Protective effects of methane-rich saline on mice with allergic asthma by inhibiting inflammatory response, oxidative stress and apoptosis

Abstract

Background: Asthma is a common cause of breathing difficulty in children and adults, and is characterized by chronic airway inflammation that is poorly controlled by available treatments. This results in severe disability and applies a huge burden to the public health system. Methane has been demonstrated to function as a therapeutic agent in many diseases. The aim of the present study was to explore the effect of methane-rich saline (MRS) on the pathophysiology of a mouse model of asthma and its underlying mechanism. Methods: A murine model of ovalbumin (OVA)-induced allergic asthma was applied in this study. Mice were divided into three groups: a control group, an OVA group, and OVA-induced asthmatic mice treated with MRS as the third group. Lung resistance index (RI) and dynamic compliance (Cdyn) were measured to determine airway hyper-responsiveness (AHR). Haematoxylin and eosin (H&E) staining was performed and scored to show histopathological changes. Cell counts of bronchoalveolar lavage fluid (BALF) were recorded. Cytokines interleukin (IL)-4, IL-5, IL-13, tumor necrosis factor α (TNF-α), and C-X-C motif chemokine ligand 15 (CXCL15) from BALF and serum were measured by enzyme-linked immunosorbent assay (ELISA). The oxidative stress indexes, including malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), myeloperoxidase (MPO), and 8-hydroxydeoxyguanosine (8-OHdG), were determined using commercial kits. Apoptosis was evaluated by western blot, quantitative real-time polymerase chain reaction (qRT-PCR), and biochemical examination. Results: MRS administration reversed the OVA-induced AHR, attenuated the pathological inflammatory infiltration, and decreased the cytokines IL-4, IL-5, IL-13, TNF-α, and CXCL15 in serum and BALF. Moreover, following MRS administration, the oxidative stress was alleviated as indicated by decreased MDA, MPO, and 8-OHdG, and elevated SOD and GSH. In addition, MRS exhibited an anti-apoptotic effect in this model, protecting epithelial cells from damage. Conclusions: Methane improves pulmonary function and decreases infiltrative inflammatory cells in the allergic asthmatic mouse model. This may be associated with its anti-inflammatory, antioxidative, and anti-apoptotic properties.

The Hydroalcoholic Extract of Nasturtium officinale Reduces Lung Inflammation and Oxidative Stress in an Ovalbumin-Induced Rat Model of Asthma

“…Asthma is a chronic respiratory disease with various clinical and pathophysiological profiles including increased mucus secretion, narrowing of the airways, reversible bronchial obstruction, goblet cell hyperplasia, airway hyper responsiveness (AHR), as well as identified acute and chronic inflammation [ 1 , 2 ]. In addition to the aforementioned disease characteristics, asthma has recently been defined as a heterogeneous disease or complex syndrome and can be classified into several phenotypes and endotypes, each with specific clinical and pathological attributes [ 3 , 4 ].…”

“…Inflammation of the airways is associated with the reaction of various immune cells and different mediators [ 11 ]. They secrete several immune cells, including T helper 2 cells (Th2), mast cells, eosinophils, airway epithelial cells, cytokines, chemokines, and inflammatory mediators that damage lung tissue [ 2 ]. Th2 lymphocytes produce cytokines such as interleukins-4, 5, and 13 (IL-4, IL-5, IL-13, respectively), leading to the production of immunoglobulin E , mucosal metaplasia, and increased production of eotaxins and eosinophils in the airways [ 9 ].…”

Methane-Rich Saline Counteracts Cholestasis-Induced Liver Damage via Regulating the TLR4/NF-κB/NLRP3 Inflammasome Pathway

“…Methane possesses antioxidative, anti-inflammatory, and antiapoptotic properties, which have been proved through a septic mouse model [13]. Furthermore, methane exhibited good effects on sepsis-induced mice kidney injury, intestinal IR injury, and liver IRI [8, 12].…”

“…The methane saline was produced as previously described which was freshly prepared 1 day before experiments to ensure a steady concentration [12]. The concentration of MRS was 1.2-1.5 mmol/L which was detected by using gas chromatography as the previous study [13].…”

Bioactivity of Inhaled Methane and Interactions With Other Biological Gases

“…The myocardial OxPhos capacity was more preserved and cytochrome c release was decreased as a result of CH 4 -enriched storage, with the relative mRNA expression for hypoxia-and ER stress-associated genes (including HIF-1α) also being significantly reduced (Benke et al, 2021). Indeed, several previous studies demonstrated that exogenous CH 4 modulates the intrinsic, mitochondrial pathway of pro-apoptotic activation in model experiments (Ye et al, 2015;Chen et al, 2016;Liu et al, 2016;Jia et al, 2018) and CH 4 administration exhibited anti-apoptotic effects and protected the pulmonary epithelial cells in a murine model of ovalbumin-induced allergic asthma as well (Zhang et al, 2019). More importantly, the anti-apoptotic properties of CH 4 inhalation were associated with improved pulmonary compliance and surfactant production in a rodent model of lung IR injury (Zhang et al, 2021).…”