Protective Effects of Hydrogen-Rich Saline Against Lipopolysaccharide-Induced Alveolar Epithelial-to-Mesenchymal Transition and Pulmonary Fibrosis

Abstract

Background: Fibrotic change is one of the important reasons for the poor prognosis of patients with acute respiratory distress syndrome (ARDS). The present study investigated the effects of hydrogen-rich saline, a selective hydroxyl radical scavenger, on lipopolysaccharide (LPS)-induced pulmonary fibrosis. Material/Methods: Male ICR mice were divided randomly into 5 groups: Control, LPS-treated plus vehicle treatment, and LPS-treated plus hydrogen-rich saline (2.5, 5, or 10 ml/kg) treatment. Twenty-eight days later, fibrosis was assessed by determination of collagen deposition, hydroxyproline, and type I collagen levels. Development of epithelial-to-mesenchymal transition (EMT) was identified by examining protein expressions of E-cadherin and a-smooth muscle actin (a-SMA). Transforming growth factor (TGF)-b1 content, total antioxidant capacity (T-AOC), malondialdehyde (MDA) content, catalase (CAT), and superoxide dismutase (SOD) activity were determined. Results: Mice exhibited increases in collagen deposition, hydroxyproline, type I collagen contents, and TGF-b1 production in lung tissues after LPS treatment. LPS-induced lung fibrosis was associated with increased expression of a-SMA, as well as decreased expression of E-cadherin. In addition, LPS treatment increased MDA levels but decreased T-AOC, CAT, and SOD activities in lung tissues, indicating that LPS induced pulmonary oxidative stress. Hydrogen-rich saline treatment at doses of 2.5, 5, or 10 ml/kg significantly attenuated LPS-induced pulmonary fibrosis. LPS-induced loss of E-cadherin in lung tissues was largely reversed, whereas the acquisition of a-SMA was dramatically decreased by hydrogen-rich saline treatment. In addition, hydrogen-rich saline treatment significantly attenuated LPS-induced oxidative stress. Conclusions: Hydrogen-rich saline may protect against LPS-induced EMT and pulmonary fibrosis through suppressing oxidative stress.

Study details

Article type

Original Research

Disease / injury model

LPS-induced pulmonary fibrosis (ARDS model)

Duration

28 days

Dose comparison

Three different doses of hydrogen-rich saline (2.5, 5, and 10 ml/kg) were compared for their effects on LPS-induced pulmonary fibrosis.

Dose-dependent effect

Yes

Outcome

Positive

Findings

Hydrogen-rich saline significantly attenuated LPS-induced pulmonary fibrosis and epithelial-to-mesenchymal transition (EMT) in mice, likely through suppression of oxidative stress and TGF-β1 production.