scholarly journals Exogenous Antioxidants—Double-Edged Swords in Cellular Redox State: Health Beneficial Effects at Physiologic Doses versus Deleterious Effects at High Doses

2010 ◽  
Vol 3 (4) ◽  
pp. 228-237 ◽  
Author(s):  
Jaouad Bouayed ◽  
Torsten Bohn

The balance between oxidation and antioxidation is believed to be critical in maintaining healthy biological systems. Under physiological conditions, the human antioxidative defense system including e.g., superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione (GSH) and others, allows the elimination of excess reactive oxygen species (ROS) including, among others superoxide anions (O2.-), hydroxyl radicals (OH.), alkoxyl radicals (RO.) and peroxyradicals (ROO.). However, our endogenous antioxidant defense systems are incomplete without exogenous originating reducing compounds such as vitamin C, vitamin E, carotenoids and polyphenols, playing an essential role in many antioxidant mechanisms in living organisms. Therefore, there is continuous demand for exogenous antioxidants in order to prevent oxidative stress, representing a disequilibrium redox state in favor of oxidation. However, high doses of isolated compounds may be toxic, owing to prooxidative effects at high concentrations or their potential to react with beneficial concentrations of ROS normally present at physiological conditions that are required for optimal cellular functioning. This review aims to examine the double-edged effects of dietary originating antioxidants with a focus on the most abundant compounds, especially polyphenols, vitamin C, vitamin E and carotenoids. Different approaches to enrich our body with exogenous antioxidants such as via synthetic antioxidants, diets rich in fruits and vegetables and taking supplements will be reviewed and experimental and epidemiological evidences discussed, highlighting that antioxidants at physiological doses are generally safe, exhibiting interesting health beneficial effects.

2005 ◽  
Vol 48 (7) ◽  
pp. 993-1001 ◽  
Author(s):  
Rulian Ricardo Faria ◽  
Vanessa Costhek Abílio ◽  
Christian Grassl ◽  
Cibele Cristina Chinen ◽  
Luciana Takahashi Ribeiro Negrão ◽  
...  

Blood ◽  
1996 ◽  
Vol 88 (1) ◽  
pp. 184-193 ◽  
Author(s):  
HU Lutz ◽  
P Stammler ◽  
E Jelezarova ◽  
M Nater ◽  
PJ Spath

Abstract Intravenously applied human IgG has beneficial effects in treating inflammatory diseases, presumably because it has a complement attenuating role. This role of IgG was studied in vitro by following C3 activation and inactivation in sera that were supplemented with exogenous human IgG and incubated with immune aggregates. IgG added at 2 to 10 mg/mL stimulated the physiologic inactivation of C3b-containing complexes twofold to threefold in 20% sera. This, in turn, lowered the overall C3 activation by 28%, as new C3 convertases primarily assembled on C3b-containing complexes. Exogenous IgG (5 mg/mL) also stimulated inactivation of purified C3b2-IgG complexes, whereby their half-life dropped from 3–4 to 1.5 minutes in 20% serum. IgG appeared to act like a modulator of factor H and I because it did not stimulate inactivation of C3b-containing complexes in factor I-deficient serum. Thus, the known partial protection of C3bn-IgG complexes from inactivation by factor H and I was downregulated by high concentrations of IgG. The ability of high doses of IgG to stimulate complement inactivation is a novel regulatory role of IgG. This may be one of the molecular principles for its therapeutic efficacy in treating complement-mediated inflammations.


Molecules ◽  
2019 ◽  
Vol 24 (3) ◽  
pp. 453 ◽  
Author(s):  
Wiktoria Blaszczak ◽  
Wojciech Barczak ◽  
Julia Masternak ◽  
Przemysław Kopczyński ◽  
Anatoly Zhitkovich ◽  
...  

Ascorbic acid (vitamin C) has been gaining attention as a potential treatment for human malignancies. Various experimental studies have shown the ability of pharmacological doses of vitamin C alone or in combinations with clinically used drugs to exert beneficial effects in various models of human cancers. Cytotoxicity of high doses of vitamin C in cancer cells appears to be related to excessive reactive oxygen species generation and the resulting suppression of the energy production via glycolysis. A hallmark of cancer cells is a strongly upregulated aerobic glycolysis, which elevates its relative importance as a source of ATP (Adenosine 5′-triphosphate). Aerobic glycolysis is maintained by a highly increased uptake of glucose, which is made possible by the upregulated expression of its transporters, such as GLUT-1, GLUT-3, and GLUT-4. These proteins can also transport the oxidized form of vitamin C, dehydroascorbate, permitting its preferential uptake by cancer cells with the subsequent depletion of critical cellular reducers as a result of ascorbate formation. Ascorbate also has a potential to affect other aspects of cancer cell metabolism due to its ability to promote reduction of iron(III) to iron(II) in numerous cellular metalloenzymes. Among iron-dependent dioxygenases, important targets for stimulation by vitamin C in cancer include prolyl hydroxylases targeting the hypoxia-inducible factors HIF-1/HIF-2 and histone and DNA demethylases. Altered metabolism of cancer cells by vitamin C can be beneficial by itself and promote activity of specific drugs.


2015 ◽  
Vol 16 (2) ◽  
pp. 157-161 ◽  
Author(s):  
Dragan M. Pavlović ◽  
Merdin Š. Markišić ◽  
Aleksandra M. Pavlović

Abstract Vitamins are necessary factors in human development and normal brain function. Vitamin C is a hydrosoluble compound that humans cannot produce; therefore, we are completely dependent on food intake for vitamin C. Ascorbic acid is an important antioxidative agent and is present in high concentrations in neurons and is also crucial for collagen synthesis throughout the body. Ascorbic acid has a role in modulating many essential neurotransmitters, enables neurogenesis in adult brain and protects cells against infection. While SVCT1 enables the absorption of vitamin C in the intestine, SVCT2 is primarily located in the brain. Ascorbate deficiency is classically expressed as scurvy, which is lethal if not treated. However, subclinical deficiencies are probably much more frequent. Potential fields of vitamin C therapy are in neurodegenerative, cerebrovascular and affective diseases, cancer, brain trauma and others. For example, there is some data on its positive effects in Alzheimer’s disease. Various dosing regimes are used, but ascorbate is safe, even in high doses for protracted periods. Better designed studies are needed to elucidate all of the potential therapeutic roles of vitamin C.


2020 ◽  
Vol 11 (SPL4) ◽  
pp. 1405-1409
Author(s):  
Omodamiro O.D ◽  
Ewa-ibe C ◽  
Jimoh M.A ◽  
Ajah O

Free radical-mediated cell damage can be prevented by well-known antioxidant vitamins such as Vitamins E and C, and it has been reported that Paracetamol can cause hepatotoxicity at high doses. This study evaluated the efficacy of the combination of Vitamin C and Vitamin E in the prevention of renal and hepatic cell damage caused by paracetamol toxicity. Twenty-eight male albino rats were grouped into seven of four rats per group. Vitamin C at prophylactic dosage; (200mg, 150mg, 100mg, 50mg, 25mg) and Vitamin E at prophylactic dosage; (500iu, 400iu, 300iu, 200iu, 100iu) were administered orally to the rats in groups 1 through 5, respectively with concomitant administration 1000mg/kg bw of paracetamol twice daily for seven days. Group 6 was administered 1000mg/kg of paracetamol only (untreated), and Group 7 served as the normal control. The results revealed a significantly (P < 0.05) increase in serum ALT, AST, ALP, Urea and Creatinine of the group administered 1000mg/kg of paracetamol only. The prophylactic doses of ascorbic acid and α-tocopherol significantly (P < 0.05) decrease serum ALT, AST, ALP, Urea and Creatinine level compared to the untreated rats. This study validates that co-administration of ascorbic acid and α-tocopherol at the proposed prophylactic dosages could be used in the prevention of renal and hepatic cell damage caused by paracetamol toxicity.


Neurosurgery ◽  
2010 ◽  
Vol 67 (2) ◽  
pp. 546-546 ◽  
Author(s):  
Ali Razmkon ◽  
Ahmad Sadidi ◽  
Ehsan Sherafat-Kazemzadeh ◽  
Ali Mehrafshan ◽  
Atefeh Bakhtazad

2002 ◽  
Vol 21 (4) ◽  
pp. 223-230 ◽  
Author(s):  
M Oncu ◽  
F Gultekin ◽  
E Karaöz ◽  
I Altuntas ◽  
N Delibas

Nephrotoxicity induced by chlorpyrifos-ethyl (CE) and ameliorating effects of melatonin and vitamin E plus vitamin C were evaluated in rats exposed to CE. Experimental groups were as follows: control (C), CE treated (CE), vitamin E plus vitamin C treated (Vit), melatonin treated (Mel), vitamin E plus vitamin C plus CE treated (Vit+CE), and melatonin plus CE treated (Mel+CE). The rats in the CE, Vit+CE and Mel+CE groups were administered orally with CE in two equal doses of 41 mg/kg body weight (0.25 LD50). Melatonin and vitamins E and C were administrated intramuscularly at the doses of 10, 150 and 200 mg/kg, respectively. The levels of thiobarbituric acid reactive substance (TBARS) and antioxidant potential (AOP), and the activities of glutathione peroxidase (GSHPx), catalase (CAT) and superoxide dismutase (SOD) were studied in the homogenates of kidney tissue. There were no significant differences in the activities of SOD and CAT between the experimental groups. The level of TBARS increased significantly (P<0.05) while AOP decreased significantly (P<0.05) in the CE group compared with the C group. GSH-Px activity was significantly (P<0.05) lower in the CE group and higher in the melatonin group than the control group. Histopathological changes were found in the kidney tissue of rats treated with CE. These were infiltration in mononuclear cells at perivascular and peritubular areas, hydropic degenerations in tubule epithelium and glomerular sclerosis. The severity of the lesions was reduced by administration of vitamins and melatonin. These results suggest that CE increases lipid peroxidation and decreases AOP by increasing oxidative stress, and that high doses of melatonin and a combination of vitamin E plus vitamin C considerably reduce the toxic effect of CE on kidney tissue of rats.


Animals ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1739
Author(s):  
Mohamed A. Hashem ◽  
Sahar S. Abd El Hamied ◽  
Eman M. A. Ahmed ◽  
Shimaa A. Amer ◽  
Aziza M. Hassan

The current investigation evaluated the alleviating effects of vitamin C and vitamin E on oxidative stress, hematobiochemical, and histopathological changes in the kidney induced by copper sulfate (CuSO4) toxicity in chickens. Two hundred and fifty-one-day-old male broiler chicks were randomly allotted into five experimental groups (five replicates/group, ten chicks/replicate): 1st group—basal diet with no additives (control group), 2nd group—basal diet complemented with CuSO4 (300 mg/kg diet), 3rd group—basal diet with CuSO4 (300 mg/kg diet) + vitamin C (250 mg/kg diet), 4th group—basal diet with CuSO4 (300 mg/kg diet) + vitamin E (250 mg/kg diet), and 5th group—basal diet with CuSO4 (300 mg/kg diet) + vitamin C (250 mg/kg diet) + vitamin E (250 mg/kg diet) for a 42 day feeding period. The results showed a significant reduction in red blood cells (RBCs), hemoglobin (Hb) concentration, and hematocrit values as well as total leukocyte counts (WBCs), lymphocyte, heterophil, and monocyte counts in the CuSO4-intoxicated birds (2.42 × 106/µL, 9.54 g/dL, 26.02%, 15.80 × 103/µL, 7.86 × 103/µL, 5.26 × 103/µL, and 1.18 × 103/µL, respectively, at the 6th week) compared to (2.79 × 106/µL, 10.98 g/dL, 28.46%, 21.07 × 103/µL, 10.84 × 103/µL, 7.12 × 103/µL, and 1.60 × 103/µL, respectively) in the control group. Moreover, CuSO4-intoxicated birds showed hypoglycemia with a rise in serum uric acid and creatinine levels (122.68, 5.18, and 0.78 mg/dL at the 6th week) compared to (159.46, 4.41, and 0.61 mg/dL) in the control group. The CuSO4 toxicity in birds induced oxidative stress, indicated by a high serum malondialdehyde level (MDA) and diminished activity of the antioxidant enzymes (glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD)) (2.01 nmol/mL, 37.66 U/mL, and 2.91 U/mL, respectively, at the 6th week) compared to (1.34 nmol/mL, 57.00 U/mL, 4.99 U/mL, respectively) in the control group. High doses of Cu exposure caused severe microscopic alterations in kidney architecture. The addition of vitamins C and E, singularly or in combination, displayed a beneficial effect in alleviating these harmful effects of Cu toxicity. These findings showed the possible mitigating impacts of dietary antioxidants on the hematobiochemical alterations, oxidative stress, and kidney damage induced by CuSO4 toxicity.


2021 ◽  
Author(s):  
Ajaya Kumar Ayyappan Unnithan

Abstract Background and Objectives: There is no pharmacological treatment with proven efficacy against coronavirus disease-19. Certain micronutrients have roles in the maintenance of an effective immune system. From the point of view of public health, it will be good to adopt a nutrional strategy to enhance the immunity of the general population against viral diseases.Method and Study design: A review was done to now the evidence for the antiviral and immunomodulatory properties of micronutrients. A search was done in Pubmed, Scopus, and Google Scholar for the nutrients with proven effect against viral infection. Experimental studies, clinical studies, reviews, and meta-analyses were studied descripitively.Results: There are experimental studies about the effects of micronutrients against viral infection. Vitamins such as A, B6, B12, C, D, E, and folate, and trace elements such as zinc, selenium, iron, magnesium, and copper boost the immune response. The antioxidants like vitamin C and vitamin E can help in controlling the ‘cytokine storm’, produced by excessive inflammation. Vitamin D can increase anti-inflammatory cytokines. Selenium and zinc can protect the lungs in acute respiratory distress syndrome. There are many meta-analyses on the randomized controlled trials (RCT) about the effect of micronutrients on viral infection. The analyses of the trials supplementing vitamin C, vitamin D, vitamin E, and selenium have shown significance. Conclusions: There is level 2A evidence for the beneficial effects of vitamins and micronutrients in improving the immunity against viral infections. So a programme for nutritional supplementation of these can help in fighting the pandemic.


2021 ◽  
Vol 11 (12) ◽  
pp. 83-90
Author(s):  
Franck Arnaud Moukobolo Kinsangou ◽  
Henriette Poaty ◽  
Dimitry Moudiongui Mboungou

Background: Numerous reviews report the beneficial effects of alpha tocopherol in preventive supplementation and also as an adjuvant in the treatment of some pathologies (cardiovascular, cancers). In this work, we analyzed the effects of vitamin E at high doses on some biochemical parameters. Methods: Thirty-two adult male and female mice (CD1 albino mice) were randomly selected for a 4-week experiment. The mice were supplemented with alpha tocopherol at doses of 150, 400 and 750mg/day. With a high dietary intake of vitamin E Results: According to our analyses, we can note Excess weight predominated in groups 4 to 7. All the blood lipid parameters showed an abnormal concentration, as of the 400 mg dose of α-T-acetate. Hyperglycemia and hyperlipidemia were observed. These variations were more pronounced for total cholesterol and triglycerides than for HDL and LDL fractions. Conclusion: The study showed significant effects of high-dose α-T supplementation on biochemical parameters, mainly hyperglycemia and dyslipidemia. Key words: Vitamin E, Alpha-tocopherol, blood biochemical parameters.


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