Ozone-Induced Injury and Oxidative Stress in Bronchiolar Epithelium Are Associated with Altered Pulmonary Mechanics

Abstract

In these studies, we analyzed the effects of ozone on bronchiolar epithelium. Exposure of rats to ozone (2 ppm, 3 h) resulted in rapid (within 3 h) and persistent (up to 72 h) histological changes in the bronchiolar epithelium, including hypercellularity, loss of cilia, and necrotizing bronchiolitis. Perivascular edema and vascular congestion were also evident, along with a decrease in Clara cell secretory protein in bronchoalveolar lavage, which was maximal 24 h post-exposure. Ozone also induced the appearance of 8-hydroxy-2'-deoxyguanosine, Ym1, and heme oxygenase-1 in the bronchiolar epithelium. This was associated with increased expression of cleaved caspase-9 and beclin-1, indicating initiation of apoptosis and autophagy. A rapid and persistent increase in galectin-3, a regulator of epithelial cell apoptosis, was also observed. Following ozone exposure (3-24 h), increased expression of cyclooxygenase-2, inducible nitric oxide synthase, and arginase-1 was noted in bronchiolar epithelium. Ozone-induced injury and oxidative stress in bronchiolar epithelium were linked to methacholine-induced alterations in pulmonary mechanics. Thus, significant increases in lung resistance and elastance, along with decreases in lung compliance and end tidal volume, were observed at higher doses of methacholine. This indicates that ozone causes an increase in effective stiffness of the lung as a consequence of changes in the conducting airways. Collectively, these studies demonstrate that bronchiolar epithelium is highly susceptible to injury and oxidative stress induced by acute exposure to ozone; moreover, this is accompanied by altered lung functioning.

Limonene and its ozone-initiated reaction products attenuate allergic lung inflammation in mice

“…In several cell and tissue models, HO-1 is upregulated in response to cellular stress (Ryter et al 2006), including exposures to environmental pollutants such as ozone (Sunil et al 2013;Valacchi et al 2004), or when cytoprotective responses are required (Ryter et al 2006). Therefore, HO-1 was selected to investigate whether antioxidant effects of limonene (and the reaction mixture) could be detected.…”

“…However, HO-1 was not differentially expressed between the four airborne exposures. The regulation of HO-1 is biphasic and as a response to oxidative stress, HO-1 is upregulated within 6 h (Risom et al 2003;Sunil et al 2013). At later time points (including in the lung), HO-1 is involved in suppressing inflammation and initiating wound healing (Lee et al 2009;Ryter et al 2006), which may be the reason for a comparable upregulation in the groups of allergic mice.…”

Towards molecular mechanisms regulating the expression of galectins in cancer cells under microenvironmental stress conditions

“…In a different context, interaction between galectin-3 and IL-10 was required to protect human breast carcinoma BT549 cells against liver ischemia-reperfusion-induced cytotoxicity [106]. Oxidative stress induced by ozone exposure was also associated with the rapid (within 3 h) and prolonged (up to 72 h) accumulation of galectin-3 in the bronchiolar epithelium and alveolar macrophages of rats [107,108]. Since galectin-3 has been found to have a positive effect on the re-epithelialization of wounds [109], it is anticipated that this effect may be involved in both the protection against the oxidative damage of lungs and wound repair [107].…”

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“…Similarly, heat waves lead to inactive lifestyles or physical inactivity, obesity risk factors for NCDs. Importantly, climate change is directly associated with cancer via acute O3 exposure-induced oxidative stress, inflammation, DNA damage, induction of "survival mutations "in the proto-oncogenes (Ras & c-MYC) and tumour suppressor genes (p53 & RB), metabolic reprogramming and induction of the seven cancer hallmarks [25,31,32,33] .…”

“…This leads to a vicious cycle of chronic inflammation, immune activation, oxidative stress, metabolic reprogramming, induction of the seven cancer hall marks, strongly linked with initiation, maintenance and progression of cancer. According to Colottaet al (2009) [31] , Candido&Hagemann (2013) [32] , Ataie-Kachoie et al (2014) [33] , cancer is described as a failed resolution of the inflammatory process or tissue remodeling, which develops in a setting of chronic oxidative stress, inflammation and immune activation. Directly, increased exposure to ultraviolet B (UVB) radiation resulting from depletion of stratospheric O3 has been reported to cause basal and squamous cell skin cancer.…”