BALB/c mouse lungs after ovalbumin (OVA) challenge extend well into adulthood, and that the responses show a sex bias. We exposed BALB/c mice in utero to SHS or filtered air (AIR), then sensitized and challenged all offspring with OVA from 19 to 23 weeks of age. At the end of the adult OVA challenge, we evaluated pulmonary function, examined histopathology, analyzed bronchoalveolar lavage fluid (BALF), and assessed gene expression changes in the lung samples. All groups exhibited lung inflammation and inflammatory cell infiltration. Pulmonary function testing (airway hyperresponsiveness [AHR], breathing frequency [f]) and BALF (cell differentials, Th1/Th2 cytokines) assessments showed significantly more pronounced lung responses in the SHS-OVA groups than in AIR-OVA groups (AHR, f; eosinophils, neutrophils; IFN-γ, IL-1b, IL-4, IL-5, IL-10, IL-13, KC/CXCL1, TNF-α), with the majority of responses being more pronounced in males than in females. SHS exposure in utero also significantly altered lung gene expression profiles, primarily of genes associated with inflammatory responses and respiratory diseases, including lung cancer and lung fibrosis. Altered expression profiles of chemokines (Cxcl2, Cxcl5, Ccl8, Ccl24), cytokines (Il1b, Il6, Il13) and acute phase response genes (Saa1, Saa3) were confirmed by qRT-PCR. In conclusion, in utero exposure to SHS exacerbates adult lung responses to OVA challenge and promotes a pro-asthmatic milieu in adult lungs; further, males are generally more affected by SHS-OVA than are females.
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http://dx.doi.org/10.1165/rcmb.2013-0164OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3931120PMC
December 2013

In utero exposure to second-hand smoke aggravates adult responses to irritants: adult second-hand smoke.

Am J Respir Cell Mol Biol 2012 Dec 6;47(6):843-51. Epub 2012 Sep 6.

Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA.

In utero exposure to second-hand smoke (SHS) is associated with exacerbated asthmatic responses in children. We tested the hypothesis that in utero SHS will aggravate the lung responses of young adult mice re-exposed to SHS. We exposed Balb/c mice in utero to SHS (S) or filtered air (AIR; A), and re-exposed the male offspring daily from 11-15 weeks of age to either SHS (AS and SS) or AIR (AA and SA). After the adult exposures, we analyzed samples of bronchoalveolar lavage fluid (BALF), examined the results of histopathology, and assessed pulmonary function and gene expression changes in lung samples. In SS mice, compared with the other three groups (AA, AS, and SA), we found decreases in breathing frequency and increases in airway hyperresponsiveness (AHR), as well as low but significantly elevated concentrations of BALF proinflammatory cytokines (IL-1b, IL-6, and keratinocyte-derived chemokine). Lung morphometric analyses revealed enlarged airspaces and arteries in SA and SS mice compared with their in utero AIR counterparts, as well as increased collagen deposition in AS and SS mice. Unique gene expression profiles were found for in utero, adult, and combined exposures, as well as for mice with elevated AHR responses. The profibrotic metalloprotease genes, Adamts9 and Mmp3, were up-regulated in the SS and AHR groups, suggesting a role for in utero SHS exposure on the adult development of chronic obstructive pulmonary disease. Our results indicate that in utero exposures to environmentally relevant concentrations of SHS alter lung structure more severely than do adult SHS exposures of longer duration. These in utero exposures also aggravate AHR and promote a profibrotic milieu in adult lungs.
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http://dx.doi.org/10.1165/rcmb.2012-0241OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3547098PMC
December 2012

Zebrafish embryos sequester and retain petrochemical combustion products: developmental and transcriptome consequences.

Aquat Toxicol 2012 Feb 6;108:23-32. Epub 2011 Oct 6.

Department of Comparative Biomedical Sciences, Louisiana State University, School of Veterinary Medicine, Baton Rouge, LA 70803, USA.

Zebrafish embryos are a model for studying effects of environmental stressors on development. Incomplete combustion of the environmentally relevant volatile petrochemical, 1,3-butadiene (BD) yields butadiene soot (BDS) nanoparticles, to which polynuclear aromatic hydrocarbons (PAHs) are adsorbed. In mammalian cells these PAHs are concentrated in lipid droplets and trigger up-regulation of biotransformation, oxidative stress and inflammatory genes. The present study was designed to determine whether: (a) PAH-rich BDS elicits alterations in zebrafish embryo development; (b) BDS-exposed zebrafish embryos sequester PAHs in select tissues; and (c) developmental abnormalities are correlated with altered gene expression patterns. 1-day old zebrafish embryos were exposed for 48 h to BDS (0, 6, 30 or 60 μg/ml) sprinkled on the water surface. PAH localization was tracked by fluorescence. Developmental responses (pericardial edema, yolk sac swelling, axial malformations) were monitored by microscopy. Gene expression changes were assessed by gene microarray and qRT-PCR. Our results show that PAHs localized with endogenous lipids in the yolk sac and in hatching gland cells. PAHs were retained at least 8 days after exposures ended. Dose-dependent pericardial and yolk sac edema and axial malformations were prominent and accompanied by up-regulation of biotransformation and oxidative stress gene cascades. Thus, zebrafish embryos should be useful for predicting the potential for developmental toxicity following exposure to PAH-rich petrochemical soots, e.g., those arising from attempts at oil spill remediation by combustion.
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http://dx.doi.org/10.1016/j.aquatox.2011.09.025DOI Listing
February 2012

Isolation and characterization of a novel thraustochytrid-like microorganism that efficiently produces docosahexaenoic acid.

Biotechnol Lett 2006 Feb;28(3):197-202

Laboratory of Environmental Molecular Biology, Graduate School of Environmental Earth Science, Hokkaido University, Sapporo, Kita-ku, 060-0810, Japan.

A thraustochytrid-like microorganism (strain 12B) was isolated from the mangrove area of Okinawa, Japan. On the basis of its ectoplasmic net structure and biflagellate zoospores we determined strain 12B to be a novel member of the phylum Labyrinthulomycota in the kingdom Protoctista. When grown on glucose/seawater at 28 degrees C, it had a lipid content of 58% with docosahexaenoic acid (DHA; 22:6 n-3) at 43% of the total fatty acids. It had a growth rate of 0.38 h(-1). The DHA production rate of 2.8 +/- 0.7 g l(-1) day(-1) is the highest value reported for any microorganism.
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http://dx.doi.org/10.1007/s10529-005-5335-4DOI Listing
February 2006