PMID: 

Eur J Nutr. 2001 Apr ;40(2):56-65. PMID: 11518200

Abstract Title: 

Short-term fish oil supplementation improved innate immunity, but increased ex vivo oxidation of LDL in man–a pilot study.

Abstract: 

BACKGROUND: Fish and fish oils are rich in the two long-chain polyunsaturated fatty acids (LCPUFAs) eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3). The n-3 LCPUFAs have been reported to have beneficial effects on cardiovascular functions, but their role in relation to immune functions is still controversial.AIM OF THE STUDY: The objectives of this study were to determine the effects of supplementation with fish oil on immune cell functions in human subjects. We have also assessed the effects on plasma lipids, antioxidant status and susceptibility of low-density lipoproteins (LDL) to oxidative stress. The antioxidant status was determined by measuring plasma vitamin C, tocopherols and carotenoids in plasma and LDL, and superoxide dismutase (SOD) in red blood cells.DESIGN: For 30 days, 10 volunteers ingested 25 g/d of either fish oil, providing n-3 LCPUFAs (7.5 g), or high-oleic sunflower oil, providing monounsaturated fatty acids mainly as oleic acid (22 g). The oils contained similar profiles of tocopherols. At day 0 and day 30, blood samples were drawn by venipuncture for plasma lipid and antioxidant analyses and lipoprotein isolation, and for isolation and functional tests of mononuclear cells and granulocytes. Fatty acid profiles of im mune cells and LDL were also determined.RESULTS: Fish oil supplementation resulted in an accumulation of n-3 LCPUFAs (EPA, DHA) in LDL and immune cells. The phagocytic activity, a measure of immune cell activity, was increased in both groups. Whereas the plasma and LDL antioxidant status do not appear to be affected by fish oil supplementation, an increased susceptibility of LDL to oxidation was observed in these healthy volunteers.CONCLUSIONS: The optimal amounts of n-3 fatty acids required to modulate immune functions remain to be established. In addition, adequate levels of antioxidant protection need to be provided during fish oil supplementation.

read more

PMID: 

Mutat Res. 2001 Nov 15 ;498(1-2):89-98. PMID: 11673074

Abstract Title: 

Anticlastogenic effect of Vitamin C on cisplatin induced chromosome aberrations in human lymphocyte cultures.

Abstract: 

Vitamin C (ascorbic acid) is an antioxidant that can scavenge free radicals and protect cellular macromolecules, including DNA, from oxidative damage induced by different agents. The protective effect of Vitamin C on cisplatin induced chromosome aberrations has been determined in the human peripheral lymphocyte chromosome aberration test in vitro. The results of treatments with Vitamin C indicated that it statistically significantly decreases the number of chromosome aberrations and number of metaphases with aberrations induced with cisplatin, but it can not completely protect cells from damage. The test concentrations of Vitamin C (10 and 100 microg/ml) had a limited antimutagen effect on cisplatin (0.5 microg/ml), which can cause genetic damage through free radical mechanisms. The antimutagen effect included the anticlastogenic effect of Vitamin C and its ability to decrease the number of aneuploid mitoses. Vitamin C showed the most efficient anticlastogenic effect during simultaneous treatment with cisplatin. Also, Vitamin C reduced cell toxicity of cisplatin during simultaneous treatment.

read more

PMID: 

Free Radic Res. 2001 Jul ;35(1):73-84. PMID: 11697119

Abstract Title: 

Ascorbic acid and N-acetylcysteine improve in vitro the function of lymphocytes from mice with endotoxin-induced oxidative stress.

Abstract: 

Oxidative stress associated with reactive oxygen species (ROS) and cytokines produced by immune cells, which is involved in septic shock caused by endotoxin, can be controlled to a certain degree by antioxidants with free radical scavenging action. N-acetylcysteine (NAC) and ascorbic acid (AA) are ROS scavengers that improve the immune response, and modulate macrophage function in mice with endotoxin-caused oxidative stress. Therefore, we have investigated the in vitro effects of these antioxidants on the functions of lymphocytes from BALB/c mice with lethal endotoxic shock caused by intraperitoneal injection of E. coli lipopolysaccharide (LPS) (100 mg/kg). Adherence to tissues and chemotaxis (the earliest two functions of lymphocytes in the immune response), as well as ROS levels and TNF alpha production were determined in the presence or absence of NAC or AA (0.001, 0.01, 0.1, 1 and 2.5 mM) in lymphocytes from peritoneum, axillary nodes, spleen and thymus obtained at several times (2, 4, 12 and 24 hours) after LPS injection. Endotoxic shock decreases the chemotaxis of lymphocytes from all the above localizations and increases their adherence, TNF alpha and ROS production. These changes in lymphocyte function were counteracted by NAC and AA, bringing these functions to values near those of control animals. Our data suggest that lymphocytes are important targets of endotoxins contributing to oxidative stress by septic shock, and that antioxidants can preserve the function of lymphocytes, preventing the homeostatic disturbances caused by endotoxin.

read more

PMID: 

Toxicol In Vitro. 2001 Dec ;15(6):649-54. PMID: 11698165

Abstract Title: 

Role of ascorbic acid on mercuric chloride-induced genotoxicity in human blood cultures.

Abstract: 

Efforts are made to find therapeutic agents capable of minimizing genotoxicity of various natural and man-made compounds. The genotoxicity induced by mercury compounds remains controversial. Therefore we have investigated the genotoxic effect of mercuric chloride (MC; HgCl(2)) at three concentrations (1.052, 5.262 and 10.524 microM) and role of L-ascorbic acid (vitamin C) at a concentration of 9.734 microM on MC-treated short-term human leucocyte cultures. We assessed the proliferative rate index (PRI), sister chromatid exchange (SCE) and chromosomal aberrations (CAS) in control and MC-treated cultures with and without vitamin C supplementation. The results showed that MC has no effect on cell-cycle kinetics, but the frequency of SCE/cell was significantly higher in a dose-dependent manner than control values. HgCl(2) also significantly induced C-anaphases (abnormal mitosis) in blood cultures. These effects were prevented by the addition of vitamin C to MC-treated cultures. The data indicate the mutagenic activity of MC and the protective role of vitamin C on mercury-induced genotoxicity in human blood cultures is probably due to its strong antioxidant and nucleophilic nature.

read more

PMID: 

Cytokine. 2004 Aug 21-Sep 7;27(4-5):101-6. PMID: 15271375

Abstract Title: 

Effects of vitamin C on intracytoplasmic cytokine production in human whole blood monocytes and lymphocytes.

Abstract: 

BACKGROUND: Vitamin C (ascorbic acid) is an essential water-soluble nutrient which primarily exerts its effect on immune homeostasis as physiological antioxidant. However, conflicting data exist regarding the effect of vitamin C on the expression of pro-inflammatory cytokines.METHODS: It was the aim of this study to investigate the impact of vitamin C on intracytoplasmic production of pro-inflammatory cytokines in monocytes and lymphocytes by flow cytometry after human whole blood assay.RESULTS: Vitamin C dose dependently inhibited the LPS-induced number of monocytes producing IL-6 (e.g., 41.0% reduction, p

read more

PMID: 

Zhonghua Yu Fang Yi Xue Za Zhi. 2002 Jan ;36(1):25-9. PMID: 11955344

Abstract Title: 

[The effect of vitamin C in oxidative modification of low-density lipoprotein induced by macrophage and copperion].

Abstract: 

OBJECTIVE: To study the effect of vitamin C on preventing oxidative modification of low density lipoprotein cholesterol (LDL) in vitro.METHODS: Different levels of vitamin C were added to two different systems of lipid peroxidation of LDL induced by either Cu(2+) or macrophage. The level of VC in systems induced by Cu(2+) were 10, 50, 100 and 200 micromol/L respectively and by macrophage were 50, 100, 200 micromol/L respectively. Vitamin E (200 micromol/L) and VC(0) (0 micromol/L) were served as positive and negative control respectively. The content of TBARS, Ox-LDL, fluorescent compounds, electrophoretic mobility of LDL and the lag-phage of oxidation of LDL were measured.RESULTS: In the oxidative systems induced by Cu(2+), the groups with higher levels of VC (100, 200 micromol/L) reduced the levels of TBARS, Ox-LDL at 3, 6, and 9 hour after adding Cu(2+), but low dose groups (10, 50 micromol/L) had no the effects. In the macrophage systems, higher levels of VC (100, 200 micromol/L) significantly reduced levels of fluorescent compounds and TBARS, and also lowered electrophoretic mobility of LDL and increased the lag-phage of oxidation of LDL.CONCLUSION: Vitamin C has dual effect on oxidation of LDL. Low dose treatment enhanced oxidation of LDL, but high doses has anti-oxidative effects on LDL.

read more

PMID: 

Hypertension. 2003 Feb ;41(2):341-6. PMID: 12574105

Abstract Title: 

Antioxidant-rich diet relieves hypertension and reduces renal immune infiltration in spontaneously hypertensive rats.

Abstract: 

Previous studies have demonstrated that oxidative stress contributes to hypertension and treatments with either antioxidant or immunosuppressive/anti-inflammatory agents improve hypertension in spontaneously hypertensive rats (SHR). The present study was performed to determine if the antihypertensive effects of an antioxidant-rich diet are associated with reduction in the renal immune infiltration. Rats were divided into experimental groups (n=5 each) that were followed 7 months after birth, during which they were fed either a regular or antioxidant-enriched (test) diet as follows: SHR-R group=regular diet; SHR-T group=test diet throughout the experiment; SHR-S group=test diet for 4 months switched to regular diet thereafter; WKY group=control rats given regular diet. The SHR-T rats showed a significant reduction in systolic blood pressure (mm Hg): SHR-T=179.6+/-12.9 versus SHR-R=207.5+/-9.6 (P

read more

PMID: 

Blood. 2003 Jul 1 ;102(1):336-43. Epub 2003 Mar 6. PMID: 12623840

Abstract Title: 

Vitamin C inhibits FAS-induced apoptosis in monocytes and U937 cells.

Abstract: 

The FAS receptor-FAS ligand system is a key apoptotic pathway for cells of the immune system. Ligation of the FAS-receptor (CD95) induces apoptosis by activation of pro-caspase-8 followed by downstream events, including an increase in reactive oxygen species (ROS) and the release of proapoptotic factors from the mitochondria, leading to caspase-3 activation. We investigated the role of vitamin C in FAS-mediated apoptosis and found that intracellular accumulation of pharmacologic concentrations of vitamin C inhibited FAS-induced apoptosis in the monocytic U937 cell line and in fresh human monocytes. Cells were loaded with vitamin C by exposure to dehydroascorbic acid (DHA), thereby circumventing in vitro artifacts associated with the poor transport and pro-oxidant effects of ascorbic acid (AA). Vitamin C inhibition of FAS-mediated apoptosis was associated with reduced activity of caspase-3, -8, and -10, as well as diminished levels of ROS and preservation of mitochondrial membrane integrity. Mechanistic studies indicated that the major effect of vitamin C was inhibition of the activation of caspase-8 with no effect on it enzymatic activity. An independent action of high intracellular concentrations of vitamin C on mitochondrial membrane stabilization was also detected. These studies illuminate the nature of redox-dependent signaling in FAS-induced apoptosis of human monocytes and suggest that vitamin C can modulate the immune system by inhibiting FAS-induced monocyte death.

read more

PMID: 

Diabetes Metab Res Rev. 2003 Jan-Feb;19(1):60-8. PMID: 12592645

Abstract Title: 

Ascorbic acid supplementation restores defective leukocyte-endothelial interaction in alloxan-diabetic rats.

Abstract: 

BACKGROUND: Defective leukocyte-endothelial interactions are observed in experimental diabetes and may reduce the capacity to mount an adequate inflammatory response. The present study investigated the effect of ascorbic acid, an inhibitor of free radical and glycated protein formation as well as an aldose reductase inhibitor, on leukocyte-endothelial interaction in alloxan-diabetic rats.METHODS: Rats were rendered diabetic by alloxan injection (40 mg/kg; iv). After 30 days, diabetic and nondiabetic controls were supplemented for 12 days with ascorbic acid (50 or 200 mg/kg/day) or received saline by gavage. The number of rollers, stickers after zymosan-activated plasma (10%) or leukotriene B(4) (1 microM) applied topically, and migrated cells after local injection of carrageenan (100 microg) were determined in the venules of the internal spermatic fascia by intravital microscopy. Erythrocyte velocity and wall shear rate were determined as well. Reactive oxygen species formation by endothelial cells was measured in vivo by the same technique. Immunocytochemistry for ICAM-1 detection on the endothelium of the venules of the internal spermatic fascia was carried out in cross sections of the whole testis of the animals.RESULTS: The reduced number of rollers, stickers and migrated cells, as well as the higher production of reactive oxygen species by endothelial cells in diabetic rats was corrected by ascorbic acid supplementation. The low immunoreactivity for ICAM-1 in the venules of diabetic rats was improved by ascorbic acid supplementation. Ascorbic acid supplementation did not interfere with erythrocyte velocity or wall shear stress. Ascorbic acid administered to control rats did not alter the parameters studied above.CONCLUSION: We conclude that ascorbic acid improves leukocyte-endothelial interaction in diabetic rats at least in part by restoring the expression of ICAM-1 in the venules of diabetic rats.

read more

PMID: 

J Atheroscler Thromb. 2003 ;10(1):7-12. PMID: 12621158

Abstract Title: 

Ascorbic acid augments cytotoxicity induced by oxidized low-density lipoprotein.

Abstract: 

Although ascorbic acid (ASA) is known as a water-soluble antioxidant, we found that it accelerated the cytotoxicity induced by oxidized low-density lipoprotein (OxLDL) in vitro. This suggests that ASA may enhance the oxidation of LDL to augment the atherogenic activities of OxLDL under certain conditions. Thus, this study was designed to investigate the underlying mechanism that ASA enhances OxLDL-induced cytotoxicity. ASA enhanced the cytotoxicity of macrophage cell line (J774) induced by OxLDL in a dose-dependent manner, whose effect was more apparent in high glucose concentration in the medium. The ASA-induced enhancement in cytotoxicity was inhibited by the presence of lipid-soluble antioxidants, such as alpha-tocopherol and probucol, suggesting that the pro-cytotoxic effect by ASA is likely due to its pro-oxidant property. We also investigated the effects of ASA at different time points on the Cu2+-mediated oxidation of LDL. ASA decreased the rate of conjugated dienes formation when added at the early phase of oxidation, whereas it increased when added at the late phase of oxidation. These data suggest that ASA may act as a pro-oxidant under the condition of extensive LDL oxidation. To prevent oxidation stress, ASA would be better used together with lipid-soluble antioxidants for antioxidant therapies.

read more