Hyperbaric Oxygen Ameliorates Bleomycin-Induced Pulmonary Fibrosis in Mice

Abstract

The prevalence of pulmonary fibrosis is increasing with an aging population and its burden is likely to increase following COVID-19, with large financial and medical implications. As approved therapies in pulmonary fibrosis only slow disease progression, there is a significant unmet medical need. Hyperbaric oxygen (HBO) is the inhaling of pure oxygen, under the pressure of greater than one atmosphere absolute, and it has been reported to improve pulmonary function in patients with pulmonary fibrosis. Our recent study suggested that repetitive HBO exposure may affect biological processes in mice lungs such as response to wounding and extracellular matrix. To extend these findings, a bleomycin-induced pulmonary fibrosis mouse model was used to evaluate the effect of repetitive HBO exposure on pulmonary fibrosis. Building on our previous findings, we provide evidence that HBO exposure attenuates bleomycin-induced pulmonary fibrosis in mice. In vitro, HBO exposure could reverse, at least partially, transforming growth factor (TGF)-β–induced fibroblast activation, and this effect may be mediated by downregulating TGF-β–induced expression of hypoxia inducible factor (HIF)-1α. These findings support HBO as a potentially life-changing therapy for patients with pulmonary fibrosis, although further research is needed to fully evaluate this.

Integrated analysis reveals the protective mechanism and therapeutic potential of hyperbaric oxygen against pulmonary fibrosis

“…HBO alleviates hypoxia in multiple conditions, including the hypoxemia caused by COVID-19 infection, 49 solid tumors, 50 , 51 , 52 and focal cerebral ischemia model. 53 In our previous study, we provided evidence that HBO treatment reduces HIF-1α levels in lung fibroblast induced by TGF-β, 5 supports the role of HBO in reversing hypoxia. It was reported that HBO ameliorates the EMT phenomenon in keloid tissue, 54 induces mesenchymal-to-epithelial transition in a dimethyl-alpha-benzantracene mammary rat adenocarcinoma model revealed by gene expression profiling, 55 and represses EMT and Warburg effect in hypoxic non-small cell lung cancer cells.…”

“…4 A, B). 5 To determine the underlying molecular mechanism, we characterized the global transcriptomic changes in bleomycin-challenged mice lungs exposed to HBO by performing RNA-Seq. Genes with a P value less than 0.05 and fold change above 1.5 were considered as DEGs.…”

“…The bleomycin-induced pulmonary fibrosis mouse model was constructed and treated with HBO as previously reported. 5 The hematoxylin and eosin (H/E) staining was performed to confirm the presence of pulmonary fibrosis. The details of these experiments can be found in the Supplementary methods.…”

“…Previously we reported that hyperbaric oxygen (HBO) treatment attenuates a single dose of intratracheal administrated bleomycin-induced pulmonary fibrosis in mice, 5 however, the underlying molecular mechanism is to be clarified. HBO treatment is to inhale pure oxygen under a pressure of more than 1 atmosphere absolute (ATA).…”

The Mechanisms of Action of Hyperbaric Oxygen in Restoring Host Homeostasis during Sepsis

“…Conversely, when HBO 2 treatment is administered in hypoxic conditions with a derivational elevated HIF-1α, HBO 2 treatment decreased the disease-mediated high levels of HIF-1α [ 61 , 119 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 ]. The evaluation of studies performed in conditions of relative hypoxia secondary to inflammation indicates that the effect of HBO 2 on HIF-1α protein expression is dependent on the number of HBO 2 sessions administered, with HBO 2 having an increasing effect when administered in up to five sessions [ 140 , 141 , 142 , 143 ], and treatment with more than six sessions having a decreasing effect under these conditions [ 47 , 120 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 , 152 , 153 , 154 , 155 , 156 ]. However, six study results were not supportive of this trend [ 117 , 140 , 141 , 157 , 158 , 159 ].…”