Inhibitory effect of high dose ascorbic acid on inflammatory edema

The ability of ascorbic acid (AA) as an antioxidant to suppress the inflammatory reaction was investigated. Carrageenan-induced foot pad edema was produced in the right hind foot of anesthetized mice (n=22). Subsequently, Group A (n=11) received 25 mg AA in saline (IP) and Group B, an equal volume of saline. After 2 1/2 hrs the animals were sacrificed and increase in weight of the amputated right paw over the amputated left paw was expressed as percentage edema (PE). The PE in Group A was 43.8±5.9, and in Group B was 59.3±3.9 (p<0.05, unpairedt-test). The same experiment was repeated with the AA administered 10 minutes prior to injury. The change in edema was not statistically significant. It is concluded that high dose AA suppresses edema if given after but not before injury.     

The effect of high ascorbic acid doses on the course of pregnancy in the guinea pig and on the progeny

Summary The work is a continuation of investigations made earlier by the author (Bull. of Exp. Biol. and Med. No. 10, 1962) on the effect of ascorbic acid on the function of the genital organs of female guinea pigs. This work contains data on the effect produced by ascorbic acid excess on the course of pregnancy and on the progeny.It was shown that prolonged (during the whole course of pregnancy) daily per oral administration of ascorbic acid to female guinea pigs (high doses –500 mg per animal, and physiological doses 50 mg per animal) led to pathology of pregnancy and of the progeny.This pathology is manifested by a considerable percentage of abortions at various periods, as well as by stillbirths and by birth of nonviable progeny. Histomorphological examination of internal organs of stillborn and nonviable animals revealed marked tissue hypoxia.Presented by Active Member A. P. Nikolaeva AMN SSSR Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 57, No. 4, pp. 105–108, April, 1964     

Evidence of rebound effect with ascorbic acid

The urinary excretion pattern of ascorbic acid in two subjects who had been taking a large amount of ascorbic acid (10 g per day) and later reverted to a small intake (125 mg per day) is described. The ascorbic acid concentration in the 24-hour urine samples was measured over a 40-day collection of this period. The mean urinary ascorbic acid excretion during the loading period of the two subjects was about 2 g per day. Upon termination of the high intake of ascorbic acid, urinary ascorbic acid excretion dropped to presupplementation levels within 6 days. Urinary ascorbic acid of the two subjects continued to decrease to below basal level, and remained at abnormally low levels for 10 and 12 days respectively. We hypothesize that the high intake of ascorbic acid has induced the formation of increased amounts of enzymes that help convert the ascorbic acid into other substances and that these substances are valuable. Some possible physiological actions of these ascorbic acid metabolites are discussed.     

The effect of high and low doses of cycloheximide on nucleolar ribonucleic acid synthesis.

In resting rat liver a dose of cycloheximide (1 mg. per kg.) inhibits leucine incorporation by 80 per cent whereas doses above 15 mg. per kg. inhibit it more than 90 per cent, when tested at 90 minutes following intraperitoneal injection. Initial stimulation of incorporation of orotate into total cellular, nuclear, and nucleolar fractions was seen at all doses tested. After 3 hours, however, marked suppression of incorporation particularly into nucleolar RNA was seen at 5 mg. per kg. and above while 1 mg. per kg. continued to stimulate. At 5 hours there was continued marked inhibition of RNA synthesis by 30 mg. per kg. and slight depression of RNA synthesis even by 1 mg. per kg. Preliminary ultrastructural studies failed to show objective nucleolar alterations even after 5 hours of cycloheximide treatment at a dose of 30 mg. per kg. No direct effect of several concentrations of cycloheximide on RNA synthesis was seen in an in vitro nucleolar system.     

The effect of ascorbic acid on the human lymphocyte

Human lymphocytes obtained from normal, healthy subjects were studied for their in vitro responses to ascorbic acid. Ascorbic acid inhibited the incorporation of 3H-uridine as well as the phytohaemagglutin-associated enhancement of 3H-thymidine incorporation.     

百里醌抑制乳腺癌血管生长的实验研究

 目的: 探讨百里醌对乳腺癌血管生长的作用于及其机制。方法: 不同浓度百里醌作用于人脐静脉内皮细胞(HUVECs)及人乳腺癌细胞株MCF-7后,应用CCK-8法检测细胞活力,流式细胞术检测细胞凋亡,小管形成实验检测内皮细胞体外小管形成能力,Western blot法检测内皮细胞中cleaved caspase-3、p-ERK及p-AKT的蛋白水平;建立裸鼠乳腺癌移植瘤模型,完全随机法分成对照组和百里醌组,免疫组织化学法检测乳腺肿瘤组织中CD31的表达,TUNEL法检测移植瘤细胞凋亡。结果: 百里醌(20~80 nmol/L)对MCF-7细胞生长无明显抑制作用,20 nmol/L、40 nmol/L和80 nmol/L百里醌作用于内皮细胞24 h后,细胞存活率分别为(74.3±5.9)％、(68.7±5.6)％和(47.9±4.3)％;20 nmol/L、40 nmol/L和80 nmol/L百里醌作用于MCF-7细胞24 h后,细胞凋亡率分别为(2.6±0.3)％、(2.4±0.3)％和(4.6±0.4)％,而相应的内皮细胞凋亡率分别为(21.5±3.7)％、(23.8±2.9)％和(27.8±3.1)％,内皮细胞较乳腺癌细胞对百里醌反应更敏感(P<0.05);20 nmol/L、40 nmol/L和80 nmol/L百里醌作用于内皮细胞1 h后,内皮细胞小管形成长度分别为(0.88±0.12)mm、(0.76±0.10)mm和(0.54±0.08)mm,与对照组相比,差异有统计学意义(P<0.05);80 nmol/L百里醌作用于内皮细胞24 h后,内皮细胞中cleaved caspase-3的水平上调, AKT和ERK磷酸化被抑制,与对照组比较差异有统计学意义(P<0.05);免疫组化检测移植瘤组织中CD31结果显示,百里醌组IA值明显少于对照组(P<0.05);TUNEL检测结果显示,百里醌组IA值明显增大(P<0.05)。结论: 百里醌可抑制体内外乳腺癌血管生长,降低p-ERK及p-AKT的水平可能是其作用机制之一。     

Japanese Shiba dogs possessing erythrocytes with high Glut-1 activity and high ascorbic acid recycling capacity

Glut-1 was discovered in erythrocytes of some Japanese Shiba dogs. They have Glut-1 as well as Glut-4 in erythrocytes, while other Shiba dogs and other breeds have only Glut-4. Dog erythrocytes with Glut-1 showed much higher affinity for entry of glucose and oxidized ascorbic acid and greater capacity for ascorbic acid (AA) recycling than those with only Glut-4. Dog is among numerous AA-synthesizing species that normally do not have Glut-1 in erythrocytes. However, this variant of dog is the first example of an AA-synthesizing animal which maintains Glut-1 in erythrocytes throughout life. Shiba dogs can be a new animal model for further understanding the mechanism of regulation and functions of AA in the organism.     

Effects of ascorbic acid on high GSH and normal dog erythrocytes (I)

Dog erythrocytes with high GSH and normal GSH concentrations were compared under effects of ascorbic acid. In the presence of glucose, these two types of erythrocytes showed a similar increase in intracellular ascorbic acid without change in GSH levels. Addition of iron (Fe³⁺) to the incubation medium enhanced ascorbic acid accumulation. In the absence of glucose, GSH fell markedly in both types of erythrocyte and less ascorbic acid accumulated in normal GSH cells than high GSH cells. With iron, normal cells showed GSH depletion and marked methaemoglobin formation. Lipid peroxidation with ascorbic acid and iron increased at a similar rate in both types of erythrocyte and was inhibited by catalase. Ferricyanide reduction in both erythrocytes loaded with ascorbic acid were similar and increased with glucose or catalase. There was a high correlation between intracellular ascorbic acid content and ferricyanide reduction. These results suggest that high GSH and normal GSH dog erythrocytes have a similar capacity for accumulating ascorbic acid and for reducing ferricyanide. However, normal GSH erythrocytes are more susceptible to the oxidant effect of ascorbic acid than high GSH cells; this is probably due to a smaller GSH reserve, which is exhausted more rapidly under oxidative stress.     

In vitro effect of ascorbic acid on infectivity of herpesviruses and paramyxoviruses.

Suspensions of herpes simplex virus types 1 and 2, cytomegalovirus, and parainfluenzavirus type 2 were inactivated within 24 h when treated at 37 degrees C with 1 mg (5.05 mM) of copper-catalyzed sodium ascorbate per ml. The infectivity titer of respiratory syncytial virus was reduced substantially after 24 h but required 48 h for inactivation. Under these conditions, inactivation of these viruses was also successfully achieved with 5.68 mM catalyzed ascorbic acid. Copper (Cu2+), when added with the ascorbate solution at 5 micrograms/ml (0.022 mM), exhibited a catalytic effect on the inactivation of these viruses. The rate of inactivation was affected by the incubation temperature, time of exposure, and the virus concentration. Ascorbate concentrations as high as 10 mg/ml (50.5 mM) demonstrated only a minimum increase in effect on viral inactivation. The loss of infectivity did not alter either the hemagglutination or complement fixation qualities of the antigens.     

Evidence for the involvement of glutamatergic system in the antinociceptive effect of ascorbic acid

This study examined the role of glutamatergic system in the ascorbic acid (AA)-induced antinociception in chemical behavioural models of nociception in mice. AA (0.3-10 mg/kg, i.p.) produced significant inhibition of both phases of formalin-induced licking, with mean ID50 values of 4.0 and 3.2 mg/kg and inhibitions of 56+/-4 and 60+/-7% for the early and second phase of the nociception caused by formalin, respectively. AA (1-5 mg/kg, i.p.) also produced significant inhibition of glutamate-induced nociception with mean ID50 value of 2.1 mg/kg and inhibition of 66+/-5%. Furthermore, AA (3 mg/kg, i.p.) caused marked inhibition of nociceptive response induced by intrathecal injection of glutamate, NMDA, AMPA, kainate and substance P, with inhibitions of 49+/-9, 42+/-7, 34+/-8, 38+/-5 and 65+/-8%, respectively. In contrast, AA at the same dose did not affect the biting response induced by the metabotropic agonist trans-ACPD. Taken together, present results indicate that AA, at low systemic doses, produces a rapid onset and consistent antinociception in mice when assessed in several models of chemical nociception, an action that is likely mediated by an interaction with ionotropic, but not metabotropic, glutamate receptors.     

The effect of ascorbic acid on cutaneous and nasal response to histamine and allergen

The effect of ascorbic acid (AA) on the skin wheal and flare response to histamine and allergen and on the nasal response to allergen was evaluated in eight adults with seasonal allergic rhinitis. The above parameters were measured after 3 days of AA administration (2 gm/day) and again after 3 days of a similar-appearing lactose placebo. An additional study was conducted in which six subjects took 0 (placebo), 1, 2, and 4 gm/day of AA to determine the dose-response effect of AA on histamine skin tests. Overall there was no difference in skin or nasal reactivity between AA and placebo regimens. The findings in this study suggest that AA in relatively high doses would have no beneficial effects on symptoms resulting from allergen exposure and that AA in doses of up to 4 gm/day will not suppress the histamine skin response.     

百里醌对血管生成及胰腺癌生长的影响

目的: 探讨百里醌对血管生成和胰腺癌生长的影响及其机制。方法: 采用贴壁选择法培养人脐血内皮祖细胞(EPCs),细胞免疫组化检验细胞中血管内皮生长因子受体-2(VEGFR-2)、VIII因子和 CD34表达,证实细胞属性;观察不同浓度(10 nmol/L、20 nmol/L和40 nmol/L)百里醌对EPCs小管形成的影响;不同浓度(20 μmol/L、40 μmol/L和80 μmol/L)百里醌作用人胰腺癌细胞株PANC-1后,Western blotting检测胰腺癌细胞中血管内皮生长因子(VEGF)表达的变化;建立裸鼠胰腺癌原位移植瘤模型,分成对照组和百里醌组,实验结束后观察百里醌对裸鼠胰腺癌生长的抑制作用;免疫组织化学法检测裸鼠胰腺肿瘤组织中Ki-67、CD34和VEGF的阳性表达。结果: 体外成功培养出人脐血EPCs,百里醌可显著抑制体外EPCs小管形成;并抑制体外人胰腺癌PANC-1细胞中VEGF的表达;与对照组相比较,百里醌可明显抑制荷瘤裸鼠中胰腺肿瘤生长,并下调Ki-67、CD34和VEGF在胰腺肿瘤组织中的阳性表达。结论: 百里醌可抑制体内外血管生长,有望作为治疗胰腺癌的血管抑制药物。     

The effect of ascorbic acid on infection of chick-embryo ciliated tracheal organ cultures by coronavirus

Summary Chick embryo tracheal organ cultures showed increased resistance to infection by a coronavirus after exposure to ascorbate, while chick respiratory epithelium and allantois-on-shell preparations showed no increase in resistance to infection by an influenza virus or a paramyxovirus.With 1 Figure