Protective Effects of Methane‐Rich Saline on Rats with Lipopolysaccharide‐Induced Acute Lung Injury

Abstract

Objective. The aim of this research is to evaluate the protective effects of methane-rich saline (MS) on lipopolysaccharide- (LPS-) induced acute lung injury (ALI) and investigate its potential antioxidative, anti-inflammatory, and antiapoptotic activities. Methods. LPS-induced (20 mg/kg) ALI rats were injected with MS (2 ml/kg and 20 ml/kg) before the initiation of LPS induction. Survival rate was determined until 96 h after LPS was induced. Lung injury was assayed by oxygenation index, lung permeability index (LPI), wet-to-dry weight (W/D), and histology. The cells in the bronchoalveolar lavage fluid (BALF) were counted. Oxidative stress was examined by the level of malondialdehyde (MDA) and superoxide dismutase (SOD). Inflammatory factors including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in BALF were determined by ELISA. Lung tissue apoptosis was detected by TUNEL staining and western blotting of caspase-3. Results. It was found that methane significantly prolonged the rat survival, decreased the lung W/D ratio and the content of the inflammatory factors, and reduced the amount of caspase-3 and apoptotic index. In addition, MS increased the level of SOD and decreased the level of MDA significantly. Conclusions. MS protects the LPS-challenged ALI via antioxidative, anti-inflammatory, and antiapoptotic effect, which may prove to be a novel therapy for the clinical management of ALI.

Methane Medicine: A Rising Star Gas with Powerful Anti‐Inflammation, Antioxidant, and Antiapoptosis Properties

“…The hallmark of ALI is injury to pulmonary capillary endothelial cells and alveolar epithelial cells and the activation of the innate immune, leading to diffuse edema in pulmonary interstitial and alveolar [ 26 ]. Sun et al showed that methane-rich saline protected the lipopolysaccharide- (LPS-) challenged ALI via antioxidative, anti-inflammatory, and antiapoptotic effects, which had potential to be a new therapy for the treatment of ALI [ 27 ]. According to their results, it showed that the survival period was prolonged significantly after methane-rich saline treatment.…”

Methane-Rich Saline Alleviates CA/CPR Brain Injury by Inhibiting Oxidative Stress, Microglial Activation-Induced Inflammatory Responses, and ER Stress-Mediated Apoptosis

“…An emerging star gas, methane, as the richest organic gas in nature, is colorless, odorless, and nontoxic and possesses reducibility, which has attracted increasing attention in recent years, especially for the treatment of diseases [ 15 ]. Studies indicate that methane plays a unique biological role in anti-inflammatory, antioxidation, antiapoptosis, and other cell protection, which has been confirmed in many different animal experiments [ 16 – 18 ]. Methane has been shown to exhibit protective effects in hepatic, myocardial, and renal ischemia-reperfusion injury through antioxidative, anti-inflammatory, and antiapoptotic effects [ 19 – 21 ].…”

Mitochondria As Sources and Targets of Methane

“…The anti-apoptotic effect is one of the most studied properties of CH 4 . Several studies demonstrated that CH 4 modulates the intrinsic pathway of apoptosis ( 9 – 11 , 29 , 30 , 55 – 58 ). The intrinsic pathway of apoptosis, also called the mitochondrial pathway owing to the essential involvement of mitochondria ( 59 ), which are not only the site where anti- and pro-apoptotic proteins interact but also the origins of high range of signal pathways that initiate the activation of caspases through various mechanisms ( 60 ).…”

“…Likewise, in an experimental spinal cord IR scenario, CH 4 was proven to significantly reduce the number of apoptotic cells (confirmed by TUNEL staining) and also the amount of cleaved caspase-3 and caspase-9 proteins and to attenuate cytosolic Cyt c release ( 29 ). In addition, CH 4 -rich fluids significantly reduced the expression of cleaved caspase-3 and also decreased the apoptotic cell number in rodents exposed to LPS-induced acute lung injury ( 58 ). In a hepatic IR model, CH 4 inhalation could effectively attenuate the apoptosis-linked morphological changes in the liver and the TUNEL positivity of hepatocytes ( 11 ).…”