Document Type

Dissertation

Date of Award

8-2021

School/College

College of Science, Engineering, and Technology (COSET)

Degree Name

Ph.D. in Environmental Toxicology

Committee Chairperson

Shishir Shishodia

Committee Co-Chairperson

Jason Rosenzweig

Committee Member 1

Maruthi Sridhar Balaji Bhaskar

Committee Member 2

Daniel Vrinceanu

Committee Member 3

Hyun-Min Hwang

Keywords

Air Pollution, Indoor Dust, Inflammation, Lung cells, MAPK Oxidative Stress.

Abstract

These days, people spend most of their time indoors. Therefore, indoor dust can be one of the main pathways of exposure to toxic contaminants. Indoor dust is a complex mixture of particles with organic and inorganic pollutants, such as heavy metals, smoke residues, flame retardants, pesticides, polycyclic aromatic hydrocarbons, and plasticizers. Depending on the size and the composition, indoor dust has been associated with different toxicological effects because of its ability to modify several biological activities, activate different cellular pathways, and induce DNA adducts. These alterations can lead to respiratory diseases like asthma, chronic obstructive pulmonary disease, lung fibrosis and cancer. This study aimed to determine the effect of the indoor dust (Trace Elements Indoor Dust and Organic Contaminants House Dust) on cell viability, cytotoxicity, cellular death mechanism, cellular oxidative stress, inflammasome activation, and Mitogen-Activated Protein Kinase pathway activation in normal human bronchial epithelial cells (BEAS-2B) after exposure to different dust concentrations (10, 25, 50, 75, 100, 250, and 500 µg/ml). The research covers the proliferation of normal human bronchial epithelial cells using 3-(4,5 dimethyl-2-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Viability and apoptosis were measured in BEAS-2B cells by the Triplex assay. Cytotoxicity was measured using LDH-Glo cytotoxicity assay. Reactive oxygen species (ROS) were measured by the dichlorofluorescein (DCFH) oxidation assay and the ROS-Glo-H2O2 assay. For detection of inflammation, Inflammasome-Glo Caspase-1 assay was used. MAPK protein levels (JNK, ERK1/2, and p38) and antioxidant enzymes’ levels (Superoxide Dismutase-1, Superoxide Dismutase-2, Catalase, and Glutathione Peroxidase) were determined using western blotting. Our findings indicate that indoor dust exposure results in cell growth suppression, cell cytotoxicity, ROS overproduction, antioxidant enzymes activation, activation of the inflammatory response, and MAPK pathway activation in normal lung cells, which together cause apoptotic, necrotic, and pyroptotic cell death, and that may pose a risk for respiratory disorders and airway injury.

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.