BACKGROUNDS:Hepatotoxicity due to anti tuberculosis drugs, rifampin and isoniazid, is a major problem in tuberculosis patients. Vitamin C, an antioxidant, and N-acetyl cysteine (NAC), a scavenger of active metabolites, reduce the hepatotoxicity. The aim of present study was to investigate the effect of vitamin C and NAC individually on the antibacterial activity of anti tuberculosis drugs against Mycobacterium tuberculosis and Staphylococcus aureus strains.

METHODS:The MICs of each compound against all strains were determined in 96 wells plate. Rifampin was tested at serial two fold concentrations alone or in combination with NAC or vitamin C.

RESULTS:The MIC of rifampin against different strains of S. aureus was 0.008-0.032 μg/ml. The MIC of rifampin and isoniazid against M. tuberculosis strains were 40 and 0.2 μg/ml, respectively. Vitamin C and NAC had no antibacterial activity against all strains. MIC of rifampin was reduced two fold by combination with vitamin C for all S. aureus strains, while NAC did not affect the antibacterial activity of rifampin. Vitamin C and NAC had remarkable effects on the antibacterial activity of anti-tuberculosis drugs against M. tuberculosis.

CONCLUSIONS:Synergistic effects were observed between rifampin or isoniazid and vitamin C against all tested strains. However, combination therapy of rifampin and isoniazid with NAC was not being effective. This study highlighted the advantages of combination of anti-tuberculosis drugs and vitamin C to eradicate the microbial infections.

Although cisplatin is a potent anticancer drug, it instigates oxidative and pro-inflammatory reactions which poses significant and distressing clinical symptoms in patients including nausea and vomiting which is related to damage of the gastric mucosa. This study investigated the effects of vitamin C and/or L-carnitine on cisplatin-induced gastric mucosa damage in rat. The rats were allocated into groups (n=5): a control group received distilled water and treatment groups received cisplatin (CIP) alone, cisplatin followed by vitamin C, L-carnitine or their combination. Cisplatin treatment caused disruption of the gastric mucosa histoarchitecture and alter the mucus barrier function in the gastric mucosa. Moreover, stomach tissue from the CIP treated group had increased levels of oxidative stress markers, malondialdehyde and H2O2 levels, and decreased activity of the antioxidant enzymes superoxide dismutase, glutathione peroxidase, catalase, glutathione S-transferase and non-antioxidant enzyme, reduced glutathione level. These deleterious events were accompanied by upregulated levels of the pro-inflammatory cytokines, tumor necrosis factor-alpha, interleukin-1beta, and inflammatory infiltration markers, myeloperoxidase and inducible nitric oxide synthase (iNOS). However, administration of both vitamin C and L-carnitine, and not the either of the two showed additive effect in attenuating these toxic effects which were confirm histologically. In conclusion, the combined administration of vitamin C and L-carnitine, but not the single therapy, could prevent the adverse effects of cisplatin on gastric tissues.

This study was aimed to evaluate the combined effect of curcumin with vitamin C supplementation on hyperglycemic and dyslipidemia conditions and endothelial cell dysfunction induced in diabetic rats. Wistar Furth rats were used and divided into four groups: control (single injection of 0.9% sterile saline), STZ (streptozotocin, Sigma, 55 mg/kg.BW, i.v.), STZ-vitC (1 g/l ascorbic acid mixed in drinking water), STZ-cur (daily oral treatment of 300 mg/kg.BW curcumin; Cayman Chemical Co., USA), and STZ-cur+vitC (1 g/l ascorbic acid mixed in drinking water and oral treatment of 300 mg/kg.BW curcumin). On 8th week after STZ-injection, the microcirculation in the iris tissue was observed using intravital fluorescence videomicroscopy, and also leukocyte adhesion in the venule was examined for each group. Blood glucose (BG), lipid profiles, glycosylated hemoglobin (HbA1c) were measured in blood samples collected at the end of each experiment. The contents of liver malondialdehyde (MDA) were also quantified for each group. Feeding curcumin (STZ-cur) could decrease BG, HbA1c, dyslipidemia, and MDA significantly, compared to STZ. In cases of feedings curcumin with vitamin C, these results were more effective in all aspects, including leukocyte adhesion. In conclusion, curcumin might increase the effect of vitamin C in protecting the function of endothelial cells through its anti-oxidant with hypoglycemic and hypolipidemic actions.

Occurrence of influenza pandemics is a worldwide phenomenon and a significant cause of mortality and morbidity throughout the globe. It is due to mutations in the influenza virus genetic material creating antigenic drift of pathogenic viral proteins resulting in emergence of new influenza virus strains. Therefore, the vaccines available for prevention of influenza offer no protection against influenza pandemics caused by new virus strains. Moreover, the existing drugs used to combat influenza may be ineffective to treat influenza pandemics due to the emergence of drug resistance in the pandemic virus strain. Therefore, a working strategy must be developed to combat influenza pandemics. In this review we have addressed this problem and reviewed the published studies on ascorbic acid in the common cold and influenza and laboratory studies on the effect of ascorbic acid on influenza virus. We have also correlated the clinical and laboratory studies and developed a hypothesis to prevent influenza pandemics.

Sulindac has anti-neoplastic properties against colorectal cancers; however, its use as a chemopreventive agent has been limited due to toxicity and efficacy concerns. Combinatorial treatment of colorectal cancers has been attempted to maximize anti-cancer efficacy with minimal side effects by administrating NSAIDs in combination with other inhibitory compounds or drugs such as L-ascorbic acid (vitamin C), which is known to exhibit cytotoxicity towards various cancer cells at high concentrations. In this study, we evaluated a combinatorial strategy utilizing sulindac and vitamin C. The death of HCT116 cells upon combination therapy occurred via a p53-mediated mechanism. The combination therapeutic resistance developed in isogenic p53 null HCT116 cells and siRNA-mediated p53 knockdown HCT116 cells, but the exogenous expression of p53 in p53 null isogenic cells resulted in the induction of cell death. In addition, we investigated an increased level of intracellular ROS (reactive oxygen species), which was preceded by p53 activation. The expression level of PUMA (p53-upregulated modulator of apoptosis), but not Bim, was significantly increased in HCT116 cells in response to the combination treatment. Taken together, our results demonstrate that combination therapy with sulindac and vitamin C could be a novel anti-cancer therapeutic strategy for p53 wild type colon cancers.

The central cholinergic pathways play a prominent role in the learning and memory processes. Acetylcholinesterase is an enzyme that inactivates acetylcholine. The present study was undertaken to estimate the acetylcholinesterase- inhibiting activity of extracts of Glycyrrhiza glabra, Myristica fragrans seeds, and ascorbic acid and compare these values with a standard acetylcholinesterase-inhibiting drug, metrifonate. Aqueous extract of G. glabra (150 mg/kg p.o. for 7 successive days), n-hexane extract of M. fragrans seeds (5 mg/kg p.o. for 3 successive days), ascorbic acid (60 mg/kg i.p. for 3 successive days), and metrifonate (50 mg/kg i.p.) were administered to young male Swiss albino mice. Acetylcholinesterase enzyme was estimated in brains of mice. G. glabra, M. fragrans, ascorbic acid, and metrifonate significantly decreased acetylcholinesterase activity as compared with their respective vehicle-treated control groups. 

BACKGROUND:This study aimed to test the beneficial effect of grape seed extract (GSE) (Vitis vinifera) and Vitamin C in oxidative stress and reperfusion injury induced by cardiopulmonary bypass (CPB) in coronary artery bypass surgery.

PATIENTS AND METHODS:In this randomized trial, 87 patients undergoing elective and isolated coronary bypass surgery included. The patients were randomly assigned into three groups (n = 29 each): (1) Control group with no treatment, (2) GSE group who received the extract 24 h before operation, 100 mg every 6 h, orally, (3) Vitamin C group who received 25 mg/kg Vitamin C through CPB during surgery. Blood samples were taken from coronary sinus at (T1) just before aortic cross clamp; (T2) just before starting controlled aortic root reperfusion; and (T3) 10 min after root reperfusion. Some clinical parameters and biochemical markers were compared among the groups.

RESULTS:There were significant differences in tracheal intubation times, sinus rhythm return, and left ventricular function between treatment groups compared with control (P<0.05). Total antioxidant capacity was higher (P<0.05) in both grape seed and Vitamin C groups at T2 and T3 times. In reperfusion period, malondialdehyde level was increased in control group; however, it was significantly lower for the grape seed group (P = 0.04). The differences in the mean levels of superoxide dismutase and glutathione peroxidase among the three groups were not significant (P>0.05 in all cases).

CONCLUSIONS:In our patients, GSE and Vitamin C had antioxidative effects and reduced deleterious effects of CPB during coronary artery bypass grafting surgery.

BACKGROUND:Intra-articular injections of local anesthetics are commonly used to enhance post-operative analgesia following orthopedic surgery as arthroscopic surgeries. Nevertheless, recent reports of severe complications due to the use of intra-articular local anesthetic have raised concerns.

OBJECTIVES:The study aims to assess use of vitamin C in reducing adverse effects of the most commonly employed anesthetics - ropivacaine, bupivacaine and lidocaine - on human chondrocytes.

METHODS:The chondrocyte viability following exposure to 0.5% bupivacaine or 0.75% ropivacaine or 1.0% lidocaine and/or vitamin C at doses 125, 250 and 500μM was determined by LIVE/DEAD assay and annexin V staining. Expression levels of caspases 3 and 9 were assessed using antibodies by Western blotting. Flow cytometry was performed to analyze the generation of reactive oxygen species.

RESULTS:On exposure to the local anesthetics, chondrotoxicity was found in the order ropivacaine<bupivacaine

CONCLUSIONS:Vitamin C was observed to effectively protect chondrocytes against the toxic insult of local anesthetics ropivacaine, bupivacaine and lidocaine.

Objective:Vitamin D and C levels have inverse relation with the metabolic syndrome components and they are used as antioxidant supplements during enduring metabolic activities. In the present study, we hypothesized that the intake of vitamin D and/or C with endurance physical activity might reduce the risk of metabolic syndrome.

Methods:A randomized control study recruited 180 participants of both genders, aged between 30 and 50 years. The participants were assigned into six groups receiving different doses of vitamin D or vitamin C with or without physical activities. Data were collected over a period of 3 months, and the results were analyzed using SPSS version 20.

Results:Variations in the effect of the supplements on various body variables including: Fasting plasma glucose, total cholesterol, low-density lipoprotein cholesterol and blood pressure, showed that vitamin D has more influence compared to vitamin C. However, vitamin D and C supplements do not have any effect on weight when consumers are undergoing endurance physical exercise. But vitamin C consumer group has more effect in waist circumference, triglyceride, and high-density lipoprotein, as compared to vitamin D consumer group.

Conclusion:We conclude that, consumption of vitamin D or vitamin C supplements may improves the life of metabolic syndrome patients. However, the combination of physical activities and vitamin supplements maximize the effect, and this combination should be recommended.WHO-ICTRP IRCT20161110030823N2. Registered 01 February 2018. https://apps.who.int/trialsearch/Trial2.aspx?TrialID=IRCT20161110030823N2.

BACKGROUND:Chemopreventive effects and the underlying mechanisms of blueberry (Vaccinium spp.) are not clearly understood in human. We hypothesized blueberry would work via antioxidative and epigenetic modulation, which is similar to vitamin C.

METHODS:We performed a pilot and non-inferiority study in healthy young women (n = 12), who consumed vitamin C (1 g/d) or 240 mL of blueberry juice (total polyphenols 300 mg and proanthocyanidin 76 mg/d) for 2 weeks. We analyzed 8-hydroxydeoxyguanosine (8-OHdG) and malondialdehyde (MDA) levels in their urine, and global and specific DNA methylation at the NAD(P)H quinone oxidoreductase 1 (NQO1), methylenetetrahydrofolate reductase (MTHFR), or DNA methyltransferase 1 (DNMT1) genes in their blood.

RESULTS:Urinary 8-OHdG levels were reduced by blueberry consumption rather than by vitamin C. The methylation (%) of the MTHFR was significantly decreased in blueberry-consumers and the antioxidant-susceptible subgroup, whose urinary MDA levels were decreased by the intervention. We also found a positive correlation between changes of urinary 8-OHdG and of DNA methylation at the MTHFR or the DNMT1 (P<0.05). However, the genetic polymorphism of the MTHFR (C677T in exon 4) did not affect any above markers.

CONCLUSIONS:Blueberry juice shows similar anti-oxidative or anti-premutagenic activity to vitamin C and the potential as a methylation inhibitor for the MTHFR and the DNMT1 in human.

The treatment of alopecia is limited by a lack of therapies that induce and sustain disease remission. Given the negative psychosocial impact of hair loss, patients that do not see significant hair restoration with conventional therapies often turn to complementary and alternative medicine (CAM). Although there are a variety of CAM treatment options on the market for alopecia, only a few are backed by multiple randomized controlled trials. Further, these modalities are not regulated by the Food and Drug Administration and there is a lack of standardization of bioactive in gredients in over-the-counter vitamins, herbs, and supplements. In this article, we provide a comprehensive review of the efficacy, safety, and tolerability of CAM, including natural products and mind and body practices, in the treatment of hair loss. Overall, there is a need for additional studies investigating CAM for alopecia with more robust clinical design and standardized, quantitative outcomes.

This is a prospective study to assess a complementary treatment for genital warts after laser vaporization. 62 patients were enrolled in two randomized groups: Al: laser vaporization alone. A2: laser vaporization, followed with Pidotimod plus vitamin C for 2 1/2 months. The latter treatment shortened the time of warts remission and marginally decreased the rate of the warts' recurrence: 81% versus 67% (N.S.). Despite the non-significant difference, this complementary treatment seems to have some efficiency.

Background Although the health effects of vitamin C are well known, its physiological effect on serum lipoproteins and microRNA still remain to be investigated, especially daily consumption of a high dosage. Objectives To investigate the physiological effect of vitamin C on serum lipoprotein metabolism in terms of its anti-oxidant and anti-glycation activities, and gene expression via microRNA regulation. Methods We analyzed blood parameters and lipoprotein parameters in young subjects (n = 46, 22± 2 years old) including smokers who consumed a high dose of vitamin C (1250 mg) daily for 8 weeks. Results Antioxidant activity of serum was enhanced with the elevation of Vit C content in plasma during 8 weeks consumption. In the LDL fraction, the apo-B48 band disappeared at 8 weeks post-consumption in all subjects. In the HDL fraction, apoA-I expression was enhanced by 20% at 8 weeks, especially in male smokers. In the lipoprotein fraction, all subjects showed significantly reduced contents of advanced glycated end products and reactive oxygen species (ROS). Triglyceride (TG) contents in each LDL and HDL fraction were significantly reduced in all groups following the Vit C consumption, suggesting that the lipoprotein was changed to be more anti-inflammatory and atherogenic properties. Phagocytosis of LDL, which was purified from each individual, into macrophages was significantly reduced at 8-weeks post-consumption of vitamin C. Anti-inflammatory and anti-senescence effects of HDL from all subjects were enhanced after the 8-weeks consumption. The expression level of microRNA 155 in HDL3 was reduced by 49% and 75% in non-smokers and smokers, respectively. Conclusion The daily consumption of a high dose of vitamin C for 8 weeks resulted in enhanced anti-senescence and anti-atherosclerotic effects via an improvement of lipoprotein parameters and microRNA expression through anti-oxidation and anti-glycation, especially in smokers.

Current evidence supports a significant association between fruit and vegetable intake and health. In this study, we assessed the effect of consuming a vegetable-soup"gazpacho"on vitamin C and biomarkers of oxidative stress and inflammation in a healthy human population. We also examined the association between vitamin C and F(2)-isoprostanes (8-epiPGF(2alpha)), uric acid (UA), prostaglandin E(2) (PGE(2)), monocyte chemotactic protein-1 (MCP-1), and the cytokines, tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-6. Gazpacho is a Mediterranean dish defined as a ready-to-use vegetable soup, containing approximately 80% crude vegetables rich in vitamin C. Subjects (6 men, 6 women) enrolled in this study consumed 500 mL/d of gazpacho corresponding to an intake of 72 mg of vitamin C. On d 1, subjects consumed the gazpacho in one dose; from d 2 until the end of the study, d 14, 250 mL was consumed in the morning and 250 mL in the afternoon. Blood was collected before drinking the soup (baseline) and on d 7 and 14. Baseline plasma vitamin C concentrations did not differ between men and women (P = 0.060). Compared with baseline, the vitamin C concentration was significantly higher on d 7 and 14 of the intervention in both men and women (P<0.05). Baseline plasma levels of UA and F(2)-isoprostanes were higher (P

OBJECTIVES:To explore the interrelationship and mediating effect of factors that are beneficial (i.e., antioxidants) and harmful (i.e., inflammation and oxidative stress) to the relationship between sleep and cardiometabolic health.

DESIGN:Cross-sectional data from the 2005-2006 National Health and Nutrition Examination Survey.

SETTING:Nationally representative population sample from the US.

PARTICIPANTS:Age≥ 20 y with sleep data; final analytical sample of N = 2,079.

INTERVENTIONS:N/A.

MEASUREMENTS AND RESULTS:Metabolic syndrome was classified according to the Joint Interim Statement, and sleep duration was categorized as very short, short, adequate, and long sleepers (≤4, 5-6, 7-8, and ≥9 h per night, respectively). The indirect mediation effect was quantified as large (≥ 0.25), moderate (≥ 0.09), modest (≥ 0.01), and weak (<0.01). In general, inflammation was above the current clinical reference range across all sleep duration categories, whereas oxidative stress was elevated among short and very short sleepers. Select sleep duration-cardiometabolic health relationships were mediated by C-reactive protein (CRP),γ-glutamyl transferase (GGT), carotenoids, uric acid, and vitamins C and D, and were moderated by sex. Specifically, moderate-to-large indirect mediation by GGT, carotenoids, uric acid, and vitamin D were found for sleep duration-waist circumference and systolic blood pressure relationships, whereas vitamin C was a moderate mediator of the sleep duration-diastolic blood pressure relationship.

CONCLUSIONS:Several factors related to inflammation, oxidative stress, and antioxidant status were found to lie on the casual pathway of the sleep duration-cardiometabolic health relationship. Further longitudinal studies are needed to confirm our results.

Phytochemicals and micronutrients represent a growing theme in antimicrobial defense; however, little is known about their anti-borreliae effects of reciprocal cooperation with antibiotics. A better understanding of this aspect could advance our knowledge and help improve the efficacy of current approaches towards Borrelia sp. In this study, phytochemicals and micronutrients such as baicalein, luteolin, 10-HAD, iodine, rosmarinic acid, and monolaurin, as well as, vitamins D3 and C were tested in a combinations with doxycycline for their in vitro effectiveness against vegetative (spirochetes) and latent (rounded bodies, biofilm) forms of Borrelia burgdorferi and Borrelia garinii. Anti-borreliae effects were evaluated according to checkerboard assays and supported by statistical analysis. The results showed that combination of doxycycline with flavones such as baicalein and luteolin exhibited additive effects against all morphological forms of studied Borrelia sp. Doxycycline combined with iodine demonstrated additive effects against spirochetes and biofilm, whereas with fatty acids such as monolaurin and 10-HAD it produced FICIs of indifference. Additive anti-spirochetal effects were also observed when doxycycline was used with rosmarinic acid and both vitamins D3 and C. Antagonism was not observed in any of the cases. This data revealed the intrinsic anti-borreliae activity of doxycycline with tested phytochemicals and micronutrients indicating that their addition may enhance efficacy of this antibiotic in combating Borrelia sp. Especially the addition of flavones balcalein and luteolin to a doxycycline regimen could be explored further in defining more effective treatments against these bacteria.

Previous studies in this laboratory have shown that gamma-ray ionizing radiation in combination with oltipraz, a radioprotective agent, enhances hepatic microsomal epoxide hydrolase (mEH) and glutathione S-transferase (GST) expression. The present study was designed to investigate the effects of dexamethasone on the radiation-inducible expression of mEH and rGST genes and on the vitamin C and E-induced radioprotective effects in association with the expression of the genes. Treatment of rats with a single dose of dexamethasone (0.01-1 mg/kg, p.o.) caused a dose-dependent decrease in the constitutive mEH gene expression at 24 hr. The radiation-inducible mEH mRNA level (threefold increase after 3 Gy gamma-irradiation) was decreased by 21% and 88% by dexamethasone at the doses of 0.1 and 1 mg/kg, respectively. Although dexamethasone alone caused 2- to 5-fold increases in the hepatic rGSTA2 mRNA level, rats treated with dexamethasone prior to 3 Gy irradiation exhibited 80%-93% suppression in the radiation-inducible increases in the rGSTA2 mRNA level. The inducible rGSTA3 and rGSTA5 mRNA levels were also significantly decreased by dexamethasone, whereas the rGSTM1 mRNA level was reduced to a lesser extent. Vitamin C and/or E, however, failed to enhance the radiation-inducible increases in hepatic mEH and rGST mRNA levels. Whereas rats exposed to 3 Gy irradiation with or without vitamin C treatment (30 or 200 mg/kg/day, p.o., 2 days) exhibited approximately threefold increases in the mEH and rGSTA2/3/5 mRNA levels relative to untreated animals, dexamethasone treatment (1 mg/kg, p.o.) resulted in 64%-96% decreases in the mRNA levels at 24 hr. The inducible rGSTM1/2 mRNA levels in the vitamin C/E-treated rats were approximately 50% suppressed by dexamethasone. Although vitamin C and/or E treatment (200 mg/kg/day, p.o., 2 days) improved the 30-day survival rates of the 8 Gy gamma-irradiated mice from 39% up to 74%, the improved survival rate of gamma-irradiated animals was reduced to 30% by dexamethasone pretreatment (1 mg/kg/day, 2 days). The mean survival time of dexamethasone-treated animals was reduced to approximately 2 days from 14 days in the animals with total body irradiation alone. No significant hematologic changes were observed in mice at 10 days after dexamethasone plus gamma-irradiation, as compared with irradiation alone. These results demonstrate that: dexamethasone substantially suppresses radiation-inducible mEH, rGSTA and rGSTM expression in the liver; vitamins C/E exhibit radioprotective effects without enhancing radiation-inducible mEH and GST gene expression; and inhibition of radiation-inducible mEH and rGST gene expression in the vitamin C- and E-treated animals by dexamethasone was highly correlated with reduction in the survival rate and the mean survival time of gamma-irradiated animals.

OBJECTIVE:To determine the implications of supplemental vitamin C for pregnant tobacco smokers and its effects on the prevalence of pediatric asthma, asthma-related mortality, and associated costs.

STUDY DESIGN:A decision-analytic model built via TreeAge compared the outcome of asthma in a theoretical annual cohort of 480,000 children born to pregnant smokers through 18 years of life. Vitamin C supplementation (500 mg/day) with a standard prenatal vitamin was compared to a prenatal vitamin (60 mg/day). Model inputs were derived from the literature. Deterministic and probabilistic sensitivity analyses assessed the impact of assumptions.

RESULT:Additional vitamin C during pregnancy would prevent 1637 cases of asthma at the age of 18 per birth cohort of pregnant smokers. Vitamin C would reduce asthma-related childhood deaths and save $31,420,800 in societal costs over 18 years per birth cohort.

CONCLUSION:Vitamin C supplementation in pregnant smokers is a safe and inexpensive intervention that may reduce the economic burden of pediatric asthma.

Vitamin C, available in its reduced form (ascorbic acid; AA) and in its oxidized form (dehydroascorbic acid; DHA), may act in physiological conditions as an antioxidant or pro-oxidant. The aim of this study is to evaluate the cytotoxic effects of pharmacological doses of AA in a human colorectal adenocarcinoma cell line (WiDr) in vitro, through spectrophotometry, clonogenic assays and flow cytometry, and in vivo with xenotransplanted Balb/c nu/nu mice. The results show that the reduced form of vitamin C induces an anti-proliferative and cytotoxic effect in adenocarcinoma colorectal cells under study. The results obtained in vivo after treatment with AA showed a large reduction in the rate of tumor growth. Such understanding can guide decisions about which colorectal cancer patients might potentially benefit from vitamin C pharmacologic therapy.