PMID: 

Thorax. 2015 Jul ;70(7):617-24. Epub 2015 Apr 22. PMID: 25903964

Abstract Title: 

Vitamin D deficiency contributes directly to the acute respiratory distress syndrome (ARDS).

Abstract: 

RATIONALE: Vitamin D deficiency has been implicated as a pathogenic factor in sepsis and intensive therapy unit mortality but has not been assessed as a risk factor for acute respiratory distress syndrome (ARDS). Causality of these associations has never been demonstrated.OBJECTIVES: To determine if ARDS is associated with vitamin D deficiency in a clinical setting and to determine if vitamin D deficiency in experimental models of ARDS influences its severity.METHODS: Human, murine and in vitro primary alveolar epithelial cell work were included in this study.FINDINGS: Vitamin D deficiency (plasma 25(OH)D levels600 genes. In a clinical setting, pharmacological repletion of vitamin D prior to oesophagectomy reduced the observed changes of in vivo measurements of alveolar capillary damage seen in deficient patients.CONCLUSIONS: Vitamin D deficiency is common in people who develop ARDS. This deficiency of vitamin D appears to contribute to the development of the condition, and approaches to correct vitamin D deficiency in patients at risk of ARDS should be developed.TRIAL REGISTRATION: UKCRN ID 11994.

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PMID: 

Mol Med Rep. 2017 Nov ;16(5):7432-7438. Epub 2017 Sep 20. PMID: 28944831

Abstract Title: 

Vitamin D alleviates lipopolysaccharide‑induced acute lung injury via regulation of the renin‑angiotensin system.

Abstract: 

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the clinical manifestations of severe lung damage and respiratory failure. ALI and ARDS result are associated with high mortality in patients. At present, no effective treatments for ALI and ARDS exist. It is established that vitamin D exhibits anti‑inflammatory effects, however, the specific effect of vitamin D on ALI remains largely unknown. The aim of the present study was to investigate whether, and by which mechanism, vitamin D alleviates lipopolysaccharide (LPS)‑induced ALI. The results demonstrated that a vitamin D agonist, calcitriol, exhibited a beneficial effect on LPS‑induced ALI in rats; calcitriol pretreatment significantly improved LPS‑induced lung permeability, as determined using Evans blue dye. Results from reverse transcription‑quantitative polymerase chain reaction, western blotting and ELISA analysis demonstrated that calcitriol also modulated the expression of members of the renin‑angiotensin system (RAS), including angiotensin (Ang) I‑converting enzymes (ACE and ACE2), renin and Ang II, which indicates that calcitriol may exert protective effects on LPS‑induced lung injury, at least partially,by regulating the balance between the expression of members of the RAS. The results of the present study may provide novel targets for the future treatment of ALI.

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PMID: 

Acta Med Indones. 2019 Oct ;51(4):311-317. PMID: 32041914

Abstract Title: 

Effect of Oral N-Acetylcysteine Supplementation on the Immunity System in Patients with Acute Myocardial Infarction.

Abstract: 

BACKGROUND: inflammation, oxidative stress, and fibrosis play important roles after an acute myocardial infarction (AMI) event. The most studied inflammatory biomarker in cardiovascular disease is C-reactive protein (CRP). It has been demonstrated that myeloperoxidase (MPO) and Galectin-3 (Gal-3) have some essential roles on immune system when an AMI event occurs. We aimed to determine the effect of oral N-acetylcysteine (NAC) supplementation at the dose of 600 mg 3 times daily for 3 consecutive days on the immune system of AMI patients.METHODS: our randomized single-blinded experimental study using pre- and post-treatment evaluations was performed at Dr. Moewardi Hospital, Indonesia, from May to August 2018. Thirty-two patients with AMI and ST segment elevation (STEMI) who received fibrinolytic therapy were included. There were 17 patients received standard therapy plus 600 mg oral NAC supplementation every 8 h for 3 days and 15 patients received standard therapy, which served as the control group. High-sensitivity C-reactive protein (HsCRP), MPO, and Gal-3 levels of both groups were evaluated at admission and after 72 h receiving treatment.RESULTS: HsCRP, MPO, and Gal-3 levels between NAC and control groups at admission were not significantly different; while intergroup differences after 72 h of NAC supplementation were significant (p values of HsCRP, MPO, and Gal-3 levels were 0.0001, 0.001, and 0.017, respectively). Furthermore, in the NAC group, HsCRP, MPO, and Gal-3 levels at 72 h after treatment were significantly different from the corresponding levels at admission (p values: 0.0001, 0.0001, and 0.0001, respectively); the control group did not show these differences. There were also significant intergroup differences between the NAC and control groups regarding HsCRP, MPO, and Gal-3 levels (p values: 0.011, 0.022, and 0.014, respectively).CONCLUSION: oral supplementation of 600 mg NAC every 8 h for 72 h can reduce HsCRP, MPO, and Gal-3 levels in AMI patients receiving fibrinolytic therapy. Results of our study will provide more options for supplementation therapy to improve management of IMA patients.

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PMID: 

J Appl Toxicol. 1997 Sep-Oct;17(5):289-95. PMID: 9339741

Abstract Title: 

Vitamin C supplementation on hepatic oxidative stress induced by cigarette smoke.

Abstract: 

A study has been conducted to investigate whether the oxidative damage produced in the liver of rats exposed to cigarette smoke can be effectively combatted with vitamin C, one of the antioxidant vitamins. We assessed the liver antioxidants (vitamins E, C and A), scavenging enzymes and lipid peroxide products of rats exposed to cigarette smoke and simultaneously given vitamin C (200 mg 100 g[-1] body wt.) for 90 days. Malondialdehyde (MDA), conjugated dienes, hydroperoxides and free fatty acids (FFA) were significantly increased in liver of smoke-exposed groups. The activity of superoxide dismutase and catalase and vitamin E and C contents were significantly lower than controls. But vitamin A, glutathione (GSH) content and glutathione peroxidase (GSH Pxase) activity were enhanced. Vitamin C supplementation to smoke-exposed rats showed increased resistance to lipid peroxidation and increased activity of scavenging enzymes. The GSH content, vitamin C and FFA were brought to normal levels. Thus, this study seems to suggest that an intake of a mega dose of vitamin C can protect the liver from oxidant damage caused by cigarette smoke.

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PMID: 

Indian J Physiol Pharmacol. 2000 Oct ;44(4):401-10. PMID: 11214494

Abstract Title: 

Effects of exogenous vitamin C on ethanol toxicity in rats.

Abstract: 

The effect of a mega dose of ascorbic acid (200 mg/100 g body wt.) on alcohol-induced toxicity in rats was evaluated. In rats administered alcohol and ascorbic acid, malondialdehyde (MDA), hydroperoxide and conjugated dienes decreased in comparison with that given alcohol alone. The reduced activities of scavenging enzymes, e.g. superoxide dismutase (SOD) and catalase, in ethanol-administered rats were also enhanced by the co-administration of ascorbic acid and ethanol. Co-administration of ethanol and ascorbic acid reduced phospholipids and MDA levels of the erythrocyte membrane in comparison with that of the ethanol fed rats. The reduction in the activities of glutamic oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), gamaglutamyl transpeptidase (GGT) and the decrease in triglycerides levels also clearly showed the protective action of ascorbic acid in reducing ethanol induced toxicity.

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PMID: 

Med J Aust. 2001 Oct 1 ;175(7):359-62. PMID: 11700812

Abstract Title: 

Mega-dose vitamin C in treatment of the common cold: a randomised controlled trial.

Abstract: 

OBJECTIVE: To determine the effect of large doses of vitamin C in the treatment of the common cold.STUDY DESIGN: Double-blind, randomised clinical trial with four intervention arms: vitamin C at daily doses of 0.03g ("placebo"), 1 g, 3g, or 3g with additives ("Bio-C") taken at onset of a cold and for the following two days.PARTICIPANTS AND SETTING: 400 healthy volunteers were recruited from staff and students of the Australian National University, Canberra, ACT, between May 1998 and November 1999. The trial continued for 18 months.INTERVENTIONS: Participants were instructed to commence medication when they had experienced early symptoms of a cold for four hours, and to record daily their symptoms, severity, doctor visits and use of other medications.MAIN OUTCOME MEASURES: Duration of symptoms and cold episodes; cumulative symptom severity scores after 7, 14 and 28 days; doctor visits; and whether participants guessed which medication they were taking.RESULTS: 149 participants returned records for 184 cold episodes. No significant differences were observed in any measure of cold duration or severity between the four medication groups. Although differences were not significant, the placebo group had the shortest duration of nasal, systemic and overall symptoms, and the lowest mean severity score at 14 days, and the second lowest at 7 and 28 days.CONCLUSIONS: Doses of vitamin C in excess of 1 g daily taken shortly after onset of a cold did not reduce the duration or severity of cold symptoms in healthy adult volunteers when compared with a vitamin C dose less than the minimum recommended daily intake.

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PMID: 

Anat Cell Biol. 2010 Dec ;43(4):294-302. Epub 2010 Dec 31. PMID: 21267403

Abstract Title: 

Mega-dose vitamin C attenuated lung inflammation in mouse asthma model.

Abstract: 

Asthma is a Th2-dependent disease mediated by IgE and Th2 cytokines, and asthmatic patients suffer from oxidative stresses from abnormal airway inflammation. Vitamin C is a micro-nutrient functioning as an antioxidant. When administered at a mega-dose, vitamin C has been reported to shift immune responses toward Th1. Thus, we tried to determine whether vitamin C exerted beneficial effects in asthma animal model. Asthma was induced in mice by sensitizing and challenging with ovalbumin. At the time of challenge, 3~5 mg of vitamin C was administered and the effects were evaluated. Vitamin C did not modulate Th1/Th2 balance in asthma model. However, it decreased airway hyperreactivity to methacholine, decreased inflammatory cell numbers in brochoalveolar lavage fluid, and moderate reduction of perivascular and peribronchiolar inflammatory cell infiltration. These results suggest that vitamin C administered at the time of antigen challenge exerted anti-inflammatory effects. Further studies based on chronic asthma model are needed to evaluate a long-term effect of vitamin C in asthma. In conclusion, even though vitamin C did not show any Th1/Th2 shifting effects in this experiment, it still exerted moderate anti-inflammatory effects. Considering other beneficial effects and inexpensiveness of vitamin C, mega-dose usage of vitamin C could be a potential supplementary modality for the management of asthma.

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PMID: 

Immunol Lett. 2005 Apr 15 ;98(1):63-72. PMID: 15790510

Abstract Title: 

Mega-dose Vitamin C modulates T cell functions in Balb/c mice only when administered during T cell activation.

Abstract: 

Previously we reported that a mega-dose of Vitamin C enhanced the initial stage of delayed-type hypersensitivity reaction in Balb/c mice. In this study its effects were further evaluated as follows. Mice were administered Vitamin C intraperitoneally at 0.625 mg/day or at 5mg/day for variable days before, during, or after being sensitized with DNFB. T cells were isolated in each group and examined. When stimulated antigen-specifically or non-specifically in vitro, mice showed elevated thymidine uptake and a shift of cytokine secretion profiles toward Th1, i.e., elevated levels IL-2, TNF-alpha, and IFN-gamma, and lowered level of the Th2 cytokine IL-4, only when Vitamin C was administered during sensitization. T cells from those mice administered Vitamin C before sensitization or after challenge showed the same T cell properties as those from PBS-treated mice. Mice were also given 0.625 mg/day of Vitamin C during primary and/or secondary immunizations with KLH and secondary specific antibody titers in sera were measured. The total specific antibody titer was lowered in Vitamin C-treated animals whenever treatments were administered, and this was entirely attributed to decreased levels of IgG1 and IgE antibodies. Based on these results, we suggest that an exogenously administered mega-dose of Vitamin C shifts immunity in Balb/c mouse toward Th1 and that these affects occur only when Vitamin C is administered during T cell activation.

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PMID: 

Z Naturforsch C J Biosci. 2004 Jul-Aug;59(7-8):468-76. PMID: 15813363

Abstract Title: 

Antioxidant and immunomodulatory constituents of henna leaves.

Abstract: 

The immunomodulatory bioassay-guided fractionation of the methanolic extract of henna (Lawsonia inermis L.; syn. Lawsonia alba L.) leaves resulted in the isolation of seven compounds; three have been isolated for the first time from the genus, namely p-coumaric acid, 2-methoxy-3-methyl-1,4-naphthoquinone and apiin, along with the previously isolated compounds: lawsone, apigenin, luteolin, and cosmosiin. Structural elucidation of the isolated compounds was based upon their physical, chemical as well as spectroscopic characters. Their immuomodulatory profile was studied using an in vitro immunoassay, the lymphocyte transformation assay. The ABTS [2,2'-azino-bis (3-ethyl benzthiazoline-6-sulfonic acid)], free radical scavenging assay depicted that all isolated compounds exhibited antioxidant activity comparable to that of ascorbic acid.

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PMID: 

Free Radic Res. 2005 Jun ;39(6):659-66. PMID: 16036344

Abstract Title: 

Antioxidant supplementation reduces inter-individual variation in markers of oxidative damage.

Abstract: 

The aim of this study was to examine the effect of antioxidant supplementation on oxidative damage and chromosome stability in middle-aged men, smokers and non-smokers. A total of 124 men aged 48+/-6 years from Bratislava and from the rural population near Bratislava were investigated; 64 men (22 smokers and 42 non-smokers) were supplemented for 12 weeks with antioxidants, while 60 (25 smokers and 35 non-smokers) were given placebo. The daily antioxidant supplementation consisted of vitamin C (100 mg), vitamin E (100 mg), ss-carotene (6 mg), and selenium (50 microg). Samples of blood were taken on two occasions: At the beginning and at the end of the supplementation trial. Concentrations of dietary antioxidants, ferric reducing ability, malondialdehyde as an indicator of lipid peroxidation in plasma, micronuclei and chromosome aberrations in lymphocytes were measured. Antioxidant supplementation significantly increased the levels of vitamin C, ss-carotene, a-tocopherol and selenium in plasma. The overall antioxidant status of plasma measured as ferric reducing ability of plasma (FRAP) increased significantly (p

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