Hemolysis attributed to high dose vitamin C:Two case reports

BACKGROUND High-dose vitamin C treatment(HVCT)can reduce the adverse effect of chemotherapy and enhance the effect of antitumor therapy,which has been considered one of the safest alternative treatments.However,the severity of its adverse effects may have been underestimated.The most serious adverse effect is hemolysis,which may result in acute kidney injury or death.Although glucose-6-phosphate dehydrogenase(G6PD)deficiency is considered to be the main cause,the probability and pathological mechanism are not completely understood,leading to a lack of effective and standardized treatment methods.CASE SUMMARY Two patients with colorectal cancer developed hemolytic anemia after using 1 g/kg HVCT.In contrast to previous cases,the lowest hemoglobin level in the two cases was<50 g/L,which was lower than previously reported.This may be because Case 1 had chronic hepatitis B for many years,which caused abnormal liver reserve function,and Case 2 had grade II bone marrow suppression.Both patients improved and were discharged after blood replacement therapy.Our cases had the most severe degree of hemolysis but the best prognosis,suggesting that our treatment may be helpful for rescue of drug-induced hemolysis.This is the first review of the literature on hemolysis caused by HVCT,and we found that all patients with G6PD deficiency developed hemolysis after HVCT.CONCLUSION G6PD deficiency should be considered as a contraindication to HVCT,and it is not recommended for patients with bone marrow suppression,moderate-tosevere anemia,hematopoietic abnormalities,or abnormal liver and kidney function.Early blood purification and steroid therapy may avoid acute kidney injury or death caused by HVCT-related hemolytic anemia.

Causal relationship between circulating vitamin C and 25-hydroxyvitamin D concentrations and common mental disorders-a Mendelian randomization study

Mental disorders seriously affect people’s health and social stability.This Mendelian randomization(MR)study was designed to investigate the causal relationship between circulating vitamin C(VC)or 25-hydroxyvitamin D(25(OH)D)levels and mental disorders.The data used for the MR analysis were derived from the summary genome-wide association studies(GWAS)database for VC and 25(OH)D and from the Finn Gen consortium for fourteen mental disorders.Based on the inverse variance weighted(IVW)method,we found a potential causal association between circulating VC and anxiety disorders(IVW:OR=1.139,95%CI:1.023-1.269,P=0.018).However,no causal association was found between VC or 25(OH)D and other mental disorders(P>0.05).In the reverse MR analysis,individuals with Alzheimer’s disease was causally associated with higher concentrations of circulating VC(P=0.012),while individuals with anxiety disorders had a negative association between the concentrations of 25(OH)D(P=0.012).However,the current evidence does not support a causal relationship between VC or 25(OH)D and other mental disorders.In addition,there was no causal association between circulating VC and 25(OH)D(P>0.05).Future studies are needed to confirm these findings and to elucidate the mechanisms of potential causality.

Protective Effect of Ascorbate-Lysine on Carbon Tetrachloride and Alcohol-Induced Liver Injury in Mice

As an essential amino acid, lysine boosts protein synthesis (Nestor et al1997). Yao et al demonstrated that, lysine also exerts protective effect against the isch-emiclesion of brain. Meanwhile, vitamin C is a natural antioxidant, which has undisputable protectiveaction against free radical damages. In order to ascertain whether their combination could affordbetter effect, we have investigated the prophylactic effect of the couplant ascorbate-lysine inliver injuries.

TR-ESR Investigation on Reaction of Vitamin C with Excited Triplet of 9,10-phenanthrenequinone in Reversed Micelle Solutions

Time-resolved electron spin resonance has been used to study quenching reactions between the antioxidant Vitamin C （VC） and the triplet excited states of 9,10-phenanthrenequinone （PAQ） in ethylene glycol-water （EG-H2O） homogeneous and inhomogeneous reversed micelle solutions. Reversed micelle solutions were used to be the models of physiological environment of biological cell and tissue. In PAQ/EG-H2O homogeneous solution, the excited triplet of PAQ （3PAQ＊） abstracts hydrogen atom from solvent EG. In PAQ/VC/EG-H2O solution, 3pAQ＊ abstracts hydrogen atom not only from solvent EG but also from VC. The quenching rate constant of 3pAQ＊ by VC is close to the diffusion-controlled value of 1.41 × 108 L/（mol.s）. In hexadecyltrimethylammonium bromide （CTAB）/EG-H2O and aerosol OT （AOT）/EG- H2O reversed micelle solutions, 3pAQ＊ and VC react around the water-oil interface of the reversed micelle. Exit of 3pAQ＊ from the lipid phase slows down the quenching reaction. For Triton X-100 （TX-100）/EG-H2O reversed micelle solution, PAQ and VC coexist inside the hydrophilic polyethylene glycol core, and the quenching rate constant of 3pAQ＊ by VC is larger than those in AOT/EG-H2O and CTAB/EG-H2O reversed micelle solutions, even a little larger than that in EG-H2O homogeneous solution. The strong emissive chemically induced dynamic electron polarization of As＇- resulted from the effective TM spin polarization transfer in hydrogen abstraction of 3pAQ＊ from VC.

Effects of Exogenous Vc on Seed Germination and Physiological Properties of Oil Sunflower(Helianthus annuus) under Salt Stress

[Objective] This study aimed to provide the theoretical and technical basis for alleviating salt damages in production practice of oil sunflower （Helianthus annuus）. [Method] Seeds of oil sunflower were used as experimental materials and treated with 120 mmol/L NaCI solution and 0-200 mg/L Vc solution during the germina- tion process, to investigate the effects of exogenous Vc on seed germination and physiological properties of oil sunflower under salt stress. [Result] Under salt stress, with the increase of Vc concentration, germination potential and germination rate of oil sunflower seeds, superoxide dismutase （SOD） and peroxidase （POD） activities and proline （Pro） content of oil sunflower seedlings increased first and then declined, which reached the maixmum in 80 mg/L Vc treatment, 120 mg/L Vc treatment and 80 mg/L Vc treatment, respectively; malondialdehyde （MDA） content of oil sunflower seedlings declined first and then increased, which reached the minimum in 160 mg/L Vc treatment. [Conclusion] To varying degrees, Vc could improve germination potential and germination rate of oil sunflower seeds and promote seedling growth under salt stress, thus alleviating the damages of salt stress to seed germination and seedling growth of oil sunflower.

Effect of methoxychlor on antioxidant system of goat epididymal sperm in vitro

Aim: To evaluate the effect of methoxychlor on the antioxidant system of goat epididymal sperm. Methods:Epididymis of adult goat was obtained from local slaughter houses and sperm were collected by chopping the epididymisin modified Ringer's phosphate solution (RPS). After several washings, the sperm samples were dispersed in RPS andincubated with methoxychlor (1μmol/L, 10μmol/L and 100μmol/L) and methoxychlor + vitamin C (100μmol/Leach) for 3 h at 32℃. After incubation, the sperm motility and viability were assessed. An aliquot of sperm samplewas homogenized, centrifuged and used for the assay of superoxide dismutase, glutathione peroxidase, glutathione re-ductase and lipid peroxidation. Results; In methoxychlor-incubated sperm and in sperm co-incubated with methoxy-chlor and vitamin C, the sperm motility and viability showed no significant changes as compared to the correspondingcontrols. In methoxychlor-incubated sperm the activity of superoxide dismutase, glutathione reductase and glutathioneperoxidase were decreased while lipid peroxidation was increased in a dose-dependent manner. Co-incubation of spermwith methoxychlor and vitamin C showed no changes in the activity of superoxide dismutase, glutathione reductase andglutathione peroxidase and in the level of lipid peroxidation. Conclusion; Methoxychlor induced oxidative stress inepididymal sperm of goats by decreasing the levels of antioxidant enzymes. Co-incubation of sperm with methoxychlorand vitamin C, a natural antioxidant, reversed the effect of methoxychlor. (Asian J Androl 2001 Dec; 3; 285 - 288)

Crystallization Thermodynamic and Kinetic Behaviors of Vitamin C in Batch Crystallizer

The bench-scale cooling crystallization for ternary solution of L-ascorbic acid (Vitamin C) was studied.The solid-liquid phase diagram of Vitamin C-water-ethanol system was obtained on the basis of differential scanning calorimeter (DSC) curves. The heat of crystallization of Vitamin C was calculated with the aid of quantitative analysis. According to the population balance equation under unsteady state, the rates of nucleation and growth were determined. The parameters of crystallization kinetics equations were estimated by regression of experimental data. Crystal morphology and size were determined with x-ray diffraction and TA Ⅱ Coulter Counter.

Micronutrient deficiencies in patients with chronic atrophic autoimmune gastritis: A review

Chronic atrophic autoimmune gastritis (CAAG) is an organ-specific autoimmune disease characterized by an immune response, which is directed towards the parietal cells and intrinsic factor of the gastric body and fundus and leads to hypochlorhydria, hypergastrinemia and inadequate production of the intrinsic factor. As a result, the stomach&#x02019;s secretion of essential substances, such as hydrochloric acid and intrinsic factor, is reduced, leading to digestive impairments. The most common is vitamin B12 deficiency, which results in a megaloblastic anemia and iron malabsorption, leading to iron deficiency anemia. However, in the last years the deficiency of several other vitamins and micronutrients, such as vitamin C, vitamin D, folic acid and calcium, has been increasingly described in patients with CAAG. In addition the occurrence of multiple vitamin deficiencies may lead to severe hematological, neurological and skeletal manifestations in CAAG patients and highlights the importance of an integrated evaluation of these patients. Nevertheless, the nutritional deficiencies in CAAG are largely understudied. We have investigated the frequency and associated features of nutritional deficiencies in CAAG in order to focus on any deficit that may be clinically significant, but relatively easy to correct. This descriptive review updates and summarizes the literature on different nutrient deficiencies in CAAG in order to optimize the treatment and the follow-up of patients affected with CAAG.

Sperm quality improvement after natural anti-oxidant treatment of asthenoteratospermic men with leukocytospermia

Aim： To study the immune-modulating and anti-oxidant effects of beta-glucan, papaya, lactoferrin, and vitamins C and E on sperm characteristics of patients with asthenoteratozoospermia associated with leucocytosis. Methods： Fifty-one patients referred to our Sterility Center for semen analysis were selected. Sperm parameters were assessed before and after patient＇s treatment with beta-glucan, lactoferrin, papaya, and vitamins C and E. DNA damage was assessed by the acridine orange test and sperm structural characteristics were evaluated by transmission electron microscopy. Results： After 90 days of treatment, an increase in the percentage of morphologically normal sperm （17.0 ± 5.2 vs. 29.8 ± 6.5） and total progressive motility （19.0± 7.8 vs. 34.8 ± 6.8） were detected. Structural sperm characteristics as well as chromatin integrity were also improved after treatment. In terms of leukocyte concentration in seminal fluid, a significant reduction was recorded （2.2 ± 0.9 vs. 0.9± 0.2）. Conclusion： The treatment of an inflammatory process by the synergic action of immune modulators and anti-oxidants could protect sperm during maturation and migration, leading to improved sperm function. （Asian JAndrol 2008 Mar;. 10： 201-206）

Impact of diet on long-term decline in gastric cancer incidence in Poland

AIM:To examine the relationship between the trends in food consumption and gastric cancer morbidity in Poland.METHODS:The study was based on gastric cancer incidence rates and consumption of vegetables,fruit,vitamin C and salt in Poland between 1960 and 2006.Food consumption data were derived from the national food balance sheets or household budget surveys.Spearman correlation coefficients were used to estimate the relationship between the variables.RESULTS:A negative correlation was found between vegetables(-0.70 both for men and women;P < 0.0001),fruit(-0.65 and-0.66;P < 0.0001) and vitamin C(-0.75 and-0.74;P < 0.0001) consumption and stomach cancer incidence rates.The same applied to the availability of refrigerators in the household(-0.77 and-0.80;P < 0.0001).A decline in these rates could also be linked to reduction in salt intake.CONCLUSION:The decline of gastric cancer incidence probably resulted from increased consumption of vegetables,fruit and vitamin C and a decrease in salt consumption.

Comprehensive evaluation of 20 pomegranate(Punica granatum L.) cultivars in China

Recent investigations on pomegranate products have significantly increased and successfully drawn consumers’ attention to nutritional and medicinal values, promoting the pomegranate industry’s development worldwide. However, little information on pomegranates grown in China is available. Morphological and chemical characterizations of fruits and arils from 20 pomegranate cultivars in six regions of China were investigated. Combined with overall scores by principal component analysis, ‘Yushiliu No. 1’, ‘Taishanhong No. 2’, ‘Tunisia’ and ‘Mollar’ were promising cultivars, and Chinese researchers bred the first two. It was surprising that ‘Mollar’ had bigger fruit size and more aril moisture grown in China than in Spain. Cultivars with higher anthocyanin content in arils were ‘Turkey’, ‘Moyu’ and ‘Red Angel’, which might be used as the source of natural red food colourants. While red husk ‘Hongruyi’ and ‘Hongshuangxi’ with higher vitamin C, aril moisture and lower titratable acid in arils, might also be promising cultivars for further various utilization. Furthermore, the comparison of ‘Tunisia’ fruits from four regions revealed that cultivation locations had more influence on fruit traits than genotypes. Maturity index classification was established for Chinese pomegranate cultivars. Therefore, the results would provide a valuable guide for agricultural cultivation, industrial utilization, and breeding.

Dietary and socio-economic factors in relation to Helicobacter pylori re-infection

AIM:To examine if dietary and socio-economic factors contribute to Helicobacter pylori(H pylori)re-infection. METHODS:The population of patients consisted of subjects in whom H pylori infection had been successfully treated in the past.Patients were divided into two groups:Ⅰ-examined group(111 persons with H pylori re-infection)andⅡ-control group(175 persons who had not been re-infected).The respondents were interviewed retrospectively on their dietary habits and socio-economic factors. RESULTS:A statistically significant lower frequency of fermented dairy products(P<0.0001),vegetables (P=0.02),and fruit(P=0.008)consumption was noted among patients with H pylori re-infection as compared to those who had not been re-infected. CONCLUSION:High dietary intake of probiotic bacteria,mainly Lactobacillus,and antioxidants,mainly vitamin C(contained in fruit and vegetables),might decrease the risk of H pylori re-infection.

Impact of poly chlorinated biphenyl (Aroclor 1254) and vitamin C on antioxidant system of rat ventral prostate

Aim: To evaluate the effect of polychlorinated biphenyls (PCB) and vitamin C on ventral prostatic antioxidant system in adult male rats. Methods: A group of 20 adult male rats were administered ip Aroclor 1254 in corn oil at a dose of 2 mg·kg-1·day-1 for 30 days. Ten control rats were administered only the vehicle. After 30 days the treated rats were divided at random into 2 sub-groups of 10 animals each. One sub-group received vitamin C at a dose of 500 mg·kg-1·day-1 for 10 days. The other group was maintained as Aroclor 1254 control. Twenty-four hours after the last treatment the rats were killed by decapitation. Ventral prostatic homogenate was prepared and used for the estimation of enzymatic antioxidants, including superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST) and hydrogen peroxide (H2O2), lipid peroxidation (LPO) and prostatic acid phosphatase. The serum levels of total T3, total T4, TSH, testosterone and estradiol were also assayed. Results: The body weight and ventral prostatic weight were reduced in PCB treated rats. The activities of SOD, CAT, GST and acid phosphatase were decreased while the levels of H2O2 and lipid peroxidation were increased in the ventral prostate of PCB treated rats. Administration of vitamin C restored these parameters. Serum levels of thyroid hormones, estradiol and testosterone were decreased in PCB treated animals. Administration of vitamin C restored the thyroid hormone levels. Conclusion: PCB induces oxidative stress and decreases the antioxidant enzymes in the ventral prostate of adult male rats; the effects could be reversed by the administration of vitamin C.

Melatonin reduces traumatic brain injury-induced oxidative stress in the cerebral cortex and blood of rats

Free radicals induced by traumatic brain injury have deleterious effects on the function and antioxidant vitamin levels of several organ systems including the brain. Melatonin possesses antioxidant effect on the brain by maintaining antioxidant enzyme and vitamin levels. We in-vestigated the effects of melatonin on antioxidant ability in the cerebral cortex and blood of traumatic brain injury rats. Results showed that the cerebral cortex β-carotene, vitamin C, vita-min E, reduced glutathione, and erythrocyte reduced glutathione levels, and plasma vitamin C level were decreased by traumatic brain injury whereas they were increased following melatonin treatment. In conclusion, melatonin seems to have protective effects on traumatic brain inju-ry-induced cerebral cortex and blood toxicity by inhibiting free radical formation and supporting antioxidant vitamin redox system.

Lipophilic Enhance of Vitamin C Protective Activity Against Free-radical-induced Damage in vivo

A group of experimental rats under free radical damage are given various amounts of a lipophilic vitamin C(ascorbyl-6-laurate, VC-12), and its parent compound, vitamin C, respectively. It has been found that the effects of 1 12 mmol/kg VC-12 on decreasing triglyceride(TG), total cholesterol(TC), low density lipoprotein cholesterol (LDL-c) and lipid peroxide(LPO), and increasing high density lipoprotein cholesterol(HDL-c) and superoxide dismutase(SOD) are similar to those of 2 27 mmol/kg vitamin C. In addition, VC-12(1 12 mmol/kg) can increase the prostacycline(PGI 2) and decrease the thromboxane(TXA 2) even better than vitamin C(2 27 mmol/kg). The above facts demonstrate that the antioxidative activity of VC-12 is higher than twice that of vitamin C. So, ascorbyl-6-laurate may be a novel antioxidant drug against free radical damage.

Antioxidants vitamin E and C attenuate hepatic fibrosis in biliary-obstructed rats

AIM： To investigate whether antioxidants vitamin E and C can retard development of hepatic fibrosis in the bilian/obstructed rats. METHODS： Fifty Wistar albino rats were randomly assigned to 5 groups （10 rats in each）. Bile duct was ligated in 40 rats and they were treated as follows： group vitC, vitamin C 10 mg/kg sc daily; group vitE, vitamin E 15 mg/kg sc daily; group vitEC, both of the vitamins; bile duct-ligated （BDL, control） group, physiological saline sc. The fifth group was assigned to sham operation. At the end of fourth week, the rats were decapitated, and hepatic tissue biochemical collagen content and collagen surface area were measured. Hepatic tissue specimens were histopathologically evaluated according to Scheuer system. Serum hyaluronate levels were measured by ELISA method. RESULTS： Despite being higher than sham group, hepatic collagen level was significantly decreased in each of the vitC, vitE and vitEC groups （32.7 ± 1.2, 33.8 ± 2.9, 36.7 ± 0.5 ）μg collagen/mg protein, respectively） compared to BDL （48.3 ± 0.6 mg collagen/g protein） （P 〈 0.001 for each vitamin group）. Each isolated vitamin C, isolated vitamin E and combined vitamin E/C supplementation prevented the increase in hepatic collagen surface density （7.0% ± 1.1%, 6.2% ± 1.7%, 12.3% ± 2.0%, respectively） compared to BDL （17.4% ± 5.6%） （P 〈 0.05 for each）. The same beneficial effect of vitamin C, vitamin E and combined vitamin E/C treatment was also observed on the decrease of serum hyaluronate levels compared to BDL group （P 〈 0.001）. The relative liver and spleen weights, serum transaminases, cholestatic enzymes, bilirubins and histopathological inflammation scores were not different between the antioxidant treatment groups and the control. However, fibrosis staging scores were obviously reduced only in the vitamin E/C combination group （vit EC： 2.4 ± 0.8 vs BDL： 3.1 ± 0.7; P 〈 0.05）. CONCLUSION： Each antioxidant vitamin E, vitamin C and their combination retard hepatic fibrosis in biliary-obstructed rats. Oxidative stress may play a role in the pathogenesis of hepatic fibrosis in secondary biliary cirrhosis.

Effect of dietary supplementation of vitamin C on growth, reactive oxygen species, and antioxidant enzyme activity of Apostichopus japonicus(Selenka) juveniles exposed to nitrite

Different amounts of vitamin C were added to diets fed to juveniles （2.5＋0.15 g） of sea cucumber Apostichopus japonicus （Selenka） in an attempt to reduce the stress response of specimens exposed to nitrite stress. A commercial feed was used as the control diet and three experimental diets were made by supplementing 1 000, 1 500, or 2 000 mg vitamin C/kg diet to control diet separately in a 45-day experiment. Sea cucumbers were exposed to three different levels （0.5, 1.0, and 1.5 mg/L） of nitrite stress for 4, 8, and 12 h at four time intervals （0, 15, 30, and 45 d）. Growth of the animals was recorded during the experiment. Reactive oxygen species （ROS） （i.e. hydroxyl free radical （-OH）, malondialdehyde （MDA） and total antioxidant capacity （T-AOC）） and antioxidant enzyme activities （i.e., superoxide dismutase （SOD） and eatalase （CAT）） were measured. Response surface methodology （RSM） was used to analyze the effect of multiple factors on ROS indices and enzyme activities. Weight gain （WG） and special growth rate （SGR） of vitamin C supplementation groups were significantly higher than those of control group （P〈0.05）. The levels of-OH and MDA increased under exposure time extending and nitrite concentration increasing, whereas T-AOC level decreased. SOD and CAT activities increased at 4 h and 8 h and decreased at 12 h. During the days in which the animal consumed experimental diets, the levels of-OH and MDA decreased and that of T-AOC increased. This result suggests that diets containing vitamin C could reduce the nitrite stress response in the animals and increase their antioxidant capacity. The multifactor regression equation of growth performance, ROS indices, and duration of feeding results suggest that vitamin C supplementation of 1 400-2 000 mg/kg diet for 29-35 days could reduce effectively the effects of nitrite exposure.

Preventive and Therapeutic Potential of Vitamin C in Mental Disorders

In this review,we summarize the involvement of vitamin C in mental disorders by presenting available evidence on its pharmacological effects in animal models as well as in clinical studies.Vitamin C,especially its reduced form,has gained interest for its multiple functions in various tissues and organs,including central nervous system（CNS）.Vitamin C protects the neuron against oxidative stress,alleviates inflammation,regulates the neurotransmission,affects neuronal development and controls epigenetic function.All of these processes are closely associated with psychopathology.In the past few decades,scientists have revealed that the deficiency of vitamin C may lead to motor deficit,cognitive impairment and aberrant behaviors,whereas supplement of vitamin C has a potential preventive and therapeutic effect on mental illness,such as major depressive disorder（MDD）,schizophrenia,anxiety and Alzheimer＇s disease（AD）.Although several studies support a possible role of vitamin C against mental disorders,more researches are essential to accelerate the knowledge and investigate the mechanism in this field.

Thermal Analysis of Vitamin C Affecting Low.temperature Oxidation of Coal

Simultaneous thermal analysis was used to study the influence of Vitamin C as possible chemical additive inhibiting coal oxidation process at low temperature. Some oxidation characteristics of Vitamin C affecting the coal oxidation were investigated at different heating rates. The TG-DSC data show that the impact of Vitamin C on coal oxidation process can be directly evaluated using ignition temperature and critical temperature. Comparison with the effect of water on coal oxidation shows that Vitamin C is more efficient than water. However, the blank experiment conducted with inert a-Al2O3 also suggests that Vitamin C can decompose at about 200 ℃, which limits the usage of Vitamin C on inhibiting coal oxidation.

Effects of Combined Instantaneous High-Pressure and MediumTemperature on the Retention of Total Vitamin Cin Wax Gourd Juices

Based on the instantaneous high-pressure(IHP)produced by high-pressure single pole-cylinder pump, the effects of combining this pressure with medium temperature on the retention of total vitamin C(Vc)in wax gourd juices were investigated under 20 - 80 MPa, 35 - 58℃, pH 3. 0 - 6. 0 and processing time 0-8 min. Results showed that the loss of Vc increased with elevated processing temperatures(50 MPa, 4 min). When the temperature of raw juices was 35℃, the retention of total Vc was higher under 40 - 60 MPa than that under the pressure < 40 MPa or > 60 MPa, and it was up to 94%(4 min). The retention of total Vc decreases slowly within 6 min, but rapidly after 6 min. The pH can also influence the retention of total Vc, and this retention can come to a highest point at pH 6.0.