Hydrogen-containing saline alleviates pressure overload-induced interstitial fibrosis and cardiac dysfunction in rats

Abstract

Cardiac fibrosis induced by sustained pressure overload contributes to heart failure. Oxidative stress serves an important role in cardiac remodeling and heart failure independent of etiological factors. The application of hydrogen as an antioxidant is a novel concept in disease treatment, however no studies as present have investigated the effects of hydrogen on cardiac fibrosis. In the present study, the effects of hydrogen on pressure overload‑induced cardiac fibrosis and heart failure were investigated in abdominal aortic‑constricted rats. Masson's trichrome staining and echocardiography were used to evaluate the fibrotic area and cardiac function, respectively. Reactive oxygen species (ROS) content was detected by immunofluorescence. Malondialdehyde (MDA) concentration, the activity of superoxide dismutase (SOD) and hydroxyproline content were measured by spectrophotometry. Western blot analysis was used to detect the protein levels of transforming growth factor (TGF)‑β1, connective tissue growth factor (CTGF), NADPH oxidases (NOX)2, NOX4, p38 mitogen‑activated protein kinase (MAPK) and Smad2/3. Reverse transcription‑quantitative polymerase chain reaction was performed to detect the mRNA expression of collagen I (Col I) and fibronectin 1 (FN1). Hydrogen‑containing saline (HCS) treatment was observed to improve interstitial fibrosis and cardiac function and to decrease the level of ROS, the oxidative‑stress marker MDA and expression of NOXs, while increasing the activity of the anti‑oxidant enzyme SOD. HCS treatment also decreased the phosphorylation of p38 MAPK and Smad2/3, and the expression of TGF‑β1 and CTGF, which were accompanied by reduced hydroxyproline content, Col I and FN1 mRNA levels. These results indicate that HCS treatment can improve cardiac function by reducing interstitial fibrosis in pressure‑overloaded rats through its anti‑oxidative properties and via suppression of TGF‑β1 signaling.

Study details

Article type

Original Research

Disease / injury model

Pressure overload-induced cardiac fibrosis and heart failure (abdominal aortic constriction in rats)

Duration

16 weeks

Dose-dependent effect

No

Outcome

Positive

Findings

Hydrogen-containing saline (HCS) treatment improved cardiac function and reduced interstitial fibrosis in pressure-overloaded rats. HCS decreased ROS, MDA, NOX2/NOX4, TGF-β1, CTGF, p38 MAPK phosphorylation, and increased SOD activity, indicating anti-oxidative and anti-fibrotic effects via suppression of TGF-β1 signaling.