Hydrogen inhalation attenuated bleomycin‐induced pulmonary fibrosis by inhibiting transforming growth factor‐β1 and relevant oxidative stress and epithelial‐to‐mesenchymal transition

Abstract

New Findings What is the central question of this study?The aim was to explore the effects and underlying mechanisms of H2 on bleomycin‐induced pulmonary fibrosis. What are the main findings and its importance?Our results indicate that, in bleomycin‐induced pulmonary fibrosis, H2 inhalation attenuated oxidative stress and reversed the pulmonary epithelial‐to‐mesenchymal transition process by reducing reactive oxygen species production and inhibiting the expression of transforming growth factor‐β1, α‐smooth muscle actin and collagen I to improve fibrotic injury and exert anti‐fibrogenic effects. Thus, H2 inhalation has promising therapeutic potential as a useful adjuvant treatment for patients with idiopathic pulmonary fibrosis, which deserves further study and evaluation. Abstract Hydrogen (H2) can protect against tissue damage. The effect of H2 inhalation therapy on the pathogenesis of pulmonary fibrosis remains unknown. This study was designed to explore the effects and underlying mechanisms of H2 inhalation on bleomycin (BLM)‐induced pulmonary fibrosis. A rat model of pulmonary fibrosis was established with BLM. Rats were randomly divided into control and H2 inhalation groups. Haematoxylin and Eosin staining and Mason's Trichrome staining were performed to evaluate pulmonary fibrosis injury, inflammatory cell infiltration, structural disorder and collagen deposition. qRT‐PCR and western blot assays were used to determine the expression of TNF‐α, TGF‐β1, α‐SMA, E‐cadherin, N‐cadherin, vimentin, VEGF and collagen type I at both mRNA and protein levels. The contents of reactive oxygen species, TGF‐β1, TNF‐α, malondialdehyde and hydroxyproline were determined with biochemical test kits or ELISA kits. Bleomycin‐stimulated rats exhibited typical symptoms of pulmonary fibrosis, which featured an increase in collagen deposition, alveolitis, fibrosis and parenchymal structural disorder in the lung. However, BLM‐induced oxidative stress was attenuated by H2 inhalation therapy, which reduced the contents of reactive oxygen species, malondialdehyde and hydroxyproline, enhanced the activity of glutathione peroxidase and decreased the expression of TGF‐β1 and TNF‐α. In addition, H2 inhalation also inhibited BLM‐induced epithelial‐to‐mesenchymal transition by inhibiting TGF‐β1, increasing the expression level of the epithelial cell marker E‐cadherin, and decreasing the expression level of the mesenchymal cell marker vimentin in a time‐dependent manner. In addition, H2 inhalation downregulated α‐SMA expression and suppressed collagen I generation, exerting anti‐fibrogenic effects. Hydrogen inhalation therapy attenuates BLM‐induced pulmonary fibrosis by inhibiting TGF‐β1, relevant oxidative stress and epithelial‐to‐mesenchymal transition.

Molecular hydrogen regulates PTEN‐AKT‐mTOR signaling via ROS to alleviate peritoneal dialysis‐related peritoneal fibrosis

“…It is believed that it has biological effects such as anti‐oxidation, anti‐inflammation, and anti‐apoptosis, and has extremely high biosafety. Hydrogen has already been reported to protect kidney, liver, heart, and lung from fibrosis . Studies have also suggested that peritoneal dialysate containing hydrogen could preserve MCs, indicating hydrogen may suppress peritoneal fibrosis .…”

“…Hydrogen has already been reported to protect kidney, liver, heart, and lung from fibrosis. [16][17][18][19] Studies have also suggested that peritoneal dialysate containing hydrogen could preserve MCs, indicating hydrogen may suppress peritoneal fibrosis. 20 A clinical case report has indicated that hydrogen-dissolved peritoneal dialysate could successfully treat a patient with encapsulating peritoneal sclerosis.…”

The Effects of Inhaling Hydrogen Gas on Macrophage Differentiation, Fibrosis and Lung Function in Mice with Bleomycin-induced Lung Injury

“…A previous study using a bleomycin-induced ALI model was reported by Gao and colleagues who found that hydrogen attenuated oxidative stress, increased the expression of the antioxidant glutathione peroxidase, and consequently suppressed the expression of reactive oxygen species in the injured lung [13]. The expression of TGF-β1 was also suppressed and epithelial-to-mesenchymal transition was inhibited, which may be one mechanisms involved in brosis suppression by hydrogen treatment.…”

“…Inhalation of hydrogen gas may be a straightforward and promising therapeutic option, because inhaled gaseous molecules can directly reach the alveoli. Additionally, inhaled hydrogen has a low chemical toxicity [11][12][13]. Thus, this gaseous therapy has good clinical feasibility, as long as its ammability can be controlled.…”

Assessment of chromosome stability in boars

“…Bleomycin intercalates into DNA, causing single-and double-strand breaks, thereby arresting cell division and DNA synthesis. Its properties have been exploited to treat some cancers [38][39][40]. Luna et al [41] used the BLM assay to identify chromosomal damage in fertile and sub-fertile female cows.…”