title: Hydrogen-Rich Saline Attenuates Lipopolysaccharide-Induced Heart Dysfunction by Restoring Fatty Acid Oxidation in Rats by Mitigating C-Jun N-Terminal Kinase Activation.
abstract: Sepsis is common in intensive care units (ICU) and is associated with high mortality. Cardiac dysfunction complicating sepsis is one of the most important causes of this mortality. This dysfunction is due to myocardial inflammation and reduced production of energy by the heart. A number of studies have shown that hydrogen-rich saline (HRS) has a beneficial effect on sepsis. Therefore, we tested whether HRS prevents cardiac dysfunction by increasing cardiac energy. Four groups of rats received intraperitoneal injections of one of the following solutions: normal saline (NS), HRS, lipopolysaccharide (LPS), and LPS plus HRS. Cardiac function was measured by echocardiography 8 h after the injections. Gene and protein expression related to fatty acid oxidation (FAO) were measured by quantitative polymerase chain reaction (PCR) and Western blot analysis. The injection of LPS compromised heart function through decreased fractional shortening (FS) and increased left ventricular diameter (LVD). The addition of HRS increased FS, palmitate triphosphate, and the ratio of phosphocreatinine (PCr) to adenosine triphosphate (ATP) as well as decreasing LVD. The LPS challenge reduced the expression of genes related to FAO, including perioxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), perioxisome proliferator-activated receptor alpha (PPARα), Estrogen-related receptor alpha (ERRα), and their downstream targets, in mRNA and protein level, which were attenuated by HRS. However, HRS had little effect on glucose metabolism. Furthermore, HRS inhibited c-Jun N-terminal kinase (JNK) activation in the rat heart. Inhibition of JNK by HRS showed beneficial effects on LPS-challenged rats, at least in part, by restoring cardiac FAO.
authors.affiliation: *Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, P.R. China †Department of Anesthesiology, General Hospital of Shenyang Military Region, Shenyang, P.R. China.
authors.forename: Bingdong
authors.initials: B
authors.lastname: Tao
authors.forename: Lidan
authors.initials: L
authors.lastname: Liu
authors.forename: Ni
authors.initials: N
authors.lastname: Wang
authors.forename: Dongyi
authors.initials: D
authors.lastname: Tong
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D000818:Animals; D004452:Echocardiography; D005227:Fatty Acids / Q000737:chemistry*; D006321:Heart / Q000503:physiopathology*; D006331:Heart Diseases / Q000139:chemically induced / Q000503:physiopathology / Q000628:therapy*; D006352:Heart Ventricles / Q000503:physiopathology; D006859:Hydrogen / Q000737:chemistry; D007249:Inflammation; D007274:Injections, Intraperitoneal; D007362:Intensive Care Units; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010100:Oxygen / Q000737:chemistry*; D047493:PPAR alpha / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010725:Phosphocreatine / Q000031:analogs & derivatives / Q000378:metabolism; D016133:Polymerase Chain Reaction; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000503:physiopathology*; D012965:Sodium Chloride / Q000737:chemistry*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D008070:Lipopolysaccharides; D047493:PPAR alpha; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D014157:Transcription Factors; D010725:Phosphocreatine; D012965:Sodium Chloride; C025403:phosphocreatinine; D006859:Hydrogen; D000255:Adenosine Triphosphate; D048031:JNK Mitogen-Activated Protein Kinases; D010100:Oxygen