Zhouheng Ye

Methane attenuates myocardial ischemia injury in rats through anti-oxidative, anti-apoptotic and anti-inflammatory actions.

Myocardial infarction (MI) remains the most frequent cardiovascular disease with high mortality. Recently, methane has been shown protective effects on small intestinal ischemia-reperfusion injury. We hypothesized that methane-rich saline (MS) could protect the myocardium again MI via its anti-oxidative, anti-apoptotic and anti-inflammatory effects. In experiment 1, tetrazolium chloride staining and detection of myocardial enzymes and oxidative and inflammatory parameters were performed at 12h after MI to determine the optimal dose at which intraperitoneal MS exerted the best protective effects on MI. In experiment 2, rats were treated with 10 ml/kg MS. Myocyte apoptosis was detected 72 h after MI, and cardiac function and myocardial remodeling were evaluated 4 weeks after MI. Results showed different dose of MS reduced infarct area, decreased myocardial enzymes, inhibited inflammation and oxidative stress following MI. The optimal dose of MS was 10 mg/kg. Moreover, treatment with 10mg/kg MS for 3 days significantly reduced myocyte apoptosis, improved cardiac function and inhibited myocardial remodeling (reduced anterior wall thickness, attenuated myocyte hypertrophy, and decreased myocardial collagen). MS protects the myocardium of MI rats via its anti-oxidative, anti-inflammatory, anti-apoptotic and anti-remodeling activities. Thus, MS provides a novel and promising strategy for the treatment of ischemic heart diseases.

Methane Attenuates Hepatic Ischemia/Reperfusion Injury in Rats Through Antiapoptotic, Anti-Inflammatory, and Antioxidative Actions.

ABSTRACT Hepatic ischemia/reperfusion (I/R) injury, which occurs in various diseases, introduces severe tissue damage and liver dysfunction. However, no promising therapies for such a significant condition currently exist. Methane has been suggested to exert a protective effect against intestinal I/R injury. In this study, we introduced methane to treat hepatic I/R injury to show its promising protective effect. Also, intraperitoneal injection with methane-rich saline, which could have potential clinical applications, was applied as a new method. Partial liver warm ischemia was applied in Sprague-Dawley rats for 60 min followed by succedent reperfusion. In the test for effective dosage, methane-rich saline was administrated intraperitoneally to the rats at doses of 1, 5, 20, or 40 mL/kg at onset of reperfusion. In the test for protective effect, rats received methane-rich saline intraperitoneally at a dose of 10 mL/kg before the initiation of reperfusion. We found that methane-rich saline significantly decreased serum alanine aminotransferase, aspartate aminotransferase activity, and the occurrence of necrosis. Moreover, methane-rich saline reduced the amount of caspase-3 and the number of apoptotic cells. In addition, methane-rich saline increased the level of superoxide dismutase and decreased the level of malondialdehyde and 8-hydroxyguanosine. Furthermore, research indicated that methane-rich saline markedly decreased gene expression and content of tumor necrosis factor-&agr; and interleukin-6. Also, reduced CD68-positive cells showed decreased inflammatory cells in the liver. Our results suggest that methane protects the liver against I/R injury through antiapoptotic, antioxidative, and anti-inflammatory actions.

Helium preconditioning protects mouse liver against ischemia and reperfusion injury through the PI3K/Akt pathway

BACKGROUND & AIMS Hepatic ischemia and reperfusion (I/R) injury is a major complication of liver transplantation, hepatic resection and trauma. Helium preconditioning (HPC) exerts protection against ischemic stress. We investigated potential beneficial effects of HPC on I/R-induced liver injury and investigated mechanisms underlying HPC-induced protection. METHODS We employed a model of segmental warm hepatic I/R on BALB/c mice. Serum ALT was measured and livers were analysed by histology, RT-PCR and western blot. HPC was induced by inhalation of a 70% helium/30% oxygen mixture for three 5-min periods, interspersed with three 5-min washout periods by room air. We tested which component of HPC (the helium/air mixture inhalation, the air room gap, or the interaction between these two factors) is protective. RESULTS We found that HPC caused a significant increase in Akt phosphorylation in hepatocytes. The HPC-induced Akt phosphorylation resulted in decreased hepatocellular injury and improved survival rate of the treated animals. PI3K inhibitors abolished HPC induced effects. HPC-induced Akt phosphorylation affected expression of its downstream molecules. The effects of HPC on the PI3K/Akt pathway were attenuated by adenosine A2A receptor blockade, but could be re-established by PTEN inhibition. We demonstrated that the interaction of helium/air breathing and air gaps is responsible for the observed effects of HPC. CONCLUSIONS HPC may be a promising strategy leading to a decrease in I/R induced liver injury in clinical settings. Additionally, the PI3K/Akt pathway plays an essential role in the protective effects of HPC in hepatic I/R injury.

Neuroprotective effects of exogenous methane in a rat model of acute carbon monoxide poisoning.

OBJECTIVE Delayed neuropsychological sequelae (DNS) are the most common and serious effects of severe carbon monoxide (CO) poisoning, occurring in approximately half of all CO poisoning cases. Growing evidence suggests that oxidative stress and secondary reactions in delayed brain injury are crucial to CO toxicity, similar to ischaemia-reperfusion injury. Exogenous methane plays a protective role in ischaemia-reperfusion injury by affecting key events through anti-oxidant, anti-inflammatory, and anti-apoptosis actions. Our study aimed to explore the potential of exogenous methane to relieve the severity of DNS. METHODS Thirty-six male Sprague-Dawley (SD) rats were divided into three groups of normal-, CO- and CO plus methane-treated rats. The rats in the latter two groups were exposed to 1000 ppm CO for 40 min and then to 3000 ppm CO for another 20 min. Following CO exposure, saline or methane saline (10 ml/kg) was intraperitoneally administered to rats in the CO group or the CO plus methane group, respectively. On the ninth day after CO exposure, Morris water maze testing, histological analysis, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) and immunohistochemical labelling were performed on 6 rats in each group. The remaining 6 rats in each group were used to detect oxidative damage markers, inflammatory cytokines and apoptosis proteins. RESULTS Methane significantly improved CO-impaired pathological characteristics as well as learning and memory performance. In addition, methane significantly increased the superoxide dismutase (SOD) activity, lowered the CO-increased level of malondialdehyde (MDA) 3-nitrotyrosine (3-NT) and 8-hydroxy-2-deoxyguanosine (8-OHdG), inhibited levels of tumour necrosis factor-α (TNF-α), interleukin 1-β (IL1-β) and caspase-3 in the rat cerebral cortex and hippocampus but had no effect on IL-6 levels. CONCLUSION The hippocampus was the main target of CO-induced alterations in the rat brain compared to the cerebral cortex. Methane treatment protected the rat brain from the harmful effects induced by CO exposure and improved the outcome of DNS through anti-oxidant, anti-inflammatory and anti-apoptosis activities.

Progress in the study of biological effects of hydrogen on higher plants and its promising application in agriculture

While the medical effects of hydrogen have been broadly analyzed, research into the effects of hydrogen on higher plants has often been of lesser concern. Recent studies on the botanical effects of hydrogen have shown that it is involved in signal transduction pathways of plant hormones and can improve the resistance of plants to stressors, such as drought, salinity, cold and heavy metals. In addition, hydrogen could delay postharvest ripening and senescence of fruits. Observational evidence has also shown that hydrogen can regulate the flowering time of plants. These results indicate that hydrogen may have great potential applications within agricultural production, indicating that there may be a new ‘hydrogen agricultural era’ to come.

Bustling argon: biological effect.

Argon is a noble gas in group 18 of the periodic table. Certificated to exist in air atmosphere merely one century ago, discovery of argon shows interesting stories of researching and exploring. It was assumed to have no chemical activity. However, argon indeed present its biological effect on mammals. Narcotic effect of argon in diving operation and neur-protective function of argon in cerebral injury demonstrate that argon has crucial effect and be concentrated on is necessary. Furthermore, consider to be harmless to human, argon clinical application in therapy would be another option.

High-concentration hydrogen protects mouse heart against ischemia/reperfusion injury through activation of thePI3K/Akt1 pathway

The study investigated the role of Akt1 through the cardioprotection of high-concentration hydrogen (HCH). C57BL/6 mice were randomly divided into the following groups: sham, I/R, I/R + HCH, I/R + HCH + LY294002 (PI3K inhibitor), I/R + HCH + wortmannin (PI3K inhibitor), I/R + LY294002, and I/R + wortmannin. After 45 min of ischemia, HCH (67% H2 and 33% O2) was administered to mice during a 90-min reperfusion. To investigate the role of Akt1 in the protective effects of HCH, mice were divided into the following groups: I/R + A-674563 (Akt1 selective inhibitor), I/R + HCH + A-674563, I/R + CCT128930 (Akt2 selective inhibitor), and I/R + HCH + CCT128930. After a 4-h reperfusion, serum biochemistry, histological, western blotting, and immunohistochemical analyses were performed to evaluate the role of the PI3K-Akt1 pathway in the protection of HCH. In vitro, 75% hydrogen was administered to cardiomyocytes during 4 h of reoxygenation after 3-h hypoxia. Several analyses were performed to evaluate the role of the Akt1 in the protective effects of hydrogen. HCH resulted in the phosphorylation of Akt1 but not Akt2, and Akt1 inhibition markedly abolished HCH-induced cardioprotection. Our findings reveal that HCH may exert cardioprotective effects through a PI3K-Akt1-dependent mechanism.

Inhalation of high concentrations of hydrogen ameliorates liver ischemia/reperfusion injury through A2A receptor mediated PI3K-Akt pathway

Graphical abstract Figure. No Caption available. Background and aims: This study explored the hepatoprotection of high concentrations of hydrogen (HCH) inhalation in a mouse hepatic ischemia/reperfusion (I/R) injury model and the potential mechanism. Methods: To explore the role of the PI3K‐Akt pathway in the hepatoprotection of HCH, C57BL/6 mice were randomly divided into five groups: Sham, I/R, I/R + HCH, LY294002 (PI3K inhibitor) + I/R + HCH, and LY + I/R groups. Mice received inhalation of 66.7% hydrogen and 33.3% oxygen for 1 h immediately after surgery. LY294002 was intravenously injected at 10 mol/kg. To explore whether PI3K‐Akt pathway activation was mediated by the A2A receptor, additional four groups were included: ZM241385 (A2A receptor antagonist) + I/R + HCH, ZM241385 + I/R, bpv(HOpic) (PTEN inhibitor) + I/R, and ZM241385 + bpv + I/R + HCH. Six hours after I/R, serum biochemistry, histological examination, Western blotting, and immunohistochemistry were performed to evaluate the hepatoprotection of HCH and the role of the PI3K‐Akt pathway and A2A receptor in this protection. Results: Liver dysfunction, hepatic pathological injury, infiltration of inflammatory cytokines, and hepatocyte apoptosis were observed after hepatic I/R, accompanied by inhibition of the PI3K‐Akt pathway. HCH significantly improved liver function, reduced serum inflammatory cytokines, and inhibited hepatocyte apoptosis, and also induced the PI3K‐Akt pathway activation. In the presence of LY294002 or ZM241385, the protective effects of HCH were markedly attenuated, but the effects of ZM241385 were reversed by bpv(HOpic). Conclusion: Our findings indicate that HCH may protect the liver against I/R injury through the A2A dependent PI3K‐Akt pathway.

Characteristics of exogenous carbon monoxide deliveries.

Carbon monoxide (CO) has long been considered an environmental pollutant and a poison. Exogenous exposure to amounts of CO beyond the physiologic level of the body can result in a protective or adaptive response. However, as a gasotransmitter, endogenous CO is important for multiple physiologic functions. To date, at least seven distinct methods of delivering CO have been utilized in animal and clinical studies. In this mini-review, we summarize the exogenous CO delivery methods and compare their advantages and disadvantages.

Hypoxia therapy--a new hope for the treatment of mitochondrial dysfunctions.

Mitochondrial dysfunctions are characteristic features of numerous diseases and play a critical role in disease pathogenesis. Despite intensive research in this area, there are no approved therapies that directly target mitochondria. Recently a study by Jain et al. from Massachusetts General Hospital, USA reported the effectiveness of hypoxia for treatment of mitochondrial disease in mice. In this commentary, we summarized the potential mechanisms underlying the therapeutic effects of hypoxia on mitochondrial dysfunction, and clinical limitations of hypoxia as a therapy for human patients. We hope that our concerns will be helpful for further clinical studies addressing moderate hypoxia in mitochondrial dysfunction.