| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Surgery, University of Medicine and Dentistry of New Jersey, School of Osteopathic Medicine, Stratford, New Jersey 08084
 |
ABSTRACT |
|---|
 TOP
 ABSTRACT
 INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
The objectives of this study were to assess oxidant
damage during and after spaceflight and to compare the results against bed rest with 6° head-down tilt. We measured the urinary excretion of the F2 isoprostane, 8-iso-prostaglandin (PG)
F2
, and 8-oxo-7,8-dihydro-2 deoxyguanosine (8-OH DG)
before, during, and after long-duration spaceflight (4-9 mo) on
the Russian space station MIR, short-duration spaceflight on the
shuttle, and 17 days of bed rest. Sample collections on MIR were
obtained between 88 and 186 days in orbit. 8-iso-PGF2 and 8-OH DG are markers for oxidative damage to membrane lipids and
DNA, respectively. Data are mean ± SE. On MIR, isoprostane levels
were decreased inflight (96.9 ± 11.6 vs. 76.7 ± 14.9 ng · kg
1 · day1,
P < 0.05, n = 6) due to decreased dietary intake
secondary to impaired thermoregulation. Isoprostane excretion was
increased postflight (245.7 ± 55.8 ng · kg1 · day1,
P < 0.01). 8-OH DG excretion was unchanged with spaceflight and increased postflight (269 ± 84 vs 442 ± 180 ng · kg1 · day1,
P < 0.05). On the shuttle, 8-OH DG excretion was
unchanged in- and postflight, but 8-iso-PGF2 excretion
was decreased inflight (15.6 ± 4.3 vs 8.0 ± 2.7 ng · kg1 · day1,
P < 0.05). No changes were found with bed rest, but
8-iso-PGF2 was increased during the recovery phase (48.9 ± 23.0 vs 65.4 ± 28.3 ng · kg1 · day1,
P < 0.05). The changes in isoprostane production were
attributed to decreased production of oxygen radicals from the electron
transport chain due to the reduced energy intake inflight. The
postflight increases in the excretion of the products of oxidative
damage were attributed to a combination of an increase in metabolic
activity and the loss of some host antioxidant defenses inflight. We
conclude that 1) oxidative damage was decreased inflight, and
2) oxidative damage was increased postflight.
isoprostanes; 8-hydroxydeoxyguanosine
| |
INTRODUCTION |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
THERE ARE A NUMBER OF REASONS for suspecting that oxidative stress may be increased with spaceflight. There is an increase in the exposure to high-energy radiation because of the absence of the protective effects of the earth's atmosphere, with the resultant generation of high-energy free radicals (25). Other possible causes for increased free-radical generation are altered oxygen metabolism from perturbed gas exchange within the lungs (38), or a change in intermediary metabolism. The Skylab investigators suggested that a possible reason for an apparent increase in energy expenditure during spaceflight was an uncoupling of oxidative phosphorylation (28). A similar suggestion was made by Burakhova and Mailyan after examining the electron transport system in rat skeletal muscle after 3 wk in space (3). The body generates ~5 g of reactive oxygen species per day, mostly by leakage from the electron transport chain during oxidative phosphorylation (12).
Until recently, the quantification of oxidative stress has been
difficult to assess in humans because of the lack of sensitive and
reliable assays. This problem now appears to have been solved by the
discovery of the F2 isoprostanes to assess free-radical lipid oxidation and the development of methods for the analysis of the
products of DNA oxidation, specifically 8-oxo-7,8-dihydro-2 deoxyguanosine (8-hydroxydeoxyguanosine, 8-OH DG) (20, 24, 29).
Isoprostanes are derived from arachidonic acid containing phospholipids
by autooxidation, leading to a series of PGF2-like compounds. The bicylcoendoperoxide PG intermediates are reduced to four
regioisomers, each of which can comprise eight racemic diastereoisomers. These 64 isomers are collectively called the PGF2 isoprostanes [8-iso-prostaglandin (PG)
F2].
Like lipids, DNA is also susceptible to oxidative damage (1, 7, 27); in
fact, DNA is constantly being damaged and repaired in living cells. It
has been estimated that the damage rate is ~104
nucleotides · cell1 · day1
(20). The most abundant of the nucleotide oxidation products is
8-hydroxydeoxyguanosine. Once produced, 8-hydroxydeoxyguanosine is not
further degraded and is excreted in the urine without further metabolism (19). Measurements of urinary isoprostane and
8-hydroxydeoxyguanosine excretion have provided strong supporting
evidence for a role for oxidative damage in the pathogenesis of a wide
variety of human disorders, including atherosclerosis and cancer
(11, 20, 21, 24).
The primary objectives of this experiment were to assess oxidant stress
during and after long-duration spaceflight on the Russian space
station, MIR. To assess oxidative damage, we measured the urinary
excretion of 8-iso-PGF2 and 8-hydroxydeoxyguanosine. Together the two assays can provide an assessment of any oxidative damage incurred. To facilitate interpretation of the data from MIR, we
compared the MIR data against the results from a short-duration (17-day) shuttle mission and a 6° head-down tilt, bed- rest study.
| |
METHODS |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Informed consent forms were obtained in accordance with the policies of the United States National Aeronautics and Space Administration (NASA), the Russian Academy of Sciences Experiment Board, The Russian Space Agency (RSA), and the University of Medicine and Dentistry of New Jersey.
Long-Duration Flight on MIR
The subjects for this study were two astronauts (American) and four cosmonauts (Russian). Time in earth orbit varied with the subject; range was 4-9 mo.Pre- and postflight. The preflight measurements consisted of between two and four sessions during the year before the mission. Each session lasted 2 days. Twenty-four-hour pools were obtained on day 2, and for most sessions 24-h pools were also collected on day 1 of the session. The actual number of preflight sessions depended on crew availability. Sessions were conducted either at NASA facilities in the US (the Johnson and Kennedy Space Centers) or the RSA facility at Star City, near Moscow. During each of the two days, the subjects kept a detailed record of their dietary intake.
The American astronauts were launched and landed on the shuttle in Florida; however, before launch they lived in Russia, in RSA facilities in Star City. They were flown to Houston and the postflight studies were continued at the Johnson Space Center. The Russian cosmonauts returned on a Soyuz space vehicle and spent the first 2 wk postflight at Star City. The postflight studies followed the same protocol as the preflight, with sessions being either return (R)+0 and R+1, or R+1 and R+2, R+6 and R+7, and R+13 and R+14. On occasion, a session was displaced by a day due to a crew member's being unavailable. For the preflight period, each session entailed 2 days of dietary monitoring with 24-h urine collections on
1, but usually 2, days.
Inflight.
With two exceptions, a similar protocol to that of the
preflight and postflight periods was performed inflight. All of the inflight data were collected between 88 and 147 days of spaceflight [mean 147 ± 8 days (33)]. Briefly, the food was bar
coded, and the crew recorded the time and amount of food eaten.
Opportunities for collecting 24-h urines on MIR were limited because of
the need to conserve water; only one 24-h urine collection could be done at a time, because on MIR, urine water was recycled for future use. Inflight urine collections were done between 88 and 147 days after
launch. The urines were collected in specially designed plastic bags.
An aliquot was removed and put in a 10-ml syringe, which was placed in
the on-board 
20°C freezer. Samples were brought back to
earth on the shuttle supply missions and stored at 70°C until analyzed (details given in Ref. 33).
Diet analysis. The dietary records were analyzed by NASA personnel from the Nutrition and Metabolism Laboratory of the Johnson Space Center by use of the Nutritionist 2.8 program (University of Minnesota, St. Paul, MN), together with some data especially collected by NASA personnel on Russian foods.
Space Shuttle
The urine samples used for this study were collected on the 17-day Life and Microgravity mission (LMS), which was flown in the summer of 1996. Details of the mission and the sample collection are given in Ref. 34. Briefly, the subjects were the four payload crew members of the LMS mission. There were two overall goals of the mission. The first was to conduct a series of experiments on the response of the human musculoskeletal system to spaceflight, and the second was to perform a series of material science experiments. The samples analyzed for this experiment were the urines collected as part of the nitrogen and energy balance studies (34). Daily dietary intake was monitored, and daily urine collections were made for the period beginning 15 days before launch and ending 15 days after landing, as previously described (34). Samples were stored at16°C inflight, and after return to
earth they were transferred to a freezer at 70°C.
Bed Rest
A 17-day bed-rest study with 6° head-down tilt was conducted in the Clinical Research Center of the NASA-Ames Research Center with eight healthy adult males recruited from the local community. The objective of the bed-rest study was to compare bed rest and spaceflight, using the LMS mission as the flight study. Accordingly, the bed-rest study was designed to simulate the flight experiment as closely as possible. The bed-rest study included the full complement of exercise testing that was done on the shuttle payload (34).As with the flight study, the bed-rest study was divided into three
phases, a 15-day pre-bed-rest ambulatory period, followed by 17 days of
bed rest, and ending with a 15-day recovery period. During the 47 days
of the study, the subjects received all their food from the research
center. An attempt was made to provide the subjects with a
"controlled" ad libitum diet. Twelve daily menus were made up,
comprised of 2,500 kcal/day and 90 g protein/day. In addition, subjects
were allowed access to a snack basket containing fruit, cookies, some
candy, and granola bars. Details of the bed-rest study are given in
Refs. 31 and 34. Urine was collected continuously for the 47-day period
and kept frozen at 70°C until analyzed.
Analytical methodology. In some cases where a 24-h pool was missing from the MIR studies, the missing pool was supplied by NASA as part of a sample-sharing agreement between investigators. Most of the urinary creatinine values for the MIR studies were supplied by NASA; the remainder were measured by us using the picric acid method with a kit marketed by Sigma-Aldrich (St. Louis, MO). The 24-h pools for the LMS mission were available from our previous experiments (31, 34). Accurate 24-h pools were not available for the bed-rest study because all urine voids were ad libitum; therefore, some of the potential "24"-h pools deviated quite significantly from 24 h, so either 48- or 72-h pools were made up by the fractional aliquot method. Where the number of periods was uneven (e.g., the bed-rest period was actually 17 days), the paired days were selected so that the 2-day exercise periods fell in the same pool (31).
Isoprostane analyses were done on unextracted urine (UN) and an organic extract of urine (EX), by use of an ELISA kit (Oxford Chemicals, Oxford, MI). The isoprostanes were extracted from the urine using the methodology recommended by the manufacturer. Urine (0.5-1 ml) was adjusted to pH 3.0 and loaded onto a C18 Sep-Pak (Waters, Milford, MA). After the sample was washed with water (10 ml), followed by heptane (10 ml), the isoprostanes were eluted with ethyl acetate (5 ml). Sodium sulfate (~1 g) was added, and the solution was applied to a silica Sep-Pak and the isoprostanes eluted with a 1:1 mixture of ethyl acetate and methanol. The solvent was removed with dry N2, and the residue was dissolved in a known volume of a dilution buffer supplied by the kit manufacturer and assayed by ELISA. For the MIR isoprostane samples, each sample (extracted or unextracted) was assayed at three different dilutions. For 8-OH DG we used the ELISA kit (Genox, Baltimore, MD). Each sample from MIR was assayed in triplicate at three dilutions. For financial reasons the LMS flight and bed-rest studies were analyzed only for 8-iso-PGF2 and
8-OH DG in duplicate at one dilution. We did not have enough urine to
do both extracted and unextracted isoprostane determinations on the LMS
flight experiment urines, so we did only the unextracted assays.
Statistics. Data were analyzed by a repeated-measures design ANOVA (RMANOVA). For consistency all data sets were divided into three time periods, preflight (pre-bed-rest), flight (bed rest), and postflight (recovery), and the natural logarithms of the data were used for the RMANOVA. Significance was accepted at P < 0.05. If the RMANOVA indicated significance at P < 0.05 or better, group differences were identified by the Student-Newman-Keuls test. To investigate whether there was any time dependence in the postflight (bed-rest) period, we used paired t-tests of a specific postflight (bed-rest) period against the mean preflight value. Significance was accepted at P < 0.01. The Sigmastat Statistical System (SPSS, Chicago, IL) was used for the statistical computations. Data in the text, figures, and tables are means ± SE.
| |
RESULTS |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Regarding MIR, we have previously described the changes in nutrition
and the accompanying weight changes for these astronauts before and
after spaceflight (33). Briefly, the average weight loss was 4.6 ± 1.1 kg (range 2.4-8.0 kg, Table 1).
Energy intake inflight was significantly less than either pre- or
postflight (22 ± 9%, P < 0.05, Table 1). Postflight energy
intake returned to, but was not increased over, the preflight levels.
Likewise, dietary intake of the anti-oxidant vitamins (A, C, E, and
selenium) were similar pre- and postflight (Table
2). We have no data on antioxidant intake
inflight (Table 2). The urinary excretion of 8-iso-PGF2
was decreased by 20% inflight (P < 0.05); 8-OH DG was
unchanged (Table 1).
|
|
The postflight data collection schedule called for three sessions of 2 days per session, beginning on R+0 or R+1, R+6 or R+7 and R+13 or R+14.
The sessions were combined to give a single data set for each subject.
Isoprostane levels were decreased inflight by ~20% and increased
postflight by 200% (Table 1, P < 0.01). These relationships
applied to both UN and EX and whether the results were expressed as per
kilogram body wt or normalized to creatinine (Table 1). There was no
change in 8-OH DG inflight, but as with 8-iso-PGF2, 8-OH
DG excretion was substantially increased postflight (Table 1, P < 0.05). Figure 1 shows the postflight
time course for 8-OH DG and 8-iso-PGF2. Excretion of
8-iso-PGF2 was substantially increased for the duration of the postflight measurement period.
|
As for the shuttle, the dietary data in Table
3 are for the days corresponding to the
urine samples analyzed, namely five samples from the week immediately
preceding launch, the five last samples from the flight period, and the
first five days after landing. Energy intake was decreased by 40%
inflight. As with MIR, postflight energy intake returned to, but was
not increased over, the preflight levels. No changes in 8-OH DG
inflight or postflight were found; however, isoprostane levels in
unextracted urine were decreased inflight by ~40% (Table 3,
P < 0.01). No changes postflight were observed, although the
error bars are much larger postflight than preflight (Fig.
2).
|
|
Energy intake was reduced by 10% during the bed-rest period (Table
4) (34). Excretion of 8-OH DG was unchanged
during and after bed rest. Excretion of 8-iso-PGF2
(extracted and unextracted) was unchanged during bed rest but was
increased during the recovery phase by ~30% (Table 4). Statistical
significance was found only with the data normalized to creatinine. As
with the other two studies, the SEs are much greater, particularly for
8-iso-PGF2 during the recovery phase (Fig.
3).
|
|
| |
DISCUSSION |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
The database. Although there was considerable negative publicity in the lay press about the problems encountered with the Shuttle-MIR program, these flights (MIR 21 and 23) were less problematic than some of the earlier or later flights (4). As described in our previous paper, although the amount of data obtained was not large, the quality of the data was good (33). The principal reasons for the limited data were that 1) one of the Russian crew members was switched preflight for medical reasons; 2) technical problems on MIR precluded any measurements during the first three months in orbit; and 3) crew availability for all three phases of the experiment was limited (4).
There were also limitations for the shuttle and bed-rest studies. For the shuttle, the amount of urine available was inadequate to permit assays for both extracted and unextracted 8-iso-PGF2 to
be done. We elected to do the unextracted assay because the urine
requirements were less. For both the shuttle and bed-rest analyses
there were also financial limitations.
The ELISA for 8-iso-PGF2 measures only one of several
possible isomers. Although the values from extracted and unextracted urines correlate with each other (r2 = 0.74, P < 0.01), the unextracted values with this kit are about three times greater than the extracted values. In the present study,
r = 3.4 ± 0.2. According to the manufacturer of the kits (Oxford Chemicals) only the extracted values correlate with those found
by mass spectroscopy. The values from UN are higher because of cross
reactivity from other immunoreactive isoprostanes. Because the
extracted method and the gas chromatography-mass spectometry methods
measure only one of the several possible 8-iso-PGF2 isomers, the unextracted data are useful in that they provide information showing that the increase in isoprostane production is not
limited to one specific isoprostane.
Some of the preflight and pre-bed-rest SEs for
8-iso-PGF2 and 8-OH DG appear to be rather large. This
was due to intersubject variability rather than to variability within
the assay. The intra-assay coefficients of variability for 8-OH DG were
4.6 ± 0.5% for MIR, 4.5 ± 0.3% for shuttle, and 2.5 ± 0.2% for
bed rest. For unextracted isoprostanes the corresponding values were
4.3 ± 0.4, 7.4 ± 0.6 and 11.0 ± 0.6%, respectively. Extracted
isoprostane assays were done only on MIR and the bed-rest subjects. The
coefficients of variation were 6.3 ± 0.7 and 7.6 ± 0.5%,
respectively. Intersubject variation was much greater (20-50%)
and accounts for the high SEs for the mean prestudy values in the
tables. If the data are normalized to percentage of the mean preflight
value, much of the variance in the preflight bed-rest period disappears
(Figs. 1-3).
Inspection of the preflight isoprostane data suggests that the three
groups of subjects (MIR, shuttle, and bed-rest) were different. One
astronaut on MIR had very high 8-OH DG and isoprostane levels.
Eliminating this subject from the preflight means gives 9.84 ± 1.89 (n = 5) ng · g
creatinine1 · day1
for 8-OH DG, 4.42 ± 0.71 ng · g
creatinine1 · day1
for unextracted isoprostane, and 1.65 ± 0.34 ng · g
creatinine1 · day1
for extracted isoprostane. The postflight differences between the
groups are still significant for either unextracted isoprostanes (P < 0.05, F = 7.55), extracted isoprostanes
(P < 0.05, F = 16.81), and 8-OH DG (P < 0.05, F = 5.46) as is the inflight decrease for unextracted
isoprostanes (P < 0.05, F = 16.81).
The differences most likely reflect those in the diets of the three
groups. The differences in preflight status are unlikely to be the
cause of the postflight increases in isoprostane excretion on MIR,
because a similar increase was found after bed rest. The bed-rest
subjects were on a metabolic balance study and thus on a constant diet
for the duration of the 47-day study period. For MIR, the two American
astronauts lived in Russia before launch from the US and they landed in
the US with all postflight measurements being made in the US. Some of
the samples for the preflight measurements on the two American crew
persons were collected while they were in Russia. The Russian crews ate
the food available at Star City, Russia, pre- and postflight.
To determine whether the results could have been skewed by the
differences between launch and landing procedures for astronauts and
cosmonauts, we examined the data of the four Russians separately. The
RMANOVA confirmed the overall postflight increases in 8-OH DG
(F = 8.39, P < 0.05), unextracted
8-iso-PGF2 (F = 9.81, P < 0.05), and
extracted 8-iso-PGF2 (F = 11.69, P < 0.05), but not the inflight decrease in isoprostane excretion. A small number of subjects precludes detecting any but the grossest differences.
Inflight.
On both MIR and the space shuttle, 8-iso-PGF2 was
decreased inflight (Tables 1 and 3). The decrease was found with both
EX and UN for MIR and for UN on the shuttle. With both missions, 8-OH
DG showed a weak trend toward an increase (Figs. 1 and 2). The two
conclusions that can be drawn with certainty from the inflight results
are 1) that the decreased isoprostane excretion on MIR is not
an artifact caused by possible environmental abnormalities on MIR,
because the same result was found on the space shuttle, and 2)
oxidative damage to lipid membranes was not increased during spaceflight. The discussion of the inflight data that follows is less
certain but is reasonable.
production could be
due to 1) increased quenching of free-radical chain reactions as a consequence of increased antioxidant intake, 2) increased production of endogenous antioxidants, or 3) decreased oxidant production and propagation. The first two are unlikely. Increased antioxidant intake inflight is improbable; dietary intake was decreased
during spaceflight (Tables 2 and 3), and there was no specific
requirement for the crew to take supplementary vitamins or antioxidants
above their preflight amounts (personal communication, Dr. S. Lucid).
An increase in endogenous antioxidant production is also unlikely. The
available evidence suggests that the MIR crew persons were in negative
energy balance. Lane et al. showed that energy expenditure inflight was
not different from that on the ground [35.2 ± 1.8 vs. 36.2 ± 5.8 kcal · kg1 · day1
(15)]. Our value for a mission with heavy exercise requirements was 40.8 ± 0.6 kcal · kg1 · day1
(34). Energy intake on both the MIR [26.9 ± 2.2 kcal · kg1 · day1
(33)] and LMS [24.6 ± 3.3 kcal · kg1 · day1
(34)] missions was substantially less than either of these two
values, and the differences are statistically significant (P < 0.05). Moreover, energy intake on MIR was only slightly higher than
complete bed rest with no activity [24.2 ± 0.8 kcal · kg1 · day1
(10)] and substantially less than either bed rest with activity [this bed-rest study, 30.8 ± 1.3 kcal · kg1 · day1
(34)] or sitting in a metabolic chamber at rest [29.7 ± 2.3 kcal · kg1 · day1
(8)]. Therefore, it is highly improbable that the MIR crew persons were in energy balance.
The magnitude of the energy deficit was apparently sufficiently great
to impact the whole body protein synthesis rate adversely (33).
Increased production of antioxidants in the face of decreased intake,
decreased total body protein synthesis, decreased oxidative metabolism,
and decreased need for antioxidants is therefore highly improbable.
Moreover, this argument does not explain the differences between 8-OH
DG and 8-iso-PGF2. The third option, decreased endogenous free-radical production, is the expected result if there is
a downregulation of intermediary metabolism in response to the
decreased energy intake and no increase in free-radical generation from radiation.
Different aspects of oxidative stress are measured by 8-OH DG and
8-iso-PGF2, namely DNA damage and cell membrane damage, respectively. A decreased flux through the electron transport chain
will generate fewer free radicals in the mitochondria. Mitochondria are
exceptionally well endowed with membranes; most of the internal structure of mitochondria is membranous. Any diminution of oxidative phosphorylation is likely to decrease oxidative damage to the internal
mitochondrial membrane arrays.
Other arguments support the decrease in isoprostane production being
related to energy metabolism. First, on MIR, the percentage of decrease
in inflight energy intake from the preflight intake showed a
correlation with the percentage of decrease in isoprostane (unextracted) production inflight (r2 = 0.62, P = 0.065, and r2 = 0.65, P = 0.060 normalized to creatinine). Second, finding a decrease
inflight in isoprostane excretion was not unique to MIR. A decrease in
isoprostane excretion was also found with the LMS mission, where there
was also a significant reduction in dietary intake inflight (Table 3).
In contrast, with the bed-rest study, dietary intake was approximately
the same before and during bed rest, and isoprostane excretion was
unchanged (Table 4).
It is not known why dietary intake is decreased during spaceflight or
why there is an apparent inverse relationship between exercise and
intake (30, 34). We suggest that the adverse effects of exercise on
energy intake during spaceflight are a consequence of decreased
efficiency in disposing of the heat produced during exercise.
Thermoregulatory mechanisms are less efficient in microgravity (and in
bed rest) for a number of reasons (5, 6, 9). First, blood flow to the
extremities is decreased, and this reduces the effective surface area
available for convection cooling (5, 9, 26). Second, plasma volume is
reduced during spaceflight (16), and this reduces the ability to
transfer heat from the core to the periphery. To compensate, either the
rate of blood flow perfusing the peripheral capillaries has to be
increased, or it will take longer to dissipate the heat. The latter is
more likely; cardiac output is less during exercise in microgravity than it is on the ground (5). Third, unlike on the ground, where sweat
water forms into beads, which have a large surface area, in
microgravity sweat water forms a coherent sheet on the body, sweat
losses after exercise are decreased in microgravity (17). Convertino
(5) suggested that the high level of skin wetness suppresses sweating.
Also, water is an excellent insulator, and this contributes to the
decreased ability to dispose of excess heat. The cumulative result of
these effects is that dissipating the excess heat generated during
exercise takes longer than it does on the ground.
As long as heat disposal is in progress, blood will be diverted away
from the gut to the periphery (2, 13). Diversion of blood away from the
gut will lead to a suppression of intake, because signals to the
appetite center from the gut (neural and endocrine) to the brain will
act to reduce food intake because the gut is not ready to process food
(2). The greater the amount of aerobic exercise, the more time is
needed for heat dissipation and the longer blood flow is diverted away
from the gut, resulting in the inverse relationship between exercise
and energy intake. This hypothesis also explains the unexpected
observation that astronauts on a given mission appear to synchronize
their intake (Fig. 3 in Ref. 34). The amount and type of exercise done
on these various missions (Skylab, Space Life Sciences missions 1 and
2, and the LMS mission) were part of the mission requirements and thus
were the same for all the crew for a given mission, but differed
between the missions. Improving heat dissipation after exercise by
increasing airflow may attenuate the appetite loss.
Postflight.
Oxidative damage was increased after spaceflight on MIR. Both 8-OH DG
and 8-iso-PGF
were increased by more than twofold after 3+ mo on MIR
(Table 1, Fig. 1). 8-iso-PGF2 was also increased by a
lesser amount after bed rest (Table 4), but not after 17 days on the
space shuttle (Table 3).
Radiation. This study found no evidence for increased free-radical production from high-energy radiation. The radiation flux ranged between 30 and 100 mREM/day with a mean of 60 mREM/day. During these flights there were no bursts of high-energy radiation (personal communication, Dr. V. S. Schneider). Free-radical production from ionizing radiation is qualitatively and quantitatively different from that of metabolic origin. A "hit" from a high-energy particle is an infrequent event compared with the continuous flux of low-energy semistable free radicals generated from metabolic processes. But the collateral damage from the impact of a single high-energy incoming particle can be extensive because of the very high energies involved. The weak trend toward an increase in 8-OH DG production inflight can be accounted for by the decreased synthesis of host defense proteins secondary to the overall depression of protein synthesis.
Different results may be found with other missions in different orbits exposed to different degrees of solar and extragalactic radiation and where nutritional status is not a confounding variable. In the present study, any radiation-induced damage could have been obscured by the metabolic decrease in free-radical production. Any apparent benefit from the "protective effects" of undernutrition against oxidative damage is counterbalanced by the much more serious consequences of undernutrition. In summary, 1) oxidative damage was decreased during long-duration spaceflight on MIR secondary to an overall decrease in metabolic activity; 2) inflight, undernutrition may have a protective effect against oxidative damage; and 3) oxidative damage was increased after return from several months in earth orbit.| |
ACKNOWLEDGEMENTS |
|---|
Special thanks are due to the astronauts and cosmonauts who participated in this experiment. We would like to thank Robert Pietrzyk, M.S. (Wyle Laboratories), for acting as experiment manager, Barbara Rice, R.D. (Wyle Laboratories), for the dietary data, and Scott M. Smith, Ph.D. (NASA-JSC) for coordinating the project, as well as numerous unnamed people at NASA and the RSA who did much of the work in collecting the data in Russia and in the US. M. R. Donaldson provided technical assistance with some of the analyses. Finally, we wish to acknowledge a helpful discussion with Dr. Karl Kirsch, Free University of Berlin, on thermoregulation during spaceflight.
| |
FOOTNOTES |
|---|
This study was supported by National Aeronautics and Space Administration contract no. NAS9-19409, National Institutes of Health Grant #RO1-14098, and internal UMDNJ funds.
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Address for reprint requests and other correspondence: T. P. Stein, Dept. of Surgery, Univ. of Medicine and Dentistry of New Jersey, School of Osteopathic Medicine, 2 Medical Center Drive, Stratford, NJ 08084 (E-mail: tpstein{at}umdnj.edu).
Received 14 April 1999; accepted in final form 12 October 1999.
| |
REFERENCES |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
1.
Ames, B. N.
Endogenous oxidative DNA damage, aging, and cancer.
Free Radical Res. Comm.
7:
121-128,
1989.
2.
Brouns, F.,
and
E. Beckers.
Is the gut an athletic organ? Digestion, absorption and exercise.
Sports Med.
15:
242-257,
1993[ISI][Medline].
3.
Buravkova, L.,
and
E. Mailyan.
Oxidative phosphorylation in rat skeletal muscles after space flight on board biosatellites.
J. Gravit. Physiol.
4:
127-128,
1997.
4.
Burrough, B.
Dragonfly: NASA and the Crisis Aboard MIR. New York: HarperCollins, 1998, p. 108-113, 334.
5.
Convertino, V. A.
Exercise as a countermeasure for physiological adaptation to prolonged spaceflight.
Med. Sci. Sports Exerc.
28:
999-1014,
1996[ISI][Medline].
6.
Fortney, S. M.,
V. Mikhaylov,
S. M. Lee,
Y. Kobzev,
R. R. Gonzalez,
and
J. E. Greenleaf.
Body temperature and thermoregulation during submaximal exercise after 115-day spaceflight.
Aviat. Space Environ. Med.
69:
137-141,
1998[Medline].
7.
Fraga, C. G.,
M. K. Shigenaga,
J. W. Park,
P. Degan,
and
B. N. Ames.
Oxidative damage to DNA during aging: 8-hydroxy-2'-deoxyguanosine in rat organ DNA and urine.
Proc. Natl. Acad. Sci. USA
87:
4533-4537,
1990
8.
Goran, M. I.,
E. T. Poehlman,
and
E. Danforth, Jr.
Experimental reliability of the doubly labeled water technique.
Am. J. Physiol. Endocrinol. Metab.
266:
E510-E515,
1994
9.
Greenleaf, J. E.,
and
R. D. Reese.
Exercise thermoregulation after 14 days of bed rest.
J. Appl. Physiol.
48:
72-78,
1980
10.
Gretebeck, R. J.,
D. A. Schoeller,
E. K. Gibson,
and
H. W. Lane.
Energy expenditure during antiorthostatic bed rest (simulated microgravity).
J. Appl. Physiol.
78:
2207-2211,
1995
11.
Gutteridge, J. M. C.,
and
B. Halliwell.
Antioxidants in nutrition, health and disease.
In: Antioxidants in Nutrition, Health and Disease. Oxford, UK: Oxford University Press, 1994.
12.
Halliwell, B.
Antioxidants and human disease: a general introduction.
Nutr. Rev.
55:
S44-S52,
1997[ISI][Medline].
13.
Ho, C. W.,
J. L. Beard,
P. A. Farrell,
C. T. Minson,
and
W. L. Kenney.
Age, fitness, and regional blood flow during exercise in the heat.
J. Appl. Physiol.
82:
1126-1135,
1997
14.
Hollander, J.,
M. Gore,
R. Fiebig,
R. Mazzeo,
S. Ohishi,
H. Ohno,
and
L. L. Ji.
Spaceflight downregulates antioxidant defense systems in rat liver.
Free Radical Biol. Med.
24:
385-390,
1998[ISI][Medline].
15.
Lane, H. W.,
R. J. Gretebeck,
D. A. Schoeller,
J. Davis-Street,
R. A. Socki,
and
E. K. Gibson.
Comparison of ground-based and space flight energy expenditure and water turnover in middle-aged healthy male US astronauts.
Am. J. Clin. Nutr.
65:
4-12,
1997
16.
Leach, C. S.,
C. P. Alfrey,
W. N. Suki,
J. I. Leonard,
P. C. Rambaut,
L. D. Inners,
S. M. Smith,
H. W. Lane,
and
J. M. Krauhs.
Regulation of body fluid compartments during short-term spaceflight.
J. Appl. Physiol.
81:
105-116,
1996
17.
Leach, C. S.,
J. I. Leonard,
P. C. Rambaut,
and
P. C. Johnson.
Evaporative water loss in man in a gravity-free environment.
J. Appl. Physiol.
45:
430-436,
1978
18.
Lee, M. D.,
R. Tuttle,
and
B. Girten.
Effect of spaceflight on oxidative and antioxidant enzyme activity in rat diaphragm and intercostal muscles.
J. Gravit. Physiol.
2:
68-69,
1995.
19.
Loft, S.,
P. N. Larsen,
A. Rasmussen,
A. Fischer-Nielsen,
S. Bondesen,
P. Kirkegaard,
L. S. Rasmussen,
E. Ejlersen,
K. Tornoe,
R. Bergholdt,
Oxidative DNA damage after transplantation of the liver and small intestine in pigs.
Transplantation
59:
16-20,
1995[ISI][Medline].
20.
Loft, S.,
and
H. E. Poulsen.
Estimation of oxidative DNA damage in man from urinary excretion of repair products.
Acta Biochim. Pol.
45:
133-144,
1998[ISI][Medline].
21.
Lunec, J.
Free radicals: their involvement in disease processes.
Ann. Clin. Biochem.
27:
173-182,
1990.
22.
Markin, A. A.,
I. A. Popova,
E. G. Vetrova,
O. A. Zhuravleva,
and
O. I. Balashov.
Lipid peroxidation and activity of diagnostically significant enzymes in cosmonauts after flights of various durations.
Aviakosm. Ekolog. Med.
31:
14-18,
1997[Medline].
23.
Markin, A. A.,
and
O. A. Zhuravleva.
Lipid peroxidation and antioxidant defense system in rats after a 14-day space flight in the "Space-2044" spacecraft.
Aviakosm. Ekolog. Med.
27:
47-50,
1993[Medline].
24.
Morrow, J. D.,
B. Frei,
A. W. Longmire,
J. M. Gaziano,
S. M. Lynch,
Y. Shyr,
W. E. Strauss,
J. A. Oates,
and
L. J. Roberts, II.
Increase in circulating products of lipid peroxidation (F2- isoprostanes) in smokers. Smoking as a cause of oxidative damage.
N. Engl. J. Med.
332:
1198-1203,
1995
25.
National Research Council-Committee on Space Biology and
Medicine-Space Studies Board A Strategy for Research in
Space Biology and Medicine Into the Next Century. chapt. 11, 1998, p. 171-193. Washington, DC: National Academy Press.
26.
Novak, L.
Our experience and evaluation of thermal control during space flight and simulated space environment.
Acta Astronautica
23:
179-186,
1991[ISI][Medline].
27.
Pryor, W. A.,
and
K. Stone.
Oxidants in cigarette smoke. Radicals, hydrogen peroxide, peroxynitrate, and peroxynitrite.
Ann. NY Acad. Sci.
686:
12-28,
1993[ISI][Medline].
28.
Rambaut, P. C.,
C. S. Leach,
and
J. I. Leonard.
Observations in energy balance in man during spaceflight.
Am. J. Physiol. Regulatory Integrative Comp. Physiol.
233:
R208-R212,
1977.
29.
Rokach, J.,
S. P. Khanapure,
S. W. Hwang,
M. Adiyaman,
J. A. Lawson,
and
G. A. FitzGerald.
The isoprostanes: a perspective.
Prostaglandins
54:
823-851,
1997[ISI][Medline].
30.
Stein, T. P.,
M. J. Leskiw,
and
M. D. Schluter.
Diet and nitrogen metabolism during spaceflight on the shuttle.
J. Appl. Physiol.
81:
82-97,
1996
31.
Stein, T. P.,
and
M. D. Schluter.
Human skeletal muscle protein breakdown during spaceflight.
Am. J. Physiol. Endocrinol. Metab.
272:
E688-E695,
1997
32.
Stein, T. P.,
and
M. D. Schluter.
Plasma amino acids during human space flight.
Aviat. Space Environ. Med.
70:
250-255,
1998.
33.
Stein, T. P.,
M. J. Leskiw,
M. D. Schluter,
M. R. Donaldson,
and
I. Larina.
Protein kinetics during and after long-term spaceflight on MIR.
Am. J. Physiol. Endocrinol. Metab.
276:
E1014-E1021,
1999
34.
Stein, T. P.,
M. J. Leskiw,
M. D. Schluter,
R. W. Hoyt,
H. W. Lane,
R. E. Gretebeck,
and
A. D. LeBlanc.
Energy expenditure and balance during space flight on the shuttle: the LMS mission.
Am. J. Physiol. Regulatory Integrative Comp. Physiol.
276:
R1739-R1748,
1999
35.
Tucker, K. R.,
M. J. Seider,
and
F. W. Booth.
Protein synthesis rates in atrophied gastrocnemius muscles after limb immobilization.
J. Appl. Physiol.
51:
73-77,
1981
36.
Ushakov, A. S.,
and
T. F. Vlasova.
Free amino acids in human blood plasma during space flights.
Aviat. Space Environ. Med.
47:
1061-1064,
1976[Medline].
37.
Vorobyov, E. I.,
O. G. Gazenko,
A. M. Genin,
and
A. D. Egorov.
Medical results of Salyut-6 manned space flights.
Aviat. Space Environ. Med.
54:
S31-S40,
1983[Medline].
38.
West, J. B.,
A. R. Elliott,
H. J. Guy,
and
G. K. Prisk.
Pulmonary function in space.
J. Am. Med. Assoc.
277:
1957-1961,
1997[Abstract].
This article has been cited by other articles:
|
|
 |
|
  T. P. Stein and C. E. Wade Metabolic Consequences of Muscle Disuse Atrophy J. Nutr., July 1, 2005; 135(7): 1824S - 1828S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. J. Janssen Isoprostanes: an overview and putative roles in pulmonary pathophysiology Am J Physiol Lung Cell Mol Physiol, June 1, 2001; 280(6): L1067 - L1082. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
