Effect
of dietary vitamin C on compression injury of the spinal cord
in a rat mutant unable to synthesize ascorbic acid and its
correlation with that of vitamin E
Spinal Cord (United Kingdom), 1996, 34/4 (234-238)
The roles of vitamines after spinal cord injury were investigated
by evaluating the effects of dietary vitamin C on experimental
spinal cord injury in a mutant strain of Wistar rats unable
to synthesize ascorbic acid (ODS rats). Two groups of ODS
rats were given vitamin C-deficient or vitamin C-supplemented
diet for 1 week before injury. Motor disturbance induced
by spinal cord injury was found to be greater in the vitamin
C-deficient group. Histologically, the area of bleeding
in the spinal cord was also greater in the vitamin C-deficient
group. The levels of ascorbic acid and alpha-tocopherol
in the spinal cord tissue and serum decreased during and
after compression injury of the spinal cord. The decrease
of alpha-tocopherol was similar in the two groups. However,
the decrease of ascorbic acid was greater in the vitamin
C-supplemented group. These results indicated that their
protective effects against spinal cord injury are through
scavenging water-soluble free radicals by vitamin C and
lipid-soluble by vitamin E, and the effects of these vitamins
were suggested to be independent.
Cerebral astrocytes transport ascorbic acid and dehydroascorbic
acid through distinct mechanisms regulated by cyclic AMP.
J Neurochem (UNITED STATES) Jun 1997, 68 (6) p2378-85
Cerebral ischemia and trauma lead to rapid increases in
cerebral concentrations of cyclic AMP and dehydroascorbic
acid (DHAA; oxidized vitamin C), depletion of intracellular
ascorbic acid (AA; reduced vitamin C), and formation of
reactive astrocytes. We investigated astrocytic transport
of AA and DHAA and the effects of cyclic AMP on these transport
systems. Primary cultures of astrocytes accumulated millimolar
concentrations of intracellular AA when incubated in medium
containing either AA or DHAA. AA uptake was Na+-dependent
and inhibited by 4,4'-diisothiocyanostilbene-2, 2í-disulfonic
acid (DIDS), whereas DHAA uptake was Na+-independent and
DIDS-insensitive. DHAA uptake was inhibited by cytochalasin
B, D-glucose, and glucose analogues specific for facilitative
hexose transporters. Once inside the cells, DHAA was reduced
to AA. DHAA reduction greatly decreased astrocytic glutathione
concentration. However, experiments with astrocytes that
had been previously depleted of glutathione showed that
DHAA reduction does not require physiological concentrations
of glutathione. Astrocyte cultures were treated with a permeant
analogue of cyclic AMP or forskolin, an activator of adenylyl
cyclase, to induce cellular differentiation and thus provide
in vitro models of reactive astrocytes. Cyclic AMP stimulated
uptake of AA, DHAA, and 2-deoxyglucose. The effects of cyclic
AMP required at least 12 h and were inhibited by cycloheximide,
consistent with a requirement for de novo protein synthesis.
Uptake and reduction of DHAA by astrocytes may be a recycling
pathway that contributes to brain AA homeostasis. These
results also indicate a role for cyclic AMP in accelerating
the clearance and detoxification of DHAA in the brain.
Osmotic swelling stimulates ascorbate efflux from cerebral
astrocytes.
J Neurochem (UNITED STATES) Mar 1996, 66 (3) p1227-33
Ascorbate (reduced vitamin C) is an important enzyme cofactor,
neuromodulator, and antioxidant that is stored at millimolar
concentrations in the cytosol of cerebral astrocytes. Because
these cells swell during hyponatremia, cerebral ischemia,
sport of ascorbate. Ascorbate efflux from primary cultures
of rat astrocytes was rapidly (within 1 min) increased by
incubation in hypotonic medium. Efflux also increased when
astrocytes, which had been adapted to a hypertonic environment,
were swollen by transfer to isotonic medium. Swelling-induced
ascorbates efflux was inhibited by the anion-transport inhibitors
4,4'-diisothiocyanostilbene-2, 2 '-disulfonic acid (DIDS)
and 4,4'-dinitrostilbene-2, 2í-disulfonic acid (DNDS).
The pathway that mediates ascorbate efflux was found to
be selective because a larger anion, 2', 7í-bis(carboxyethyl)-5-(or
-6)-carboxyfluorescein (BCECF), was retained in the swollen
astrocytes. Na (+)-dependent ascorbate uptake into astrocytes
was inhibited slightly during the first minute of hypotonic
stress, indicating that the sodium ascorbate cotransporter
does not mediate swelling-induced efflux. Cell concentration
of authentic ascorbate was measured by HPLC with electrochemical
detection. When astrocytes were incubated in ascorbate-free
medium, hypotonicity decreased cell ascorbate concentration
by 50% within 3 min. When astrocytes were incubated in ascorbate-supplemented
hypotonic medium, intracellular ascorbate concentration
was restored within 10 min because uptake remained effective.
Many pathological conditions cause brain cell swelling and
formation of reactive oxygen species. Ascorbate release
during during astrocytic swelling may contribute to cellular
osmoregulation in the short-term and the scavenging of reactive
oxygen species.
Effect of allopurinol, sulphasalazine, and vitamin C on
aspirin induced gastroduodenal injury in human volunteers
United Kingdom Gut (United Kingdom), 1996, 38/4 (518-524)
Background - The mechanisms of aspirin induced gastroduodenal
injury are not fully understood. Aspirin induces the release
of reactive oxygen metabolites in animal models, which may
contribute to mucosal injury.
Aims - To investigate the effects of aspirin administered
with placebo or antioxidants on gastric mucosal reactive
oxygen metabolite release and gastroduodenal injury in human
volunteers.
Subjects - Fourteen healthy volunteers participated in
the study (seven male; mean age 27 years, range 20-40).
Methods - In a double blind, randomised, crossover study,
volunteers received aspirin 900 mg twice daily and either
placebo, allopurinol 100 mg twice daily, sulphasalazine
l g twice daily or vitamin C 1 g twice daily for three days.
Injury was assessed endoscopically and by quantifying mucosal
reactive oxygen metabolite release by measuring chemiluminescence
before and after each treatment. The effect on prostanoids
was determined by measuring ex vivo antral prostaglandin
E2 (PGE2) synthesis and serum thromboxane B2 (TXB2).
Results - No drug reduced any parameter of gastric injury
but vitamin C reduced duodenal injury assessed by Lanza
score (p < 0.005). Chemiluminescence increased after
aspirin both with placebo (p < 0.05) and vitamin C (p
< 0.05). Post-treatment chemiluminescence was lower in
subjects taking allopurinol (p < 0.05) or sulphasalazine
(p < 0.005) than in those taking placebo with aspirin.
Conclusions - In this study, aspirin induced gastric injury
was associated with reactive oxygen metabolite release.
This was reduced by sulphasalazine and allopurinol, although
macroscopic injury was not affected. Vitamin C, however,
was shown to have a previously unrecognised protective effect
against aspirin induced duodenal injury.
Hemodynamic effects of delayed initiation of antioxidant
therapy (beginning two hours after burn) in extensive third-degree
burns
Journal of Burn Care and Rehabilitation (USA), 1995, 16/6
(610-615)
The hemodynamic effects of the delayed initiation of antioxidant
therapy with high-dose vitamin C were studied in 12 guinea
pigs with third-degree burns over 70% of their body surface
area. All animals were resuscitated with Ringer's lactate
solution (RE) according to the Parkland formula (4 ml/kg/%
burn during the first 24 hours) from one-half to 2 hours
after burn, and the infusion rate was reduced thereafter
to 23% of that of the Parkland formula. The vitamin C group
(n = 6) received RL with vitamin C (14 mg/kg/hr), and the
control group (n = 6) received RE only. The 24-hour fluid
intake for each group was 32.5% of the Parkland formula
volume. Burn wound edema in the vitamin C group was significantly
less than that in the control group. The vitamin C group
maintained adequate hemodynamic stability as determined
with hematocrit and cardiac output values, but the control
group did not. Even though the initiation of the vitamin
C administration is delayed until 2 hours after burn, the
hourly infusion rate of the resuscitation fluid can be reduced
to 25% once it is started. Thus antioxidant therapy with
adjuvant vitamin C administration may be applicable to the
clinical setting in which a patient with burns arrives at
the burn care facility a few hours after the burn injury
occurred.
Vitamin C and pressure sores
Journal of Dermatological Treatment (United Kingdom), 1995,
6/3
This review describes 50 years of studies on the relationship
between vitamin C and wound healing. Several early studies
in animals reported a clear link between vitamin C depletion
and impaired wound healing, shown later to be due to an
effect on collagen synthesis. Further clinical studies found
that supplementary vitamin C improves wound healing even
in apparently vitamin C-replete individuals. Associations
between vitamin C and pressure sore development, and healing
of pre-existing pressure sores have been described, suggesting
a therapeutic role for vitamin C supplementation. However,
this would be complementary to current nursing and skin
care strategies in patients with, or at risk of developing,
pressure sores, such as those elderly patients admitted
with femoral neck fractures, or paraplegic subjects.
Vitamin C reduces ischemia-reperfusion injury in a rat
epigastric island skin flap model
ANN. PLAST. SURG. (USA), 1994, 33/6 (620-623)
Free radicals have been implicated in the cause of ischemia-reperfusion
injury. Various agents have been used in an attempt to reduce
ischemia-reperfusion injury pharmacologically, including
free radical scavengers. Vitamin C (ascorbic acid), a well-known
free radical scavenger, has not, to the best of our knowledge,
been evaluated in this respect. Previous work at our institution
has shown that vitamin C decreases capillary permeability,
thus significantly reducing fluid resuscitation requirements
in postburn cases. Because this is due in part to the scavenging
effect of vitamin C on free radicals, we investigated the
role, if any, of vitamin C on ischemia-reperfusion injury
in a rat epigastric island skin flap model. Twenty-four
adult Sprague-Dawley rats were divided into control and
vitamin C groups. Superficial epigastric island skin flaps
measuring 6.0 x 3.5 cm were raised. Pedicles were isolated
and occluded with microvascular clamps for 6 hours. The
flaps were then sutured back to their beds over Steri-Drape
barriers. Fifteen minutes before reperfusion, the control
group flaps were perfused via femoral artery cannulation
with normal saline (2.5 ml/kg). The vitamin C- treated group
was perfused in a similar fashion with 2.5 ml/kg of a vitamin
C/normal saline solution (27 mg/ml). The animals were observed
for 7 days, and the percentage of flap survival was determined
using a paper template technique. The vitamin C-treated
group demonstrated a significantly higher percentage of
flap survival than did the control group (25.8% mean vs.
7.5% mean, p < 0.025). In this animal model, vitamin
C reduced or limited reperfusion injury after 6 hours of
ischemia. Its presumed mechanisms of free radical reduction
and its relative safety make vitamin C a promising area
of investigation in future animal studies as well as in
human studies examining reperfusion injury.
An experimental study on the protection against reperfusion
myocardial ischemia by using large doses of vitamin C
CHIN. J. CARDIOL. (China), 1994, 22/1 (52-54+80)
To obtain the practical measure for the ischemia-reperfusion
injury, we developed an open chest pig model (occlusion
for 1 hour and reperfusion for 2 hours). Vitamin C (Vit
C 0.2 g/kg) was intravenously given within five minutes
to 8 pigs and 12 pigs received only saline as control. The
results showed that there were no differences in the hemodynamic
parameters, but the release of the creatine kinase isoenzyme
after the reperfusion was significantly decreased in the
vit C group (P < 0.05-0.01), and the ratio of the infarct
area and the risk area was 30.2% in the vit C group and
49.2% in controls respectively (P < 0.05). Furthermore,
the content of myocardial malondialdehyde was significantly
decreased in the vit C group. In order to observe the protective
effect of vitamin C we also developed an open chest rabbit
model. After four-hour reperfusion, vit C group had less
severe bleeding and milder damage to the capillary endothelium
than that of control group. On the rabbit model, the myocardial
free radicals were directly measured with the electron resonance
spectrograph after one half hour reperfusion (P < 0.05).
It was found that the free radical content was significantly
elevated in the control group (P < 0.05), vit C could
inhibit such elevation (P < 0.01). So it was evident
that the protection of vit C was directly related to scavenging
the free radicals.
Vitamins as radioprotectors in vivo. I. Protection by vitamin
C against internal radionuclides in mouse testes: Implications
to the mechanism of damage caused by the auger effect
USA RADIAT. RES. (USA), 1994, 137/3 (394-399)
The potential of vitamin C, an antioxidant, to protect
the radiosensitive spermatogonial cells in mouse testes
against the effects of chronic irradiation by radionuclides
incorporated into tissue was investigated. Interestingly,
when injected intratesticularly, a small and nontoxic amount
of vitamin C (1.5 microg in 3 microl saline) protected the
spermatogonia against the damage associated with high-LET
radiation caused by Auger electrons from similarly administered
5-(125I)-iodo-2'-deoxyuridine (125IdU). A dose modification
factor (DMF) of 2.3 was obtained. In contrast, no protection
was observed when 210Po, an alpha-particle emitter, was
administered similarly. These findings suggest that the
mechanism of action of the Auger effect is of an indirect
nature, which is in contrast to the direct action generally
believed to be responsible for biological damage caused
by high-LET radiations.
Experimental studies on the treatment of frostbite in rats
INDIAN J. MED. RES. SECT. B BIOMED. RES. OTHER THAN INFECT.
DIS. (India), 1993, 98/AUG. (178-184)
The effect of treatment by high dose of vitamin C, rapid
rewarming by 37degreeC water alone and with vitamin C, rapid
rewarming by 37degreeC decoction of Indian black tea alone
and with vitamin C for experimentally produced frostbite
was evaluated in 6 groups (25 each) of rats. Frostbite was
produced experimentally in the hind limbs by exposing the
animals at -15degreeC for 1h using the harness technique.
The degree of injury was assessed and classified on the
basis of tissue necrosis at the end of 15 days. Administration
of high dose of vitamin C for prolonged period and rapid
rewarming at 37degreeC water bath immediately after cold
exposure apparently reduced the tissue damage. High dose
of vitamin C therapy preceded by rapid rewarming in plain
water showed additional benefit. Rapid rewarming in decoction
of Indian tea resulted in identical beneficial effect. The
degree of tissue preservation was highest with rapid rewarming
in tea decoction followed by high dose of vitamin C.
The effects of high-dose vitamin C therapy on postburn
lipid peroxidation
USA J. BURN CARE REHABIL. (USA), 1993, 14/6 (624-629)
The effects of vitamin C treatment (14 mg/kg/hr) on postburn
lipid peroxidation were evaluated in 12 dogs. A lymph duct
above the ankle was cannulated bilaterally. Hourly lymph
flow rates, plasma and lymph total protein concentrations,
and plasma and lymph malondialdehyde concentrations were
measured before the burn injury and for 24 hours after the
burn injury. Four groups were employed: nonburn without
treatment, nonburn with vitamin C treatment, burn without
treatment, and burn with vitamin C treatment. The nonburn
groups showed no significant differences in lymph flow rates,
total protein flux, or lymph malondialdehyde level. In the
burn groups the postburn hourly lymph flow rate increased
by 850% without treatment and by 500% with vitamin C treatment,
whereas the postburn hourly total protein flux increased
by fiftyfold and twentyfold, respectively. There was a significant
reduction in the postburn lymph malondialdehyde level in
the group treated with vitamin C as compared with the nontreatment
group. We conclude that high-dose vitamin C administration
diminishes early postburn lipid peroxidation and reduces
microvascular leakage of fluid and protein.
Vitamin C as a radioprotector against iodine-131 in vivo
J. NUCL. MED. (USA), 1993, 34/4 (637-640)
The capacity of vitamin C (ascorbic acid) to mitigate radiation
damage resulting from the tissue-incorporated radionuclide
131I is examined. Spermatogenesis in mice is the experimental
model and spermhead survival is the biological endpoint.
When a small nontoxic amount of vitamin C was injected,
followed by a similar injection of 131I, the 37% spermhead
survival dose (D37) increased by a factor of 2.2 compared
with the D37 in animals receiving only the radionuclide.
Similar radioprotection was also observed when the animals
were maintained on a diet enriched with 1% vitamin C (by
weight). These results suggest that vitamin C may play an
important role as a radioprotector against accidental or
medical radiation exposures, especially when radionuclides
are incorporated in the body and deliver the dose in a chronic
fashion.
Effects of high-dose vitamin C administration on postburn
microvascular fluid and protein flux
REHABIL. (USA), 1992, 13/5 (560-566)
The effects of vitamin C treatment (14 mg/kg/hr) on burn
injury were evaluated in the hind paws of 12 mongrel dogs.
A lymph duct above one hind paw of each dog was cannulated.
Hourly lymph flow rates (QL) and plasma and lymph total
protein concentrations were measured before the burn injury
and for 6 hours after the burn injury. Data from 24 paws
were divided into four groups: nonburn without treatment,
nonburn with treatment, burn without treatment, and burn
with treatment. The nonburn groups showed no significant
differences in QL or in total protein flux. In the burn
groups the postburn hourly QL increased by sevenfold in
the nontreatment group and only by threefold in the treatment
group, whereas the postburn hourly total protein flux increased
by fifteenfold and fivefold, respectively. We conclude that
administration of high-dose vitamin C reduces early postburn
microvascular leakage of fluid and protein.
Ascorbate treatment prevents accumulation of phagosomes
in RPE in light damage
INVEST. OPHTHALMOL. VISUAL SCI. (USA), 1992, 33/10 (2814-2821)
In dark-reared albino rats, exposure to 2 or 3 hr of intense
light interrupted by 2 hr dark periods resulted in extensive
degeneration of photoreceptor cells and degeneration of
the retinal pigment epithelium (RPE). Ascorbate (ie, vitamin
C) administration prior to light exposure protected photoreceptors
and the RPE from light damage. In the present study, ascorbate-treated
and untreated rats were exposed to various cycles of intermittent
light. Immediately after this light exposure, phagosome
frequency in the RPE was morphologically evaluated in comparable
50 microm sections. In untreated rats, exposure to 2 or
3 hr of intermittent light resulted in a five- to sixfold
increase in phagosome density compared to unexposed controls.
In contrast, no increase in phagosome density was observed
in ascorbate-treated rats. In these animals, under all lighting
regimens, phagosome levels remained essentially identical
to those in rats not exposed to light. After a single nondamaging
light exposure, phagosome density remained at the level
of dark controls in ascorbate-treated and untreated rats.
These results indicate that phagosome frequency may serve
as an index for light damage and that the protective effect
of ascorbate may be linked to its capacity to prevent rod
outer segment shedding and phagocytosis under intense light
conditions.
Topical vitamin C protects porcine skin from ultraviolet
radiation-induced damage
BR. J. DERMATOL. (United Kingdom), 1992, 127/3 (247-253)
Ultraviolet radiation damage to the skin is due, in part,
to the generation of reactive oxygen species. Vitamin C
(L-ascorbic acid) functions as a biological co-factor and
antioxidant due to its reducing properties. Topical application
of vitamin C has been shown to elevate significantly cutaneous
levels of this vitamin in pigs, and this correlates with
protection of the skin from UVB damage as measured by erythema
and sunburn cell formation. This protection is biological
and due to the reducing properties of the molecule. Further,
we provide evidence that the vitamin C levels of the skin
can be severely depleted after UV irradiation, which would
lower this organ's innate protective mechanism as well as
leaving it at risk of impaired healing after photoinduced
damage. In addition, vitamin C protects porcine skin from
UVA-mediated phototoxic reactions (PUVA) and therefore shows
promise as a broad-spectrum photoprotectant.
The synergism of gamma-interferon and tumor necrosis factor
in whole body hyperthermia with vitamin C to control toxicity
MED. HYPOTHESES (United Kingdom), 1992, 38/3 (257-258)
In a previous paper, the synergism of gamma-interferon
and tumor necrosis factor was considered with whole body
hyperthermia. Because of the toxic effect of TNF due to
oxygen radicals, it is suggested that vitamin C be added.
Vitamin C supplementation in the patient with burns and
renal failure
J. BURN CARE REHABIL. (USA), 1992, 13/3 (378-380)
Vitamin C supplementation is an important component of
nutritional management in patients with burns. To supply
appropriate vitamin C therapy, complications such as renal
failure must be considered. An understanding of current
vitamin regimens and potential metabolic sequelae can assist
the practitioner in providing safe and therapeutic vitamin
C doses.
High-dose vitamin C therapy for extensive deep dermal burns
USA BURNS (United Kingdom), 1992, 18/2 (127-131)
We studied the haemodynamic effects of antioxidant therapy
with high-dose vitamin C administration (170 mg/kg/24h)
in guinea-pigs with 70 per cent body surface area deep dermal
burns. The animals were divided into three groups of six
animals each. Group 1 was resuscitated with Ringer's lactate
solution according to the Parkland formula; group 2 With
25 per cent of the Parkland formula with vitamin C; and
group 3 with 25 per cent of the Parkland formula without
vitamin C. There were no significant differences in heart
rates or in blood pressures between the groups throughout
the 24-h study period. Group 3 showed significantly higher
haematocrit values at 3 h postburn and thereafter as compared
with those of group 2. The cardiac output values of group
2 were significantly higher than those of group 3, but equivalent
to those of group 1. The water content of the burned skin
in group 2 was significantly lower than that in the other
groups, indicating that increased postburn capillary permeability
was minimized by the administration of vitamin C. With adjuvant
high-dose vitamin C administration, we were able to reduce
the 24-h resuscitation fluid volume from 4 ml/kg/per cent
burn to 1 ml/kg/per cent burn, while maintaining adequate
cardiac output.
Metabolic and immune effects of enteral ascorbic acid after
burn trauma
BURNS (United Kingdom), 1992, 18/2 (92-97)
A burned guinea-pig model (30 per cent BSA) was used to
study the effect of vitamin C on immune and metabolic responses
following burn trauma. Thirty-six guinea-pigs received identical
enteral diets (175 kcal/kg) except for the amount of vitamin
C. Groups I, II, III and IV were given formulae delivering
no vitamin C (1 RDA) 15 mg/kg/day 75 mg/kg/day or 375 mg/kg/day
respectively. Resistance to infection was evaluated by injecting
each animal with 0.1 ml of 1 x 109 Staph. aureus 502A subcutaneously
on day 10. On day 14, Staph. aureus abscesses were excised
and the numbers of viable colonies were determined. Results
showed no statistical differences between groups in the
clearance of Staph. aureus. From days 2 to 12, animals in
groups I, II and III had body weights of approximately 97
per cent of preburn body weight. Animals in group IV however,
had a body weight gain, 102 per cent of preburn body weight
on day 12. Animals in group IV also had significantly lower
metabolic rates on day 12 as compared to the animals in
the other groups. These results suggest that large amounts
of vitamin C have beneficial effects on the maintenance
of body weight and metabolic rate following burn trauma.
Reduced fluid volume requirement for resuscitation of third-degree
burns with high-dose vitamin C
J. BURN CARE REHABIL. (USA), 1991, 12/6 (525-532)
The effects of high-dose vitamin C therapy (170 mg, 340
mg, and 680 mg/kg/day) were evaluated in 70% body surface
area third-degree burns in guinea pigs that were resuscitated
with 1 ml/kg/%burn Ringer's lactate solution. The water
content measurements of the burned skin at 24 hours after
burn injury in the vitamin C-treated groups were significantly
lower than those of the control group (1 ml/kg/%burn) and
those of the standard resuscitation group (4 ml/kg/%burn).
The cardiac outputs in the group that received 340 mg vitamin
C were significantly higher than those of the control group
but not significantly different than those of the standard
therapy group at 2 hours after burn injury and thereafter.
In comparison with the regimen of 340 mg vitamin C, the
regimen of 680 mg vitamin C was no more beneficial, and
the regimen of 170 mg was less effective. With administration
of adjuvant high-dose vitamin C, we were able to reduce
the total 24-hour resuscitation volume from 4 ml/kg/%burn
to 1 ml/kg/%burn, while a comparable cardiac output was
maintained.
Nutritional considerations for the burned patient
SURG. CLIN. NORTH AM. (USA), 1987, 67/2 (109-131)
The metabolic response to injury is one of marked catabolic
hormonal predominance resulting in hypermetabolism and protein
wasting. Energy expenditure increases with increasing severity
of injury, but reaches a maximum of twice resting energy
expenditure when 50 percent TBSA is burned. We agree with
the nutritional recommendations of the group at the Boston
Shriner's Burn Institute and the Massachusetts General Hospital.
These include providing calories at twice the resting energy
expenditure, as predicted by the Harris-Benedict equations,
for patients with greater than 30 percent BSAB; protein
is provided at 2.5 gm per kg per day based on ideal body
weight. It is important to recognize that these are optimal
goals, but their attainment must be governed by safety considerations
for the patient. It is probably safe to supplement intake
with a multivitamin and vitamin C, as well as zinc, but
our understanding of micronutrient therapy for stressed
patients is rudimentary.
Ascorbic acid metabolism in trauma
INDIAN J. MED. RES. (INDIA), 1982, 75/5 (748-751)
In major trauma such as severe head injury, burns or lacerated
injury, there was a precipitous fall in plasma ascorbic
acid level accompanied by a significant rise in blood dehydroascorbate
level. However, this change was temporary and normal vitamin
C status was regained after recovery from the stress condition.
A similar alteration in plasma ascorbate level was also
found after major surgery. This alteration in ascorbic acid
status was not due to lack of reduction of dehydroascorbic
acid to ascorbic acid but due to a high turnover of ascorbic
acid in trauma. Supplementation of ascorbic acid in trauma
resulted in a temporary increase in the plasma ascorbic
acid level.
Determination of ascorbic acid in human vitreous humor
by high-performance liquid chromatography with UV detection
Current Eye Research (United Kingdom), 1997, 16/6 (589-594)
Purpose. Ascorbic acid (AA) accumulates in vitreous at
a concentration several times higher than in plasma. It
has been suggested that AA may serve as an antioxidant that
protects ocular tissues from free radical attack. There
are many reports about the concentration of AA in ocular
tissues. However, AA in adult human vitreous humor has not
been determined. We measured concentrations of AA from pathologic
human vitreous samples and compared the results.
Methods. AA was measured by high-performance liquid chromatography
(HPLC) with UV detection. Human vitreous humor was collected
from patients undergoing pars plana vitrectomy.
Results. AA was quantified in vitreous humor of proliferative
diabetic retinopathy (PDR), proliferative vitreoretinopathy
(PVR), macular hole (MH), idiopathic premacular fibrosis
(PMF), and Terson syndrome (Terson). The concentrations
of AA were 120.9 plus or minus 36.3 microg/ml (mean plus
or minus SD), 129.8 plus or minus 36.6, 311.5 plus or minus
126.7, 446.9 plus or minus 154.2 and 406.0 plus or minus
22.0, respectively. There was no significant difference
between the PDR and the PVR groups (unpaired t-test). Patients
with PDR and PVR showed significantly lower concentrations
of AA than those with MH.
Conclusions. These findings suggest that increased oxidative
stress may be produced in the ocular tissues of eyes with
PDR and PVR, and AA appears to be consumed (oxidized) in
performing its protective role.
Erythrocyte and plasma antioxidant
Presse Medicale (France), 1996, 25/5 (188-192)
Objectives: Some biologic parameters involved in cell defence
against oxygen radicals (plasmatic vitamins C and E, erythrocyte
glutathione peroxidase, glutathione reductase and superoxide
dismutase) were measured in single blood samples from 119
diabetic infants, adolescents and young adults.
Methods: Data were studied in relation to residual insulin
secretion determined by C peptide, level of metabolic control
appreciated by glycosylated haemoglobin, lipid abnormalities
and subclinical complications (retinopathy, neuropathy and
nephropathy).
Results: There was no change in antioxidant parameters
with insulin secretion. Patients with poor glycaemic control
and high plasma lipids had higher levels of plasma vitamin
E. Patients with nephropathy had lower plasma vitamin C
levels and those with neuropathy showed lower erythrocyte
glutathione peroxidase activity. Plasma vitamin C concentrations
and erythrocyte glutathione reductase activities were negatively
correlated with the age of the patients and the duration
of the disease.
Conclusion: Higher transport capacity of vitamin E probably
explains the elevated levels of vitamin E observed in patients
with high lipid levels and long lasting illness. The lower
levels of vitamin C in the presence of nephropathy may be
due to an increased renal excretion of this vitamin. The
reduction of glutathione peroxidase, glutathione reductase
activities and vitamin C levels confirms the existence of
an oxidative stress in type 1 diabetes.
The regional distribution of vitamins E and C in mature
and premature human retinas
INVEST. OPHTHALMOL. VISUAL SCI. (USA), 1988, 29/1 (22-26)
Vitamin E is used to ameliorate retinopathy of prematurity,
but little is known about baseline vitamin E levels in retinas
of premature infants or the effect of vitamin E supplementation
on these levels. Vitamin E and C levels were measured in
mature retinas (1 month to 73 years) and in retinas of premature
infants (22 to 33 weeks of gestation). The infants fell
into two groups: (1) those who survived <12 hr and received
no vitamin E, and (2) those who survived 4 days and received
vitamin E supplementation. Premature infants are born with
5 to 12 percent the vitamin E levels found in mature retinas.
Vitamin E levels in vascular and avascular retina of premature
infants increased with gestation. Infants born 27 weeks
gestation and surviving at least 4 days with vitamin E supplementation
demonstrated markedly elevated vitamin E levels in vascular
and avascular retina when compared to supplemented infants
<27 weeks gestation. Premature infants possessed 35-50%
higher levels of retinal vitamin C than those found in mature
retinas. These data demonstrate that premature infants are
born with relatively low levels of retinal vitamin E, particularly
in the avascular region, but contain an abundance of retinal
vitamin C. These data further suggest that vitamin E supplementation
results in a rapid increase in retinal vitamin E levels,
particularly in infants 27 weeks gestational age.
Effects of dietary vitamin C and E supplementation on the
copper mediated oxidation of HDL and on HDL mediated cholesterol
efflux.
Rifici VA; Khachadurian AK
Department of Medicine, Robert Wood Johnson Medical School,
University of Medicine and Dentistry of New Jersey, New
Brunswick 08903-0019, USA. Atherosclerosis (IRELAND) Nov
15 1996, 127 (1) p19-26
Copper mediated oxidative modification of high density
lipoprotein (HDL) diminishes its capacity to promote cholesterol
efflux from cells in culture. In the present study, HDL
was isolated from eight subjects before and after a 10 day
administration of the antioxidant vitamins C and E. After
incubation HDL (1.25 mg protein/ml) with 10 microM copper
for 0-4 h or with 0-20 microM copper for 4 h, thiobarbituric
acid reactive substances (TBARS) production was significantly
decreased following vitamin administration suggesting that
the vitamins decreased the susceptibility of HDL to oxidation.
However, two other assays of lipoprotein oxidation, trinitrobenzene
sulfonic acid reactivity and conjugated diene formation,
did not show a consistent effect of vitamin administration.
To study cholesterol efflux, J774 macrophages were labeled
with 3H cholesterol (0.1 microCi/ml, 50 micrograms/ml) and
incubated with HDL or oxidized HDL (100 micrograms protein/ml)
for 24 h. HDL isolated before vitamins and oxidized in vitro
was 39% less effective in mediating efflux compared to unmodified
HDL, while HDL isolated after vitamins and oxidized was
22% less effective (before vs. after vitamins, P < 0.015).
HDL oxidation determined by measuring TBARS production correlated
with decreased cholesterol efflux (r = 0.37, P < 0.050).
These data suggest that oxidation of HDL interferes with
its role in reverse cholesterol transport and that antioxidant
vitamins have a protective effect.
Possible prevention of postangioplasty restenosis by ascorbic
acid.
Tomoda H; Yoshitake M; Morimoto K; Aoki N
Department of Cardiology, Tokai University, Kanagawa, Japan.
Am J Cardiol (UNITED STATES) Dec 1 1996, 78 (11) p1284-6
In this preliminary study to assess the possibility of
using ascorbic acid to prevent post-percutaneous transluminal
coronary angiography (PTCA) restenosis, the incidence of
restenosis was significantly less in 50 patients receiving
500 mg/day of oral ascorbic acid than idant, appeared to
be possibly effective in attenuating post-PTCA restenosis.
Effectiveness of antioxidants (vitamin C and E) with and
without sunscreens as topical photoprotectants.
Darr D; Dunston S; Faust H; Pinnell S
North Carolina Biotechnology Center, Raleigh, N.C., USA.
Acta Derm Venereol (NORWAY) Jul 1996, 76 (4) p264-8,
Considerable interest has been recently generated concerning
the use of natural compounds, anti-oxidants in particular,
in photoprotection. Two of the best known anti-oxidants
are vitamins C and E, both of which have been shown to be
somewhat effective in different models of photodamage. Very
little has been reported, however, on the effectiveness
of a combination of the two (known to be biologically the
more relevant situation); nor have there been detailed studies
on the ability of these antioxidants to augment commercial
sunscreen protection against UV damage. We report that (in
swine skin) vitamin C is capable of additive protection
against acute UVB damage (sunburn cell formation) when combined
with a UVB sunscreen. A combination of both vitamins E and
C provided very good protection from a UVB insult, the bulk
of the protection attributable to vitamin E. However, vitamin
C is significantly better than vitamin E at protecting against
a UVA-mediated phototoxic insult in this animal model, while
the combination is only slightly more effective than vitamin
C alone. When vitamin C or a combination of vitamin C and
E is formulated with a commercial UVA sunscreen (oxybenzone),
an apparently greater than additive protection is noted
against the phototoxic damage. These results confirm the
utility of anti-oxidants as photoprotectants but suggest
the importance of combining the compounds with known sunscreens
to maximize photoprotection.
Prevention of dopamine-induced cell death by thiol antioxidants:
possible implications for treatment of Parkinson's disease.
Offen D; Ziv I; Sternin H; Melamed E; Hochman A. Department
of Neurology, Beilinson Medical Center, Petah-Tiqva, Israel.
Exp Neurol (UNITED STATES) Sep 1996, 141 (1) p32-9
We have recently shown that dopamine (DA) can trigger apoptosis,
an active program of cellular self-destruction, in various
neuronal cultures and proposed that inappropriate activation
of apoptosis by DA and or its oxidation products may initiate
nigral cell loss in Parkinson's disease (PD). Since DA toxicity
may be mediated via generation of oxygen-free radical species,
we examined whether DA-induced cell death in PC12 cells
may be inhibited by antioxidants. We have found that the
thiol containing compounds, reduced glutathione (GSH), N-acetyl-cysteine
(NAC), and dithiothreitol (DTT) were markedly protective,
while vitamins C and E had lesser or no effect. The thiol
antioxidants and vitamin C but not vitamin E, prevented
dopamine autooxidation and production of dopamine-melanin.
Their protective effect has also manifested by inhibiting
DA-induced apoptosis; DNA fragmentation was prevented as
was shown histochemically by the in situ end-labeled DNA
technique (TUNEL). Intracellular GSH and other thiols constitute
an important natural defense against oxidative stress. We
have found that depletion of cellular GSH by the addition
of phoron, a substrate of glutathione transferase, and buthionine
sulfoximine (BSO), an inhibitor of gamma-glutamyl transpeptidase,
significantly enhanced DA toxicity. Cotreatment with NAC
rescued the cells from the toxic effect of BSO+DA, and phoron+
DA, while addition of GSH provided only partial protection
from BSO+DA toxicity. Our data indicate that the thiol family
antioxidants, but not vitamins C and E, are highly effective
in rescuing cells from DA-induced apoptosis. Further study
of the mechanisms underlying the unique protective capacity
of thiol antioxidants may lead to the development of new
neuroprotective therapeutic strategies for PD.
Vitamin C intake and cardiovascular disease risk factors
in persons with non-insulin-dependent diabetes mellitus.
From the Insulin Resistance Atherosclerosis Study and the
San Luis Valley Diabetes Study.
Mayer-Davis EJ; Monaco JH; Marshall JA; Rushing J; Juhaeri
Department of Public Health Sciences, Bowman Gray School
of Medicine, Wake Forest University, Winston-Salem, North
Carolina 27157-1063, USA. Prev Med (UNITED STATES) May-Jun
1997, 26 (3) p277-83
BACKGROUND: Persons with non-insulin-dependent diabetes
mellitus (NIDDM) are at increased risk for cardiovascular
disease, partly due to concomitant worsening of traditional
risk factors including dyslipidemia and hypertension. Based
on evidence from small, controlled clinical trials, we hypothesized
that increased intake of vitamin C would be associated with
improved cardiovascular disease (CVD) risk factor status
among community-dwelling persons with NIDDM.
METHODS: In separate but parallel statistical analyses,
hypotheses were evaluated among persons with NIDDM confirmed
by WHO criteria from the Insulin Resistance Atherosclerosis
Study (IRAS, n = 520) and from the San Luis Valley Diabetes
Study (SLVDS, n = 422). For IRAS, diet and vitamin supplement
use was assessed by food frequency interview and for SLVDS,
by 24-hr dietary recall interview.
RESULTS: Mean vitamin C intake (mg/day) was 275 for IRAS
and 133 for SLVDS, including supplements. In cross-sectional
regression models from each data set, vitamin C intake was
not associated with systolic or diastolic blood pressure
nor with HDL-C, LDL-C, or triglycerides (P values 0.10;
adjusted for calories, demographic and lifestyle variables,
obesity, diabetes duration, and medications). In prospective
analyses including 285 SLVDS participants, baseline vitamin
C intake was not related to any of these CVD risk factors
measured an average of 4 years later nor to change in CVD
risk factor status during the follow-up period.
CONCLUSIONS: We conclude that, across a wide range of intake,
vitamin C does not appear to be associated with improved
CVD risk factor status among community-dwelling persons
with diabetes.
Vitamin C and cardiovascular disease: a systematic review.
Ness AR; Powles JW; Khaw KT. Institute of Public Health,
University Forvie Site, Cambridge, UK. J Cardiovasc Risk
(ENGLAND) Dec 1996, 3 (6) p513-21
BACKGROUND: Laboratory studies suggest that antioxidants,
such as Vitamin C, are important inhibitors of atherosclerotic
lesions. Most epidemiological reviews have considered all
antioxidants together. This review seeks to clarify the
current state of knowledge specifically concerned with vitamin
C.
METHODS: All ecological studies, case-control studies,
prospective studies and trials in humans that examined the
association between vitamin C intake or blood levels of
vitamin C and cardiovascular disease were included. Relevant
references were located search for articles published from
1966 to 1996, by an EMBASE search for articles published
from 1980 to 1996, by searching personal bibliographies,
books and reviews and from citations in located articles.
RESULTS: For coronary heart disease four of seven ecological
studies, one of four case-control studies and three of 12
cohort studies found a significant protective association
with vitamin C intake or status. For strokes two of two
ecological studies, none of one case-control study and two
of seven cohort studies found a significant protective association.
For total circulatory disease, two of three cohort studies
reported a significant protective association.
CONCLUSIONS: The evidence, albeit limited, is consistent
with vitamin C having protective effect against stroke whereas
the evidence that vitamin C is protective against coronary
heart disease is less consistent. The lack of an association
for coronary heart disease could be explained in terms of
there being a true lack of effect, dietary measurement error,
a threshold effect, and effect of seasonal variations in
intake, an interaction with other dietary constituents or
a relatively short duration of follow-up.
