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Toxicity and Toxins
Published in Gary S. Moore, Kathleen A. Bell, Living with the Earth, 2018
Gary S. Moore, Kathleen A. Bell
The respiratory system is composed of the nose, pharynx, larynx, trachea, bronchi, and lungs (Figure 5.2). Its function is to supply oxygen to the body’s cells and to expel carbon dioxide from the body in a process called respiration. The act of breathing or ventilation brings air into and out of the lungs. The exchange of oxygen and carbon dioxide between the atmosphere and blood is known as external respiration, while the exchange of gases between blood and individual cells is called internal respiration. Air is drawn into the nasopharyngeal area through nasal hairs at the vestibule and then over mucous- membrane-covered bony plates called the nasal conchae. These structures combine to filter, warm, and moisten inhaled air. Additionally, nerve endings in this nasal area may be stimulated to cause a sneeze reflex helping to eliminate the mucous and the trapped particles. The inhaled air then enters the trachea-bronchial area where the bronchi branch into numerous bronchioles with even smaller diameters until they terminate into thin-walled, delicate alveoli where gas exchange takes place. The trachea, bronchi, and bronchioles are lined by a velvety layer of cilia with mucous cells throughout. Particles such as dust and pollen of 10 mm or larger are removed by the constant streaming of mucous propelled from the bronchial and tracheal passages by the cilia beating at over 1300 times per minute in a process known as mucociliary streaming. The tube-like structures of the bronchi and trachea are surrounded by layers of smooth muscle that contract in response to irritating substances and allergens (Figure 5.3). This bronchoconstriction narrows the lumen and restricts the flow of air, other gases, and particles from reaching more delicate tissues deeper in the lung. This process may also be combined with excess mucous secretions or other fluids that make breathing difficult. When prolonged and severe, this process can be life threatening as in asthmatic attacks. A cough reflex may be initiated at the level of the bronchi to eliminate accumulated mucous in which foreign substances have become lodged.3,4,6
Assessing the in vitro toxicity of airborne (nano)particles to the human respiratory system: from basic to advanced models
Published in Journal of Toxicology and Environmental Health, Part B, 2023
Maria João Bessa, Fátima Brandão, Fernanda Rosário, Luciana Moreira, Ana Teresa Reis, Vanessa Valdiglesias, Blanca Laffon, Sónia Fraga, João Paulo Teixeira
The defense mechanisms of the airways and lung comprise the cough reflex, the epithelial barrier and lining fluid, the mucociliary escalator, metabolic signaling cascades (e.g., activation of cytochrome P450 family and and/or activation of nuclear factor erythroid 2–related factor 2 (Nrf2)-mediated transcription factors), humoral factors including antimicrobial and surfactant peptides or complement proteins and cells that elicit immune responses, namely epithelial cells, macrophages, monocytes, dendritic cells, neutrophils, natural killer cells, and mast cells (Hastedt et al. 2016; Rothen-Rutishauser et al. 2008). In the large airways, the epithelial lining fluid is composed of a superficial mucus layer overlying a periciliary liquid layer that is responsible for mucociliary clearance through physical unidirectional cilia movement and removal of deposited particles and gases dissolved in the mucus from the respiratory tract (Schuster et al. 2013). Further, the alveolar surface is covered by pulmonary surfactant that also plays a critical role in the clearance of inhaled toxicants including aerosolized (nano)particles (Wohlleben et al. 2016).
Carob extract attenuates brain and lung injury in rats exposed to waterpipe smoke
Published in Egyptian Journal of Basic and Applied Sciences, 2018
Mona Abdel-Rahman, Amira A. Bauomy, Fatma Elzahraa H. Salem, Mona Ahmed Khalifa
The waterpipe smokers had increased cough and biologic abnormalities in several anatomic components in the lung compared to nonsmokers [35]. The cough reflex can be initiated by a wide variety of stimuli [36]. The vagal fibers for cough enter the brainstem (cough center) and relay in the nucleus of the solitary tract with connections to second-order neurons [37,38] . Afferent impulses travel to the dorsal medulla where the reflex is subject to cortical control where cerebral cortex has a role in influencing cough. The brain then sends signals back to the lungs and respiratory muscles [39,40] . Neurotransmitters which involved in the central cough complex are tachykinins, glutamate, g-aminobutyric acid, N-methyl-D-aspartate, 5-HT and DA [37,38,41] . Increased release of substance P is involved in the development of cough and inflammation of the airway, and its production is regulated by dopaminergic neurons in the brainstem.
Effects of fuel components and combustion particle physicochemical properties on toxicological responses of lung cells
Published in Journal of Environmental Science and Health, Part A, 2018
Isabel C. Jaramillo, Anne Sturrock, Hossein Ghiassi, Diana J. Woller, Cassandra E. Deering-Rice, JoAnn S. Lighty, Robert Paine, Christopher Reilly, Kerry E. Kelly
Studying the potential health effects of cdPM derived from commercial engines using commercial fuels, regardless of origin, is often complicated by variations in combustion conditions, exhaust system conditioning, lubricants, and variations in the composition of the commercial fuels. For example, differences in engine operating conditions, fuel, and exhaust system conditioning can all substantially modify the effects of cdPM on cardiac and inflammatory responses in animal models and human subjects.[30–34] These factors likely contribute to the contradictory results reported in the literature regarding the effects of diesel and biodiesel cdPM in biological systems. In fact, McDonald et al.[30] concluded that PM mass concentration alone is an inadequate metric for comparing results among diesel exhaust studies conducted under different conditions of engine type and operation. Our study focused on one variable, difference in fuel, and it is intended to complement engine studies that compare bio-derived and petroleum-based fuels. It utilized particles and particle extracts generated from controlled combustion of two simple biofuel/diesel surrogates (methyl decanoate and dodecane, biofuel-blended diesel (BD), and butanol and dodecane, alcohol-blended diesel (AD)), to address toxicological effects related to environmental cdPM variability. These cdPM and extracts were also compared to a widely studied reference petro-diesel particle (NIST SRM2975; RD). Additionally, this study focused on the role of specific cdPM physicochemical properties, on the activation of a set of toxicologically relevant endpoints using human H441 and THP1 cells as models. The following biological outcomes were evaluated: cytochrome P450 (CYP) 1A1 and 1B1 mRNA induction, enzymes that both detoxify and bioactivate polycyclic aromatic hydrocarbons (PAHs) in human airway epithelial cells[35–37]; secretion of interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNFα, proteins that regulate host-defenses and inflammation) [35,38,39]; activation of transient receptor potential ankyrin-1 (TRPA1), a protein that triggers irritation sensations and the cough reflex via C-fibers, as well as inflammation and edema[40,41]; and oxidizing potential (oxidative stress induced by cdPM is believed to be a cause of many adverse biological effects). Finally, the role of specific cdPM physicochemical properties and their effects on different biological processes were evaluated using a combination of standardized PAH samples and inhibitors of both TRPA1 and oxidative stress.