In vivo study of the effects of exogenous hydrogen sulfide on lung mitochondria in acute lung injury in rats

Abstract

BackgroundAcute lung injury (ALI) is a serious disease with high incidence in ICU, and impaired mitochondria function plays a significant role in ALI. In this study, we examined the possible roles of exogenous hydrogen sulfide (H2S) in lung mitochondria regulation in ALI rats.MethodsThe rat ALI model was induced by an intra-tongue vein Lipopolysaccharide (LPS) injection. We used sodium hydrosulphide (NaHS) as the H2S donor. We randomly divided 40 Sprague–Dawley rats into five groups: control, LPS injury, LPS + low-dose NaHS (0.78 mg•kg-1), LPS + middle-dose NaHS (1.56 mg•kg-1), and LPS + high-dose NaHS (3.12 mg•kg-1). Rats were killed 3 h after NaHS administration. We calculated a semi-quantitative histological index of lung injury assessments and measured the lung wet-to-dry weight ratio. We further analyzed serum for interleukin-1β levels using enzyme-linked immunosorbent assays. We observed lung mitochondria ultrastructures with an electron microscope. We examined oxidative stress markers in lung mitochondria and the mitochondrial swelling and activity. We analyzed lung mitochondria and cytosol Cyt-c protein expression using Western blotting.ResultsCompared to the control group, the quantitative assessment score index, wet-to-dry weight ratios, and interleukin-1β content in the LPS injury group were significantly increased and the mitochondrial ultrastructure damaged. Furthermore, mitochondrial activity, adenosine triphosphatease, superoxide dismutase, glutathione peroxidase, and mitochondrial Cyt-c protein expression were significantly decreased, and malondialdehyde content, mitochondrial swelling, and cytosol Cyt-c protein expression were significantly increased in the LPS injury group compared to the control group. These effects were lessened by NaHS.ConclusionExogenous H2S provided a protective effect against ALI by decreasing the mitochondrial lipid peroxidation level and protecting the cell structure in the LPS-induced rat models. Its regulatory effect on lung mitochondria is positively correlated with the dosage.

Use of Lung Ultrasound to Assess the Efficacy of an Alveolar Recruitment Maneuver in Rabbits With Acute Respiratory Distress Syndrome

“…Ten high-power fields were randomly selected from the anterior, median, and posterior regions of the lung section and scored according to the system of Smith et al, 11 which was semiquantitative and designed to compare various tissue damage microscopically. 12,13 According to this system, an independent pathologist assessed alveolar and interstitial inflammation, alveolar and interstitial hemorrhage, lung edema, atelectasis, necrosis, and the degree of hyaline membrane formation and assigned a score of 0, 1, 2, or 3 for each parameter, corresponding to no, mild, moderate, or severe changes, respectively. The mean score of 10 highpower fields for each region was calculated.…”

Mitochondria Targeted Peptide Attenuates Mitochondrial Dysfunction, Controls Inflammation and Protects Against Spinal Cord Injury-Induced Lung Injury

“…Mitochondrial dysfunction is closely associated with lung injury [15, 16]. Regulation of mitochondrial dysfunction attenuates lung tissue damage [13, 14]. In the present study, we analyzed microglia polarization using mtDNA copy number, ATP synthases, and the release of cytosolic Cyt C based on a previous study [12, 33].…”

“…Mitochondrial dysfunction leads to increased ROS production, mitochondrial DNA damage (copy number reduction and mutation), and disorders of oxidative phosphorylation of the mitochondrial respiratory chain [12, 13]. Previous reports have shown mitochondrial dysfunction, which is important for energy metabolism, inflammatory responses, oxidative stress, the intrinsic apoptotic pathway, plays a substantial role in lung injury [14, 15]. Moreover, mitochondrial DNA provokes systemic inflammation in lipopolysaccharide (LPS)-induced lung injury in rats [15].…”

Environmental toxicology of hydrogen sulfide

“…Also, in various other animal models, sulfide has been demonstrated to contribute to the development and progression of lung inflammation and injury [161]. Bizarrely and to the contrary, however, sulfide is apparently ameliorative in the case of lipopolysaccharide-induced acute lung-injury (ALI) in rats [162] and in burn/smoke-induced ALI in sheep[8]. Both Olson [130, 131] and Haouzi [163] have written extensively about the practicalities of manipulating sulfide in biological samples and the difficulty in distinguishing physiological from pharmacological processes, particularly at the uncertain sulfide levels obtained in tissues irrespective of the method of administration.…”