High Doses of Vitamin C and Leukemia: In Vitro Update

According to recent investigations, the parenteral application of ascorbic acid (vitamin C) at high doses has significant antitumor activity in in vitro assays. The goal of our experiment was to determine the possible potentiating effect of application of high dose pH-neutralized ascorbic acid to the normal oncothermia treatment method. The NMRI mice were inoculated with C26 murine colon carcinoma cell line subcutaneously at both of their femoral regions and were kept till the tumors reached symmetrically 10 mm in diameter. We created four experimental groups, containing 5 male and 5 female animals in each. Both vitamin-C and oncothermia treatments were applied once; ascorbic acid was applied intra-peritoneally. Oncothermia treatment was applied only to the right limb tumor; the other side will be used as internal control. After the treatment, the animals were sacrificed, and all tumors were removed and analyzed histopathologically. Our main question centers on the comparison of the cell destruction ratio of the various applied treatment regimes, and studies the possible synergy or additive cross-potentiating of the methods. The results of this experiment turned out to be controversial, since the ascorbic acid did not change the remission rate of the allografts and showed no synergy with oncothermia.

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High doses of vitamin E and vitamin C influence in vitro rumen microbial activity

Animal Feed Science and Technology ◽

10.1016/j.anifeedsci.2013.05.010 ◽

2013 ◽

Vol 183 (3-4) ◽

pp. 210-214 ◽

Cited By ~ 11

Author(s):

Franco Tagliapietra ◽

Mirko Cattani ◽

Hanne H. Hansen ◽

Giovanni Bittante ◽

Stefano Schiavon

Keyword(s):

Vitamin E ◽

Vitamin C ◽

Microbial Activity ◽

High Doses

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Vitamin C, From Supplement to Treatment: A Re-Emerging Adjunct for Cancer Immunotherapy?

Frontiers in Immunology ◽

10.3389/fimmu.2021.765906 ◽

2021 ◽

Vol 12 ◽

Author(s):

Léonce Kouakanou ◽

Christian Peters ◽

Christine E. Brown ◽

Dieter Kabelitz ◽

Leo D. Wang

Keyword(s):

Vitamin C ◽

Cancer Therapies ◽

Delay Tumor Growth ◽

Anti Cancer ◽

Challenges And Opportunities ◽

High Doses ◽

Direct Killing

Vitamin C (VitC), in addition to its role as a general antioxidant, has long been considered to possess direct anti-cancer activity at high doses. VitC acts through oxidant and epigenetic mechanisms, which at high doses can exert direct killing of tumor cells in vitro and delay tumor growth in vivo. Recently, it has also been shown that pharmacologic-dose VitC can contribute to control of tumors by modulating the immune system, and studies have been done interrogating the role of physiologic-dose VitC on novel adoptive cellular therapies (ACTs). In this review, we discuss the effects of VitC on anti-tumor immune cells, as well as the mechanisms underlying those effects. We address important unanswered questions concerning both VitC and ACTs, and outline challenges and opportunities facing the use of VitC in the clinical setting as an adjunct to immune-based anti-cancer therapies.

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In Vivo Effect of Suloctidil as an Antiplatelet Agent

Thrombosis and Haemostasis ◽

10.1055/s-0038-1646799 ◽

1979 ◽

Vol 41 (03) ◽

pp. 465-474 ◽

Cited By ~ 7

Author(s):

Marcia R Stelzer ◽

Thomas S Burns ◽

Robert N Saunders

Keyword(s):

Ex Vivo ◽

Antiplatelet Agent ◽

Ratio Method ◽

Platelet Aggregate ◽

Permanent Effect ◽

Platelet Aggregates ◽

5 Ht Uptake ◽

High Doses

SummaryThe relationship between the effects of suloctidil in vivo as an antiplatelet agent and in vitro as a modifier of platelet serotonin (5-HT) parameters was investigated. Suloctidil was found to be effective in reducing platelet aggregates formation in the retired breeder rat as determined using the platelet aggregate ratio method (PAR) with an ED50 of 16.1 mg/kg 24 hours post administration. In contrast to the hypothesis that 5-HT depletion is involved in the anti-aggregatory mechanism of suloctidil, no correlation was found between platelet 5- HT content and this antiplatelet activity. Reduction of platelet 5-HT content required multiple injections of high doses (100 mg/kg/day) of suloctidil. Suloctidil administration for 8 days at 100 mg/kg/day, which lowered platelet 5-HT content by 50%, resulted in no permanent effect on ex vivo platelet 5-HT uptake or thrombin-induced release, nor alteration in the plasma 5-HT level. However, these platelets exhibited a short-lived, significant increase in percent leakage of 5-HT after 30 minutes of incubation. Therefore, suloctidil treatment at high doses may with time result in platelet 5-HT depletion, however this effect is probably not related to the primary anti-aggregatory activity of the drug.

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Daunorubicin and Platelet Function

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650125 ◽

1981 ◽

Vol 45 (01) ◽

pp. 038-042 ◽

Cited By ~ 9

Author(s):

M E Pogliani ◽

R Fantasia ◽

G Lambertenghi-Deliliers ◽

E Cofrancesco

Keyword(s):

Electron Microscope ◽

Cellular Membrane ◽

Hemorrhagic Diathesis ◽

Clot Retraction ◽

Freezing And Thawing ◽

Platelet Factor ◽

High Doses ◽

Very High ◽

Platelet Functions

SummaryThe influence of Daunorubicin on some platelet functions in vitro was investigated, using different concentrations of the drug (0.01-0.02-0.04 μg/ml). Daunorubicin was shown to inhibit Collagen and Thrombin induced platelet aggregation and the intensity of inhibition depended on both drug concentration and the time of preincubation.Daunorubicin was also shown to inhibit the release reaction, the platelet prostaglandin pathway and the availability platelet factor 3; the drug at concentrations for clinical use does not damage the platelet membrane, as is the case with the freezing and thawing test, in platelet uptake of 14C-serotonin and as confirmed by the electron microscope. When very high doses (0.16 mg) of Daunorubicin are used, lysis of the platelets can be observed and this is confirmed under the electron microscope by the presence of empty platelets with fractures at the level of the cytoplasmic membrane.Finally, Daunorubicin causes irreversible inhibition of reptilase clot-retraction, even if this is less severe than with Vincristine. Working with gel-filtered platelets, it would appear that the inhibition exercised by the drug on platelet reactions is not caused through modifications in Ca++ metabolism.The authors suggest that Daunorubicin, at the dosages used clinically, induces in vitro thrombocytopathy without damaging the cellular membrane as confirmed by the electron microscope.This impairment of platelet functions could play a part in hemorrhagic diathesis observed during Daunorubicin therapy.

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Effects of Two Different Doses of Hirudin on APTT, Determined with Eight Different Reagents

Thrombosis and Haemostasis ◽

10.1055/s-0038-1653754 ◽

1995 ◽

Vol 73 (02) ◽

pp. 219-222 ◽

Cited By ~ 4

Author(s):

Manuel Monreal ◽

Luis Monreal ◽

Rafael Ruiz de Gopegui ◽

Yvonne Espada ◽

Ana Maria Angles ◽

...

Keyword(s):

Ex Vivo ◽

Anticoagulant Activity ◽

Subcutaneous Administration ◽

In Vitro Study ◽

Ex Vivo Model ◽

Suitable Candidate ◽

Significant Prolongation ◽

High Doses ◽

Different Doses

SummaryThe APTT has been considered the most suitable candidate to monitor the anticoagulant activity of hirudin. However, its use is hampered by problems of standardization, which make the results heavily dependent on the responsiveness of the reagent used. Our aim was to investigate if this different responsiveness of different reagents when added in vitro is to be confirmed in an ex vivo study.Two different doses of r-hirudin (CGP 39393), 0.3 mg/kg and 1 mg/kg, were administered subcutaneously to 20 New Zealand male rabbits, and the differences in prolongation of APTT 2 and 12 h later were compared, using 8 widely used commercial reagents. All groups exhibited a significant prolongation of APTT 2 h after sc administration of hirudin, both at low and high doses. But this prolongation persisted 12 h later only when the PTTa reagent (Boehringer Mannheim) was used. In general, hirudin prolonged the APTT most with the silica- based reagents.In a further study, we compared the same APTT reagents in an in vitro study in which normal pooled plasma was mixed with increasing amount of hirudin. We failed to confirm a higher sensitivity for silica- containing reagents. Thus, we conclude that subcutaneous administration of hirudin prolongs the APTT most with the silica-based reagents, but this effect is exclusive for the ex vivo model.

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Role of vitamin C in gastric cancer

10.33118/oap.radiol/01.001 ◽

2018 ◽

Vol 01 (1) ◽

Author(s):

Takalkar U Vidyadhar

Keyword(s):

Gastric Cancer ◽

Vitamin C ◽

Gastric Juice ◽

Oxidative Dna Damage ◽

Preventive Measure ◽

Dietary Factors ◽

Preventive Strategy ◽

H Pylori

Gastric cancer is a multifactorial disease with complex interplay of environmental and genetic factors. Helicobacter pylori (H. pylori) infestation has been identified as the most important etiological agent in the pathogenesis of gastric cancer. Also, the role of dietary factors that is low consumption of fruits and vegetables have been found to be associated with gastric cancer. Among the dietary factors, antioxidants especially vitamin C has been found to confer the strongest protection against gastric cancer. Its anti-proliferative and pro-apoptotic action has been suggested in vitro. Because of its antioxidant activity, it protects cells against oxidative DNA damage caused by toxic effects of reactive oxygen species. It also inhibits production of carcinogenic N-nitroso compound in the stomach. The person with H. pylori infection has low levels of vitamin C in their gastric juice and levels of vitamin C normalizes on eradication of H. pylori. Vitamin C levels are high in gastric mucosa and gastric juice, sometimes more than that of in plasma. But gastric pathological conditions cause lowered secretion of vitamin C into gastric juice. Effect of H. pylori on vitamin C in gastric juice is reversible and on eradication of H. pylori, it returns to normal level. Hence, eradication of H. pylori and chemoprevention with antioxidant supplementation will be an effective preventive strategy to reduce the incidence of gastric cancer and related mortality. Vitamin C and gastric cancer is an area of potential interest for researchers as a preventive measure. Keywords: Vitamin C, H. pylori, gastric cancer.

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Effect of Adding Resistant Maltodextrin to Pasteurized Orange Juice on Bioactive Compounds and Their Bioaccessibility

Foods ◽

10.3390/foods10061198 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1198

Author(s):

Elías Arilla ◽

Purificación García-Segovia ◽

Javier Martínez-Monzó ◽

Pilar Codoñer-Franch ◽

Marta Igual

Keyword(s):

Vitamin C ◽

Antioxidant Capacity ◽

Bioactive Compounds ◽

Orange Juice ◽

Control Sample ◽

Water Soluble ◽

In Vitro Digestibility ◽

Total Phenols ◽

Resistant Maltodextrin

Resistant maltodextrin (RMD) is a water-soluble and fermentable functional fiber. RMD is a satiating prebiotic, reducer of glucose and triglycerides in the blood, and promoter of good gut health, and its addition to food is increasingly frequent. Therefore, it is necessary to study its potential effects on intrinsic bioactive compounds of food and their bioaccessibility. The aim of this study was to evaluate the effect of adding RMD on the bioactive compounds of pasteurized orange juice with and without pulp, and the bioaccessibility of such compounds. RMD was added at different concentrations: 0 (control sample), 2.5%, 5%, and 7.5%. Ascorbic acid (AA) and vitamin C were analyzed using HPLC, whereas total phenols, total carotenoids (TC), and antioxidant capacity were measured using spectrophotometry. After that, sample in vitro digestibility was assessed using the standardized static in vitro digestion method. The control orange juice with pulp presented significantly higher values of bioactive compounds and antioxidant capacity than the control orange juice without pulp (p < 0.05). RMD addition before the juice pasteurization process significantly protected all bioactive compounds, namely total phenols, TC, AA, and vitamin C, as well as the antioxidant capacity (AC) (p < 0.05). Moreover, this bioactive compound protective effect was higher when higher RMD concentrations were added. However, RMD addition improved phenols and vitamin C bioaccessibility but decreased TC and AA bioaccessibility. Therefore, the AC value of samples after gastrointestinal digestion was slightly decreased by RMD addition. Moreover, orange pulp presence decreased total phenols and TC bioaccessibility but increased AA and vitamin C bioaccessibility.

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Vitamin C—Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination

Nutrients ◽

10.3390/nu13020615 ◽

2021 ◽

Vol 13 (2) ◽

pp. 615

Author(s):

Martin Doseděl ◽

Eduard Jirkovský ◽

Kateřina Macáková ◽

Lenka Krčmová ◽

Lenka Javorská ◽

...

Keyword(s):

Ascorbic Acid ◽

Vitamin C ◽

Iron Absorption ◽

Plasma Concentrations ◽

Physiological Role ◽

Renal Stones ◽

Anti Oxidant ◽

High Doses ◽

Epigenetic Processes

Vitamin C (L-ascorbic acid) has been known as an antioxidant for most people. However, its physiological role is much larger and encompasses very different processes ranging from facilitation of iron absorption through involvement in hormones and carnitine synthesis for important roles in epigenetic processes. Contrarily, high doses act as a pro-oxidant than an anti-oxidant. This may also be the reason why plasma levels are meticulously regulated on the level of absorption and excretion in the kidney. Interestingly, most cells contain vitamin C in millimolar concentrations, which is much higher than its plasma concentrations, and compared to other vitamins. The role of vitamin C is well demonstrated by miscellaneous symptoms of its absence—scurvy. The only clinically well-documented indication for vitamin C is scurvy. The effects of vitamin C administration on cancer, cardiovascular diseases, and infections are rather minor or even debatable in the general population. Vitamin C is relatively safe, but caution should be given to the administration of high doses, which can cause overt side effects in some susceptible patients (e.g., oxalate renal stones). Lastly, analytical methods for its determination with advantages and pitfalls are also discussed in this review.

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