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At least 973 records · Page 54Linked to original sources
PubMedDate not supplied

Salvia miltiorrhiza inhibits intimal hyperplasia and monocyte chemotactic protein-1 expression after balloon injury in cholesterol-fed rabbits.

Antioxidants that prevent low density lipoproteins (LDL) from oxidation may inhibit atherosclerosis and post-angioplasty restenosis. Salvia miltiorrhiza (SM) has been shown to inhibit LDL oxidation and reduce atherosclerosis in cholesterol-fed rabbits. The effects of SM on neointimal hyperplasia and monocyte chemotactic protein-1 (MCP-1) expression after balloon injury were studied. Male New Zealand white rabbits were fed a 2% cholesterol diet together with daily SM (4.8 gm/kg body wt.) treatment (SM; n=10) or without SM as a control (C; n=9) for 6 weeks. Probucol-treated (0.6 gm/kg body wt.) rabbits (P; n=9) were used as a positive control group. A balloon injury of the abdominal aorta was performed at the end of the third week. Aortas were harvested at the end of 6 weeks. The plasma cholesterol levels were lowered in SM group. The neointimal hyperplasia in abdominal aortas was significantly inhibited in SM group [neointima/media area ratio: 0.63+/-0.05 (SM) versus 0.78+/-0.05 (C); P < 0.05] and in P group [0.45+/-0.02 (P) versus 0.78+/-0.05 (C); P < 0.05] when compared with C group. SM treatment significantly reduced MCP-1 mRNA and protein expression in balloon-injured abdominal aorta. These inhibitory effects on intimal response after balloon injury might be attributed to antioxidant capacity and cholesterol lowering effect of SM. SM treatment may offer some protection against post-angioplasty restenosis.

Angioplasty, Balloon↗
PubMed1993

Lipoprotein oxidation and measurement of thiobarbituric acid reacting substances formation in a single microtiter plate: its use for evaluation of antioxidants.

Transition metals catalyze free radical-mediated oxidation of lipids and lipoproteins. This process is currently studied because of its potential relevance to pathological processes like atherosclerosis. Formation of thiobarbituric acid-reacting substances from polyenoic fatty acids is frequently used to follow oxidation of lipids and plasma lipoproteins. We describe here how Cu(II)- and Fe(III)-catalyzed oxidation of human low density lipoprotein or soy bean phospholipids and the photometric evaluation of the thiobarbituric acid-reaching substances formed can be conducted in the same 96-well microtiter plate. The procedure showed a correlation of 0.98 with conventional two-stage fluorimetric and spectrophotometric methods and also showed better reproducibility. The plate method can handle up to one plate per hour with considerably less labor than the test tube assays. The plate procedure required small volumes of diluted samples of lipoproteins lipids and reagents. The method was suitable for testing the concentration-dependent antioxidant potency of substances like probucol, butylated hydroxytoluene, and alpha-tocopherol. The method can also be used to follow the kinetics of oxidation of lipoproteins.

Antioxidants↗
PubMed1998

A fluorometric method for measurement of peroxyl radical scavenging activities of lipophilic antioxidants.

A fluorometric method for evaluation of activities of lipophilic antioxidants toward peroxyl radicals in a lipophilic medium (octane:butyronitrile; 9:1, v/v) and dioleoylphosphatidyl choline (DOPC) liposomal suspension in Tris-HCl buffer (pH 7.4 at 40 degrees C) has been developed. This fluorometric method is based on the use of the fatty acid 4,4-difluoro-5-(4-phenyl-1, 3-butadienyl)-4-bora-3a,4a-diaza-s-indacene-3-undec anoic acid (BODIPY 581/591 C11) as an indicator, 2,2'-azobis-2,4-dimethyl valeronitrile (AMVN) as a peroxyl radical generator, and 6-hydroxy-2, 5,7,8-tetramethyl chroman-2-carboxylic acid (Trolox) as a calibrator. In the absence of antioxidants, a linear correlation was found between the fluorescence decay of BODIPY 581/591 C11 and the concentration of AMVN. Trolox was used as a standard reference material for validating this newly developed method. A linear correlation was found between the net protection of the fluorescence of BODIPY 581/591 C11 and the amounts of added Trolox. Employing this method, the relative peroxyl radical scavenging activities of Trolox, alpha-tocopherol, alpha-carotene, beta-carotene, lutein, and probucol in octane:butyronitrile (9:1, v/v) were determined to be 1. 0:0.7:0.5:0.3:0.4:0.3. In the DOPC system, beta-carotene showed an antioxidant activity which is a factor of two greater than that of alpha-tocopherol. This assay is suitable for measurement of activities of antioxidants in an organic lipid environment and a liposomal medium.

Antioxidants↗
PubMed1997

Troglitazone has a scavenging effect on reactive oxygen species.

Troglitazone (CS-045), a newly developed antidiabetic thiazolidinedione that enhances insulin sensitivity, is similar in structure to several antioxidants, including alpha-tocopherol and probucol. The in vitro antioxidant activity of troglitazone has been demonstrated in alloxan-induced hyperlipoperoxidemic and hyperlipidemic mice. In this study, we found that troglitazone had a scavenging effect on reactive oxygen produced by xanthine-xanthine oxidase and generated by stimulated neutrophils and tends to be the radical form. Our results suggest that troglitazone is an antioxidant similar to alpha-tocopherol. However, under the same conditions, pioglitazone, another thiazolidinedione drug, did not have a scavenging effect. The antioxidant action of troglitazone, which is attributable to the similarity of its molecular structure to that of alpha-tocopherol, may be of benefit in preventing diabetic vascular complications, in addition to having hypoglycemic and hypolipidemic effects.

Antioxidants↗
PubMed1998

Lycopene in association with alpha-tocopherol inhibits at physiological concentrations proliferation of prostate carcinoma cells.

The effect of lycopene alone or in association with other antioxidants was studied on the growth of two different human prostate carcinoma cell lines (the androgen insensitive DU-145 and PC-3). It was found that lycopene alone was not a potent inhibitor of prostate carcinoma cell proliferation. However, the simultaneous addition of lycopene together with alpha-tocopherol, at physiological concentrations (less than 1 microM and 50 microM, respectively), resulted in a strong inhibitory effect of prostate carcinoma cell proliferation, which reached values close to 90 %. The effect of lycopene with alpha-tocopherol was synergistic and was not shared by beta-tocopherol, ascorbic acid and probucol.

Antioxidants↗
PubMed1998

Carvedilol inhibits endothelin-1 biosynthesis in cultured human coronary artery endothelial cells.

Carvedilol, a multiple action neurohumoral antagonist, has been reported recently to significantly reduce mortality in congestive heart failure (CHF) patients. In addition to being a beta-adrenoceptor antagonist, one of the unique aspects of the biological effects of carvedilol is that it is also a potent antioxidant with antimitogenic properties. As there is a significant correlation between plasma immunoreactive endothelin-1 (ET-1) levels and the severity of CHF, the present study was designed to determine the effects of carvedilol on ET-1 biosynthesis in cultured human coronary artery endothelial cells (HCAECs). HCAECs were treated with carvedilol 15 min prior to the addition of serum and ET-1 levels were measured in the cell culture conditioned medium 24 h later. Carvedilol (10 microM) significantly inhibited basal ET-1 production in HCAECs by 62 +/- 8%. Carvedilol produced a concentration-dependent inhibition of serum-mediated stimulation of ET-1 biosynthesis with an IC50 = 1.2 microM. PreproET-1 mRNA expression was also inhibited by carvedilol. Other beta-adrenoceptor antagonists, such as propranolol (10 microM) or celiprolol (10 microM), did not effect ET-1 biosynthesis. Furthermore, the antioxidant probucol (10 microM) did not effect ET-1 production. Immunohistochemical analysis of HCAECs demonstrated that resting HCAECs have expression of ET-1 and can be inhibited by carvedilol. The results of the present study demonstrate that serum stimulation of HCAECs produced an increase in ET-1 expression, and carvedilol treatment caused a marked decrease in stimulated ET-1 expression as compared to serum-treated HCAECs. These data indicate that carvedilol directly inhibits the biosynthesis of ET-1 in HCAECs, and this effect may contribute to its vasodilating and antiproliferative actions. Furthermore, these effects may contribute to the ability of carvedilol to improve clinical outcome in CHF patients.

Adrenergic beta-Antagonists↗
PubMed2001

Endothelin-1 synthesis and endothelin B receptor expression in human coronary artery smooth muscle cells and monocyte-derived macrophages is up-regulated by low density lipoproteins.

Endothelin-1 (ET-1) is a potent vasoconstrictive peptide exerting its effects predominantly by paracrine and autocrine mechanisms. ET-1 acts as a mitogen and co-mitogen on vascular smooth muscle cells, and accumulating evidence suggests that ET-1 is involved in the pathogenesis of atherosclerosis. Deposition of low density lipoproteins (LDL) in the vessel wall is known to play a crucial role in the development of atherosclerotic lesions. In the present study, we have investigated the effect of native LDL (nLDL) and oxidatively modified LDL (oxLDL) on ET-1 synthesis and endothelin receptor expression in cultured human coronary artery smooth muscle cells and human monocyte-derived macrophages. Native LDL and oxLDL induced a significant stimulation of ET-1 release and ET-1 mRNA expression in human coronary artery smooth muscle cells and monocyte-derived macrophages. Antibodies against the scavenger receptor CD36 significantly reduced the oxLDL-induced stimulation of ET-1 synthesis. The antioxidants trolox and probucol did not significantly inhibit the LDL-induced rise of ET-1 release. Endothelin B receptor expression was up-regulated in both cell types after incubation with nLDL and oxLDL. In coronary smooth muscle cells, endothelin A receptor expression was slightly increased by LDL, whereas endothelin A receptor was not detectable in monocyte-derived macrophages. Coronary artery smooth muscle cells secreted a more than 150-fold higher amount of immunoreactive ET-1 into the cell culture medium than monocyte-derived macrophages. In summary, the present data, demonstrating a LDL-induced up-regulation of the endothelin system in coronary smooth muscle cells and in monocyte-derived macrophages, provide further support for a pathophysiological role of endothelin in coronary atherosclerosis and suggest that ET-1 might be involved in mediating the atherogenic effects of LDL.

Cells, Cultured↗
PubMed1976

High volume screening procedures for hypobetalipoproteinemic activity in rats.

We describe high volume screening tests for hypobetalipoproteinemic agents in which compounds are administered orally to cholesterol-cholic acid fed (hypercholesterolemic( or normally fed weanling rats for 4 days. In these tests total serum cholesterol levels and heparin precipitating lipoproteins (HPL) are determined by automated analyses interfaced with a computer which eliminates all manual data reduction and provides necessary reports. The hypercholesterolemic rat test detects compounds which specifically reduce HPL (beta and pre beta lipoproteins) causing a decrease in the HPL: cholesterol ratio. Such activity is called hypobetalipoproteinemia. This activity is exhibited by bicyclo (2.2.2)-octyloxyaniline (U-26328) but not by any of the familiar hypocholesterolemic agents including clofibrats, lifibrats, nicotinic acid, probucol, triparanol, lentysine, D-throxine or the estrogens estrone and diethylstilbestrol.

Analog-Digital Conversion↗
PubMed2004

Regulation of mitochondrial transcription factor A expression by high glucose.

Mitochondrial transcription factor A (Tfam, previously mtTFA) is a key regulator of mitochondrial DNA (mtDNA) transcription and replication. We have reported that overexpression of nuclear respiratory factor-1 (NRF-1) and high concentration (50 mM) of glucose increased the promoter activity of the rat Tfam in L6 rat skeletal muscle cells. In this study, we investigated the mechanism of high glucose-induced Tfam transactivation. The addition of 50 mM glucose for 24 h increased Tfam promoter activity up to twofold. The glucose-induced Tfam expression was dose-dependent and cell-type specific. Glucose increased the Tfam promoter-driven transactivity in L6 (skeletal muscle), HIT (pancreatic beta-cell), and CHO (ovary) cells, but not in HepG2 (hepatoma), HeLa, and CV1 (kidney) cells. Among various monosaccharides, only glucose and fructose increased the Tfam promoter activity. Oxidative stress might not be involved in glucose-induced Tfam expression since treatment with antioxidants such as vitamin C, vitamin E, probucol, or alpha-lipoic acid did not suppress the induction. None of the inhibitors of protein kinase C, MAP kinase, and PI3 kinase altered the glucose-induced Tfam promoter activity, suggesting that general phosphorylation is involved in its signaling. However, a dominant negative mutant of NRF-1, in which 200 amino acids of C-terminus were truncated, completely suppressed the glucose-induced Tfam induction. It was concluded that high glucose-induced Tfam transcription in L6 cells might be mediated by NRF-1.

Animals↗
PubMed1993

Influences of lipid-modifying agents on hemostasis.

Drugs affecting lipid metabolism may influence, to a variable extent, the hemostatic system, that is, platelet activation, fibrinogen, and fibrinolysis. These effects may or may not be linked to the activity of these compounds on the lipid/lipoprotein profile. For this reason it may be important to consider the effects of hypolipidemic drugs on the different aspects of hemostasis, because this may allow a better understanding of their clinical use, as well as, eventually, a more proper selection in individual patients. Among the major lipid-lowering agents, fibric acids belong to a multifaceted series of abnormal fatty acids known to interact with a liver nuclear receptor, in turn activating fatty acid catabolism. A similar activity may be exerted by n-3 fatty acids from fish, as well as by other chemically related or unrelated compounds. Among fibric acids all but gemfibrozil can reduce fibrinogen levels; this last drug can, however, apparently activate fibrinolysis. Among the selective cholesterol-lowering medications, both resins and HMG CoA reductase inhibitors may reduce, in some patients, over prolonged periods of treatment, platelet sensitivity to major aggregants. This effect may be seen best with non-liver-selective agents (e.g., simvastatin), although recent data cast doubt on its constancy. A direct comparative evaluation of different HMG CoA reductase inhibitors on platelet aggregability has never been carried out. These last drugs may also reduce the circulating levels of the tissue factor pathway inhibitor (TFPI), transported by LDL in plasma, which is a potentially negative effect. A lipid-lowering molecule with antioxidant activity, for example, probucol, may also possibly play a role in controlling platelet activation.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Trials as Topic↗
PubMed1991

Lipid changes in the nephrotic syndrome: new insights into pathomechanisms and treatment.

The abnormalities of lipid metabolism in nephrotic syndrome consist in an increase in total and low-density lipoprotein (LDL) cholesterol, apolipoproteins B (ApoB), C-II and C-III, associated in patients with heavier or marked hypoalbuminemia with an increase in triglycerides and very low-density lipoprotein (VLDL) cholesterol, while the high-density lipoproteins (HDL) are distributed abnormally (increased HDL3 fraction and decreased HDL2 fraction) and the Apo A-I to Apo B ratio is reduced. Both increased hepatic lipoprotein synthesis and reduced removal capacity contribute to this hyperlipidemia. Proteinuria may lead to the lipoprotein abnormalities through stimulation of VLDL synthesis by the liver induced by hypoalbuminemia, although it has been more recently suggested that urinary protein loss is associated with the urinary loss of some important cofactor for the regulation of lipid synthesis or catabolism. Treatment of lipid abnormalities in patients with long-lasting heavy proteinuria is mandatory, because they may cause or contribute to accelerated atherosclerosis, but also because they appear to accelerate progression of renal disease by favouring mesangial sclerosis. Four groups of lipid-lowering drugs have been tested: 1) bile acid-binding resins; 2) fibric acid; 3) probucol; 4) inhibitors of HMG CoA reductase. The drugs of the last group appear to be effective and safe in short-term experiments, but long-term studies are necessary to confirm their validity. A dietary approach, consisting in a strictly vegetarian soy diet, very rich in poly- and monounsaturates fatty acids, has been recently tested by the author, with very promising results.

Arteriosclerosis↗
PubMed1994

Comparative toxicity of oxidatively modified low-density lipoprotein and lysophosphatidylcholine in cultured vascular endothelial cells.

Oxidative modification of low-density lipoprotein (LDL) may play an important role in the initiation and progression of atherosclerosis. We previously showed that the cytotoxicity of oxidized LDL (oxLDL) depended on the level of lipid hydroperoxides. Meanwhile, it has been shown that during LDL oxidation, a significant part of the LDL phosphatidylcholine (PC) is degraded to lysophosphatidylcholine (LPC) by an intrinsic phospholipase A2-like activity, and that LPC is toxic to various cells. In the present study, we compared the toxicity of oxLDL with that of LPC in cultured bovine aortic endothelial cells. Cytotoxicity induced by LPC, assessed by the release of lactate dehydrogenase (LDH), reached a plateau within 1 h. LDH release induced by oxLDL occurred much later, at about 3 h, and increased linearly until nearly all the LDH was released at 10 h. The addition of deferoxamine, a Fe3+ chelator, to the reaction medium prevented the toxic effects of oxLDL, but not of LPC. Native LDL and oxLDL inhibited the toxicity of LPC, while native LDL promoted the toxicity of oxLDL. Albumin inhibited the toxicity of LPC but not of oxLDL. Preincubation of endothelial cells with an antioxidant, probucol, protected against oxLDL toxicity, but not against LPC toxicity. These results suggest that lipid hydroperoxides associated with the oxLDL particle, not LPC, constitute the toxic moiety of oxLDL. These substances may generate lipid peroxyl and alkoxyl radicals in the presence of ionic iron, probably from intracellular iron stores in endothelial cells, and produce cytotoxicity.

Animals↗
PubMedDate not supplied

Oxidative stress and neurodegenerative disorders.

Oxidative insults, whether over-excitation, excessive release of glutamate or ATP caused by stroke, ischemia or inflammation, exposure to ionizing radiation, heavy-metal ions or oxidized lipoproteins may initiate various signaling cascades leading to apoptotic cell death and neurodegenerative disorders. Among the various reactive oxygen species (ROS) generated in the living organism, hydroxyl and peroxynitrite are the most potent and can damage proteins, lipids and nucleic acids. It appears that some natural antioxidants (tocopherol, ascorbic acid and glutathione) and defense enzyme systems (superoxide dismutase, catalase and glutathione peroxidase) may provide some protection against oxidative damage. Recent findings indicate several polyphenols and antioxidant drugs (probucol, seligilline) are effective in protecting the cells from ROS attack. Further development of these antioxidant molecules may be of value in preventing the development of neurodegenerative diseases.

Animals↗
PubMed1995

Antioxidant activity of thiocholesterol on copper-induced oxidation of low-density lipoprotein.

The effect of thiocholesterol (SH-Chol) on the copper-induced in vitro oxidation of low-density lipoprotein (LDL; 1.019 < d < 1.063) was investigated. Among the antioxidants tested, including cysteine, glutathione, 2-mercaptoethanol, dithiothreitol, probucol, thiopalmitic acid, and SH-Chol, SH-Chol was the most effective antioxidant in copper-induced LDL oxidation. Also, SH-Chol completely inhibited the formation of oxysterols, i.e., 7-hydroxycholesterol and 7-ketocholesterol, in LDL particles and reduced 1,1-diphenyl-2-picrylhydrazyl used as stable free-radical model. Moreover, SH-Chol suppressed the degradation of endogenous alpha-tocopherol in LDL particles. These findings indicate that SH-Chol acts as antioxidant in the oxidative damage of LDL in vitro and as a free-radical scavenger in lipid peroxidation.

Antioxidants↗
PubMed1988

Induction of long-lasting hypercholesterolemia in the rat fed a cystine-enriched diet.

The influence of dietary excess (5%) of L-cystine on rat plasma lipoproteins was examined. After only one week of cystine feeding, an increase in the plasma cholesterol level and a decrease in triglyceride levels were observed. The increase in cholesterol level became greater when the duration of cystine-enriched diet increased until eight weeks (+131% after eight weeks), but no further increase occurred between 8 and 20 weeks. This change was essentially due to the progressive increase in cholesterol levels in high density lipoproteins (HDL) and in lipoproteins isolated between 1.040 and 1.063 g/ml, i.e., certain low density lipoproteins (LDL2), and containing mainly apoE-rich lipoproteins (HDL1). The decrease in plasma triglycerides resulted from that of chylomicrons and very low density lipoproteins (VLDL). The effects observed after four or eight weeks of cystine feeding were maintained for eight weeks after replacing the cystine diet by the standard diet. Ingestion of the standard diet containing either cholestyramine (2%) or probucol (0.25%) following eight weeks of cystine feeding significantly decreased plasma cholesterol levels. It is concluded that cystine-fed rats are a useful tool of investigation for understanding mechanisms leading to increased plasma cholesterol level and for hypocholesterolemic drug trials.

Animals↗
PubMed2000

Dopamine induces cell death, lipid peroxidation and DNA base damage in a catecholaminergic cell line derived from the central nervous system.

Dopamine can be autoxidized to superoxides and quinones. Superoxides can form hydroxyl radicals that are highly reactive with lipids, proteins and DNA leading to neuronal damage and cell death. We used a clonal catecholaminergic cell line (CATH.a) derived from the central nervous system to evaluate the effects of dopamine on cell death, lipid peroxidation and DNA base damage. Dopamine produces cell death in CATH.a cells and this is associated with an increase in annexin binding, which is an early indicator of apoptosis. Incubation of CATH.a cells with deferoximine, an iron chealator, partially antagonizes dopamine-induced cell death. In CATH.a cells, dopamine produces an increase in both lipid peroxidation, as measured by cis-parinaric acid fluorescence, and DNA oxidative base damage, as measured by 8-hydroxy-2'-deoxyguanosine formation. Cell death was inhibited 84-92% by the hydrophilic antioxidants, dithiothreitol, L-cysteine, and N-acetylcysteine. The lipophilic vitamins, retinol and vitamin E and the vitamin E analog, Trolox, inhibited dopamine-induced cell death by 18-33%. The lipophilic antioxidants probucol, propyl glycol and butylated hydroxyanisone had no inhibitory effect on dopamine-induced cell death. These data suggest that damage to DNA and lipids may be partially responsible for dopamine-induced cell death in CATH.a cells.

Journal Article↗
PubMedDate not supplied

Adverse effects of hypolipidaemic drugs.

Cholestyramine, colestipol, clofibrate, gemfibrozil, nicotinic acid (niacin), probucol, neomycin, and dextrothyroxine are the most commonly used drugs in the treatment of hyperlipoproteinaemic disorders. While adverse reaction data are available for all of them, definitive data regarding the frequency and severity of potential adverse effects from well-controlled trials using large numbers of patients (greater than 1000) are available only for cholestyramine, clofibrate, nicotinic acid and dextrothyroxine. In adult patients treated with cholestyramine, gastrointestinal complaints, especially constipation, abdominal pain and unpalatability are most frequently observed. Continued administration along with dietary manipulation (e.g. addition of dietary fibre) and/or stool softeners results in diminished complaints during long term therapy. Large doses of cholestyramine (greater than 32 g/day) may be associated with malabsorption of fat-soluble vitamins. Most significantly, osteomalacia and, on rare occasions, haemorrhagic diathesis are reported with cholestyramine impairment of vitamin D and vitamin K absorption, respectively. Paediatric patients have been reported to experience hyperchloraemic metabolic acidosis or gastrointestinal obstruction. Concurrent administration of acidic drugs may result in their reduced bioavailability. Serious adverse reactions to clofibrate will probably limit its role in the future. Of particular concern are ventricular arrhythmias, induction of cholelithiasis and cholecystitis, and the potential for promoting gastrointestinal malignancy which far outweigh the reported benefits in preventing new or recurrent myocardial infarction, cardiovascular death and overall death. Patients with renal disease are particularly prone to myositis, secondary to alterations in protein binding and impaired renal excretion of clofibrate. Drug interactions with coumarin anticoagulants and sulphonylurea compounds may produce bleeding episodes and hypoglycaemia, respectively. Nicotinic acid produces frequent adverse effects, but they are usually not serious, tend to decrease with time, and can be managed easily. Dermal and gastrointestinal reactions are most common. Truncal and facial flushing are reported in 90 to 100% of treated patients in large clinical trials. Significant elevations of liver enzymes, serum glucose, and serum uric acid are occasionally seen with nicotinic acid therapy. Liver enzyme elevations are more common in patients given large dosage increases over short periods of time, and in patients treated with sustained release formulations.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed2004

3,4,5,6-Tetrahydroxyxanthone prevents vascular endothelial cell apoptosis induced by high glucose.

Apoptosis of endothelial cells may be an important risk factor contributing to the incidence of vascular complications in diabetes. In the present study, we tested the effect of 3,4,5,6-tetrahydroxyxanthone, a synthetic xanthone derivative, on apoptosis induced in human umbilical vein endothelial cells (HUVEC) by a high glucose concentration. Cell apoptosis was detected using DNA ladder formation and flow cytometric techniques. The expression of Bcl-2 protein was analysed using flow cytometric techniques. Lactate dehydrogenase (LDH) activity and malonyldialdehyde (MDA) content in the medium were measured. Cell viability was assayed by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) method. Exposure of HUVEC to a high glucose concentration (30 mM) for 48 h markedly increased LDH release and MDA content in the medium and induced apoptosis and Bcl-2 protein expression in HUVEC. Pretreatment with 3,4,5,6-tetrahydroxyxanthone (1, 3 or 10 microM) or probucol (10 microM) significantly decreased the level of LDH and MDA in the medium, reduced apoptosis and increased the expression of Bcl-2 protein in HUVEC. These results suggest that 3,4,5,6-tetrahydroxyxanthone inhibits high-glucose-induced endothelial cell apoptosis by increasing Bcl-2 protein expression in HUVEC.

Apoptosis↗