Effects of hydrogen-rich saline on platelet activation in hypertensive rats

OBJECTIVE To investigate the effect of hydrogen-rich saline on platelet activation in hypertensive rats.METHODS The male Wistar rats were divided into control group,hypertension group,control+hydrogen-rich saline group and hypertension+hydrogen-rich saline group.Hypertension was induced by subcutaneous infusion with angiotensinⅡ0.7 mg·kg-1·d-1for 2 weeks by osmotic mini-pumps in rats.Hydrogen-rich saline(10 mL·kg-1·d-1)was administered by intraperitoneal injection for 14 d.Platelet adhesion on collagen surface was evaluated using a well-defined perfusion chamber at low shear rate(300s-1)and high shear rate(1080s-1).The maximum aggregation rate of platelets induced by ADP was determined by turbidimetry.The levels of reactive oxygen species(ROS),nitric oxide(NO)and Ca2+in platelets were measured with flow cytometry.RESULTS When compared with the control group,platelet aggregation,platelet adhesion rate in high shear rate and low shear rate,and the level of ROS and Ca2+in platelets were elevated in hypertensive group.However,NO level in platelets decreased.Compared with the hypertensive group,hydrogen-rich saline treatment decreased platelet aggregation,platelet adhesion rate,the levels of ROS and Ca2+in platelets,and increased NO level in platelets of hypertensive rats.CONCLUSION Hydrogen-rich saline could inhibit platelet activation in hypertensive rats.This effect may be related to antioxidative stress.

Hydrogen-rich Saline Reduces Atherogenesis in Apolipoprotein E Knockout Mice Fed a High-fat Diet by Inhibiting the Non-HDL-mediated Arterial Inflammation and Promoting the Expression of Genes Involving Reverse Cholesterol Transport

Aim Hydrogen(dihydrogen,H2) is an effective antioxidant to reduce oxidative stress and oxidative stress is implicated in atherogene-sis.In this study we examined whether hydrogen-saturated saline can prevent atherosclerosis in apolipoprotein E knockout(apoE-/-) mice fed either chowdiet or high-fat diet,and characterized the underlying molecular mechanisms.Methods and Results The atherosclerotic lesion formation displayed by oil red O staining positive area was reduced significantly in either aortic root section or aortic arch en face in hydrogen administrated apoE-/-mice fed either chowdiet or high-fat diet,compared to the control.Plasma analysis by enzymatic method showed that total cholesterol(TC) and non-high-density lipoprotein cholesterol(non-HDL-C)were remarkably decreased by treatment with hydrogen.Western blot analysis revealed a significant decrease of both plasma apoli-poprotein B(apoB) level and hepatic expression of apoB after hydrogen treatment,suggesting hydrogen could downregulate the expression of the major protein constituent of non-HDL.In addition,spectrophotometric measurement showed that plasma levels of malondi-aldehyde(MDA) and serum amyloid Awas decreased and paraoxonase-1 activity was increased in mice treated with hydrogen,suggesting plasma lipid oxidation and peroxidation was impaired by hydrogen treatment.Besides,the MDA content of the non-HDL,whichseparated by ultracentrifugation from the plasma of mice treated with and without hydrogen,was reduced by hydrogen,suggesting the oxidation of non-HDL was impaired by hydrogen.Moreover,we found hydrogen treatment significantly suppressed the production of tumor necrosis factor-α(TNF-α) and interleukin-6 in RAW264.7 macrophages after stimulation with the isolated non-HDL,suggesting hydrogen reduces atherogenesis by inhibiting non-high-density lipoprotein(HDL)-mediated inflammation.Furthermore,immunohis-tochemistry of aortic valve sections revealed that hydrogen attenuated lesion formation by suppressing the expression of several proin-flammatory factors and decreasing vessel wall infiltration of macrophages,indicating hydrogen-treatment reduces arterial inflammation.Besides,real-time PCR and western blot analysis disclosed that the expression of several transporter genes involved in the process ofreverse cholesterol transport,including hepatic scavenger receptor class B type I(SR-BI),ATP-binding cassette(ABC) transporters ABCG8,ABCB4,ABCB11,and macrophage SR-BI,were all induced by hydrogen treatment.Conclusion These results re-vealed that administration of hydrogen-rich saline reduces atherogenesis in apoE-/-mice fed a high-fat diet by inhibiting the non-HDL-mediated arterial inflammation and promoting the expression of genes involving reverse cholesterol transport.

SR-BI Associates with ABCG1 and Inhibits ABCG1-mediated Cholesterol Efflux from Cells to HDL3

Reverse cholesterol transport(RCT)is assumed to play a critical role in the pathogenesis of atherosclerosis.Cellular cholesterol efflux,by which cholesterol is transported from peripheral cells to high-density lipoprotein(HDL)

Neuroprotective Effects of Molecular Hydrogen:A Critical Review

Molecular hydrogen(H_(2))is a physiologically inert gas.However,during the last 10 years,increasing evidence has revealed its biological functions under pathological conditions.More specifically,H_(2) has protective effects against a variety of diseases,particularly nervous system disorders,which include ischemia/reperfusion injury,traumatic injury,subarachnoid hemorrhage,neuropathic pain,neurodegenerative diseases,cognitive dysfunction induced by surgery and anesthesia,anxiety,and depression.In addition,H_(2) plays protective roles mainly through anti-oxidation,anti-inflammation,antiapoptosis,the regulation of autophagy,and preservation of mitochondrial function and the blood-brain barrier.Further,H_(2) is easy to use and has neuroprotective effects with no major side-effects,indicating that H_(2) administration is a potential therapeutic strategy in clinical settings.Here we summarize the H_(2) donors and their pharmacokinetics.Meanwhile,we review the effectiveness and safety of H_(2) in the treatment of various nervous system diseasesbased on preclinical and clinical studies,leading to the conclusion that H_(2) can be a simple and effective clinical therapy for CNS diseases such as ischemia-reperfusion brain injury,Parkinson's disease,and diseases characterized by cognitive dysfunction.The potential mechanisms involved in the neuroprotective effect of H_(2) are also analyzed.

Surf4,cargo trafficking,lipid metabolism,and therapeutic implications

Surfeit 4 is a polytopic transmembrane protein that primarily resides in the endoplasmic reticulum(ER)membrane.It is ubiquitously expressed and functions as a cargo receptor,mediating cargo transport from the ER to the Golgi apparatus via the canonical coat protein complex Il(CoPll)-coated vesicles or specific vesicles.It also participates in ER-Golgi protein trafficking through a tubular network.Meanwhile,it facilitates retrograde transportation of cargos from the Golgi apparatus to the ER through Coplcoated vesicles.Surf4 can selectively mediate export of diverse cargos,such as PCSK9 very low-density lipoprotein(VLDL),progranulin,α1-antitrypsin,STING,proinsulin,and erythropoietin.It has been implicated in facilitating VLDL secretion,promoting cell proliferation and migration,and increasing replication of positive-strand RNA viruses.Therefore,Surf4 plays a crucial role in various physiological and pathophysiological processes and emerges as a promising therapeutic target.However,the molecular mechanisms by which Surf4 selectively sorts diverse cargos for ER-Golgi protein trafficking remain elusive.Here,we summarize the most recent advances in Surf4,focusing on its role in lipid metabolism.