A complex antioxidant system has been developed in mammals to relieve oxidative stress. However, excessive reactive species derived from oxygen and nitrogen may still lead to oxidative damage to tissue and organs. Oxidative stress has been considered as a conjoint pathological mechanism, and it contributes to initiation and progression of liver injury. A lot of risk factors, including alcohol, drugs, environmental pollutants and irradiation, may induce oxidative stress in liver, which in turn results in severe liver diseases, such as alcoholic liver disease and non-alcoholic steatohepatitis. Application of antioxidants signifies a rational curative strategy to prevent and cure liver diseases involving oxidative stress. Although conclusions drawn from clinical studies remain uncertain, animal studies have revealed the promising in vivo therapeutic effect of antioxidants on liver diseases. Natural antioxidants contained in edible or medicinal plants often possess strong antioxidant and free radical scavenging abilities as well as anti-inflammatory action, which are also supposed to be the basis of other bioactivities and health benefits. In this review, PubMed was extensively searched for literature research. The keywords for searching oxidative stress were free radicals, reactive oxygen, nitrogen species, anti-oxidative therapy, Chinese medicines, natural products, antioxidants and liver diseases. The literature, including ours, with studies on oxidative stress and anti-oxidative therapy in liver diseases were the focus. Various factors that cause oxidative stress in liver and effects of antioxidants in the prevention and treatment of liver diseases were summarized, questioned, and discussed.

/pdf/the-role-of-oxidative-stress-and-antioxidants-in-liver-3pnddyz5af.pdf

The Role of Oxidative Stress and Antioxidants in Liver Diseases

Myocardial fibrosis is a significant global health problem associated with nearly all forms of heart disease. Cardiac fibroblasts comprise an essential cell type in the heart that is responsible for the homeostasis of the extracellular matrix; however, upon injury, these cells transform to a myofibroblast phenotype and contribute to cardiac fibrosis. This remodeling involves pathological changes that include chamber dilation, cardiomyocyte hypertrophy and apoptosis, and ultimately leads to the progression to heart failure. Despite the critical importance of fibrosis in cardiovascular disease, our limited understanding of the cardiac fibroblast impedes the development of potential therapies that effectively target this cell type and its pathological contribution to disease progression. This review summarizes current knowledge regarding the origins and roles of fibroblasts, mediators and signaling pathways known to influence fibroblast function after myocardial injury, as well as novel therapeutic strategies under investigation to attenuate cardiac fibrosis.

/pdf/cardiac-fibrosis-the-fibroblast-awakens-3nvjgzenz5.pdf

Cardiac Fibrosis: The Fibroblast Awakens.

Cell surface receptors forgibbon apeleuke- miavirus (Glvr-1) andmarine amphotropic retrovirus (Ram-i) aredistinct butrelated proteins having multiple membrane- nning regions. Distant homology with aputative phosphate permease ofNeurospora crussa suggested that these receptors might serve transport functions. Byexpression inXenopus laevis oocytes andinmam l cells, wehaveidentified Glvr-1 andRam-iassodium-dependent phosphate symport- ers. Two-electrode voltage-camp analysis indicates netcation influx, gestngthatphosphate istransported withexcess sodium ions. Phosphate uptake wasreduced by>50%in mousefibroblasts expressing amphotropic envelope glycopro- tein, which binds toRam-i, indicating that Ram-iIsamajor phosphate transporter inthese cells. RNAanalysis shows wide butdistinct tissue distributions, withGlvr-1 expression being highest inbonemarrowandRam-i inheart. Overexpression of Ram-i severely reprsdGlvr-i synthesis infibroblasts, sug- gesting that transporter expression maybecontrolled bynet phosphate accumulation. Accordingly, depletion ofextracellu- larphosphate increased Ram-iandGlvr-i expression 3-to 5-fold. Theseresults suggest simple methods tomodulate retroviral receptor expression, withpossible applications to humangenetherapy. Keyissues invirology havebeenidentification ofcell-surface virus receptors, determination ofreceptor expression pat- terns, andelucidation oftheeffects ofinfection onthenormal functions ofthese molecules. Theseissues arecritical inthe caseofretroviruses because cells canbecomechronically infected, leading toreceptor down-modulation andsubse- quentderangements incellular functions. Forexample, the CD4receptor forhumanimmunodeficiency virus (HIV) is important forhelper T-cell function, andinterference with this normal function isanimportant aspect ofHIV-induced disease (1). Indeed, three genes ofHIV(env, nef, andvpu) caneachmediate CD4down-modulation (1-4). Whileseveral retroviral receptor cDNAshavebeeniso- lated (5-11), theonly functionally characterized receptors are theabove-mentioned CD4forHIVandasodium-indepen- dentcationic aminoacidtransporter forecotropic murine leukemia viruses (MLVs)(12, 13). Amongthecloned recep- tors with unknown functions arethose that mediate infections ofgibbon apeleukemia virus (GALV)andofmouseampho- tropic retrovirus (these receptors aretermed Glvr-1 and Ram-1,respectively) (7,10,11). Glvr-1 andRam-1are distinct proteins withmultiple hydrophobic potential mem- brane-spanning sequences. Although theycontain large un- related central domains, theyshare about60%overall se- quence identity andhaveabout 25%identity withaputative phosphate permease ofNeurospora crassa (10, 11,14,15). These data suggested that Glvr-1 andRam-1might betrans- porters; however, their solute specificities couldnotbe inferred because evenclosely related transport proteins often carry unrelated solutes (12, 13,16,17). Weidentified thetransporter activities ofGlvr-i andRam-1 byasystematic approach that involved expression ofthese proteins inXenopus laevis oocytes andmeasurement of transmembrane currents during exposure oftheoocytes to different salts andnutrients. Ourresults indicate that Glvr-1 andRam-1aresodium/phosphate symporters andthat these proteins provide amajor pathway forphosphate uptake into manymammalian cells. Inaddition, wehaveshownthat phosphate transport rates areaffected bothbyretroviral infection andbychanges inextracellular phosphate levels. MATERIALSANDMETHODS Cell Lines andRetroviral Vectors. Cell lines usedincluded 208Fratembryo fibroblasts (18), PA317cells (19), andNIH 3T3thymidine kinase-minus mouseembryo fibroblasts (20) andderivatives. Cells weregrowninDulbecco's minimal essential mediumwith10%o (vol/vol) fetal bovine serum. Retroviral vectors encoding neomycin phosphotransferase andratRam-1, humanGlvr-1, themouseecotropic receptor Rec-i, orhumanclotting factor IXweremadebycloning the respective cDNAsinto theretroviral vector LXSN(21). Vectors weretransfected into PA317retrovirus packaging cells (19), andtransiently produced virus washarvested after 2daysandwasusedtotransduce 208Fratfibroblasts as described (21) except fortheclotting factor IXvirus, which washarvested fromapreviously described stable vector- producing cell line (22). Transduced cells weregrowninthe presence ofG418toselect forcells expressing thevectors. Ion-Transport Assays inXenopus Oocytes Injected with Retrovirus Receptor RNAs.Thecoding regions oftherat Ram-i (10) andhumanGlvr-1 (7)cDNAswerecloned into pGEM-7Z(Promega) withtheir 5'endsadjacent totheSP6 promoter. FormRNA synthesis, theplasmids werelinear- ized andtranscribed withSP6polymerase inthepresence of m7G(5')ppp(5')G capsaccording tothemanufacturer's direc- tions (Pharmacia). Xenopus laevis oocytes wereinjected with 50nlofmRNA (1ng/nl) orwith anequal volume ofH20and wereincubated for4-6daysat17'C; thentwo-microelec- trode voltage-clamp recordings orradiolabel uptake assays

Cell-surface receptors forgibbon apeleukemia virus and amphotropic murineretrovirus areinducible sodium-dependent phosphate symporters

The SLC2 family of glucose and polyol transporters comprises 13 members, the glucose transporters (GLUT) 1–12 and the H+-myo-inositol cotransporter (HMIT) These proteins all contain 12 transmembrane domains with both the amino and carboxy-terminal ends located on the cytoplasmic side of the plasma membrane and a N-linked oligosaccharide side-chain located either on the first or fifth extracellular loop Based on sequence comparison, the GLUT isoforms can be grouped into three classes: class I comprises GLUT1–4; class II, GLUT6, 8, 10, and 12 and class III, GLUT5, 7, 9, 11 and HMIT Despite their sequence similarity and the presence of class-specific signature sequences, these transporters carry various hexoses and HMIT is a H+/myo-inositol co-transporter Furthermore, the substrate transported by some isoforms has not yet been identified Tissue- and cell-specific expression of the well-characterized GLUT isoforms underlies their specific role in the control of whole-body glucose homeostasis Numerous studies with transgenic or knockout mice indeed support an important role for these transporters in the control of glucose utilization, glucose storage and glucose sensing Much remains to be learned about the transport functions of the recently discovered isoforms (GLUT6–13 and HMIT) and their physiological role in the metabolism of glucose, myo-inositol and perhaps other substrates

/pdf/the-slc2-family-of-facilitated-hexose-and-polyol-3c5uaofv9u.pdf

The SLC2 family of facilitated hexose and polyol transporters

Carnitine is a conditionally essential nutrient that plays a vital role in energy production and fatty acid metabolism. Vegetarians possess a greater bioavailability than meat eaters. Distinct deficiencies arise either from genetic mutation of carnitine transporters or in association with other disorders such as liver or kidney disease. Carnitine deficiency occurs in aberrations of carnitine regulation in disorders such as diabetes, sepsis, cardiomyopathy, malnutrition, cirrhosis, endocrine disorders and with aging. Nutritional supplementation of L-carnitine, the biologically active form of carnitine, is ameliorative for uremic patients, and can improve nerve conduction, neuropathic pain and immune function in diabetes patients while it is life-saving for patients suffering primary carnitine deficiency. Clinical application of carnitine holds much promise in a range of neural disorders such as Alzheimer's disease, hepatic encephalopathy and other painful neuropathies. Topical application in dry eye offers osmoprotection and modulates immune and inflammatory responses. Carnitine has been recognized as a nutritional supplement in cardiovascular disease and there is increasing evidence that carnitine supplementation may be beneficial in treating obesity, improving glucose intolerance and total energy expenditure.

/pdf/role-of-carnitine-in-disease-168ymd2whv.pdf

Role of carnitine in disease

Antioxidant enzyme activity and lipid peroxidation in liver and kidney of rats exposed to microcystin-LR administered intraperitoneally

https://espace.library.uq.edu.au/view/UQ:8de62da/UQ8de62da_OA.pdf

Oxidative stress: Normal pregnancy versus preeclampsia

Background: Captopril is an angiotensin-converting enzyme (ACE) inhibitor widely used in the treatment of arterial hypertension and cardiovascular diseases. Our objective was to study whether captopril is able to attenuate the cardiac inflammatory process associated with arterial hypertension. Methods: Left ventricle mRNA expression and plasma levels of pro-inflammatory (interleukin-1β (IL-1β) and IL-6) and anti-inflammatory (IL-10) cytokines, were measured in spontaneously hypertensive rats (SHR) and their control normotensive, Wistar-Kyoto (WKY) rats, with or without a 12-week treatment with captopril (80 mg/Kg/day; n = six animals per group). To understand the mechanisms involved in the effect of captopril, mRNA expression of ACE, angiotensin II type I receptor (AT1R) and p22phox (a subunit of NADPH oxidase), as well as NF-κB activation and expression, were measured in the left ventricle of these animals. Results: In SHR, the observed increases in blood pressures, heart rate, left ventricle relative weight, plasma levels and cardiac mRNA expression of IL-1β and IL-6, as well as the reductions in the plasma levels and in the cardiac mRNA expression of IL-10, were reversed after the treatment with captopril. Moreover, the mRNA expressions of ACE, AT1R and p22phox, which were enhanced in the left ventricle of SHR, were reduced to normal values after captopril treatment. Finally, SHR presented an elevated cardiac mRNA expression and activation of the transcription nuclear factor, NF-κB, accompanied by a reduced expression of its inhibitor, IκB; captopril administration corrected the observed changes in all these parameters. Conclusion: These findings show that captopril decreases the inflammation process in the left ventricle of hypertensive rats and suggest that NF-κB-driven inflammatory reactivity might be responsible for this effect through an inactivation of NF-κB-dependent pro-inflammatory factors.

/pdf/captopril-reduces-cardiac-inflammatory-markers-in-23g1qzrqbp.pdf

Captopril reduces cardiac inflammatory markers in spontaneously hypertensive rats by inactivation of NF-kB

The role of inflammatory markers in the cardioprotective effect of L-carnitine in L-NAME-induced hypertension.

Comparative effects of captopril and l-carnitine on blood pressure and antioxidant enzyme gene expression in the heart of spontaneously hypertensive rats

Alfonso Mate

Papers

Antioxidant enzyme activity and lipid peroxidation in liver and kidney of rats exposed to microcystin-LR administered intraperitoneally

Oxidative stress: Normal pregnancy versus preeclampsia

Captopril reduces cardiac inflammatory markers in spontaneously hypertensive rats by inactivation of NF-kB

The role of inflammatory markers in the cardioprotective effect of L-carnitine in L-NAME-induced hypertension.

Comparative effects of captopril and l-carnitine on blood pressure and antioxidant enzyme gene expression in the heart of spontaneously hypertensive rats