Reversal of weightlessness-induced musculoskeletal losses with androgens: quantification by MRI.

Microgravity causes rapid decrement in musculoskeletal mass is associated with a marked decrease in circulatory testosterone levels, as we reported in hindlimb-suspended (HLS) rats. In this model which simulates microgravity, we hypothesized that testosterone supplementation should prevent these losses, and we tested this in two studies. Muscle volumes and bone masses were quantitated by using magnetic resonance imaging (MRI) on day 12. In the first study, 12-wk-old Sprague-Dawley rats that were HLS for 12 days lost 28.5% of muscle volume (53.3 +/- 4.8 vs. 74.5 +/- 3.6 cm3 in the ground control rats; P < 0.001) and had a 5% decrease in bone mineral density (BMD) (P < 0.05). In the second study, 30 male 12-wk-old Wistar rats were HLS and were administered either a vehicle (control), testosterone, or nandrolone decanoate (ND). An additional 20 rats were used as ground controls, one-half of which received testosterone. HLS rats had a significant reduction in muscle volume (42.9 +/- 3.0 vs. 56 +/- 1.8 cm3 in ground control rats; P < 0.01). Both testosterone and ND treatments prevented this muscle loss (51.5 +/- 2 and 51.6 +/- 1.2 cm3, respectively; a 63% improvement; P < 0. 05). There were no statistical differences between the two active treatment groups nor with the ground controls. Similarly, there was an 85% improvement in BMD in the testosterone group (1.15 +/- 0.04 vs. 1.04 +/- 0.04 density units in vehicle controls; P < 0.05) and a 76% improvement in the ND group (1.13 +/- 0.07 density units), whereas ground control rats had a BMD of 1.17 +/- 0.03 density units. Because serum testosterone levels are markedly reduced in this model of simulated microgravity, androgen replacement seems to be a rational countermeasure to prevent microgravity-induced musculoskeletal losses.     

AQP9: a novel target for bone loss induced by microgravity

The aim of current study was to elucidate whether aquaporin-9 (AQP9) expression was involved in the progression of bone loss induced by microgravity. We used the hind-limb suspension (HLS) mice model to simulate microgravity and induce bone loss. It was found that HLS exposure decreased femur bone mineral density (BMD), and enhanced femur AQP9 mRNA and protein levels. Then, the relationship between AQP9 mRNA expression and BMD was studied and it was showed that femur AQP9 mRNA level was negatively related to femur BMD in mice exposed to HLS. We sought to exam the function of AQP9 in the femur using the AQP9-null mice. It was found that AQP9 knockout attenuated bone loss and inhibited osteoclastogenesis under the condition of HLS exposure, but had no similar effect on bone under normal physiological conditions. In addition, it was found that exposure to simulated hypergravity or exercise training, main countermeasures against microgravity, reduced AQP9 mRNA and protein levels in femur of mice. Moreover, it was found that both aging and estrogen deprivation, another two risk factors of bone loss, had no significant effect on femur AQP9 expression. In conclusion, AQP9 plays an important role in the development of microgravity-induced bone loss, and may be a potential target for the prevention or management of microgravity-induced bone loss.     

模拟失重不同时长对大鼠抑郁样行为的影响

目的 本研究旨在观察不同持续时间的模拟失重对大鼠抑郁样行为和海马超氧化物歧化酶（SOD）和过氧化氢酶（CAT）的影响，以探究其影响及可能的作用机制。方法 采用后肢悬挂（HLS）尾吊法模拟大鼠失重状态。将大鼠分为对照组和不同模拟失重时间尾吊组（尾吊时长分别为1、2、3、4周）。采用旷场实验（OFT）、新物体识别实验（NORT）、强迫游泳实验（FST）观察大鼠抑郁样行为，采用酶联免疫吸附试验（ELISA）法测定海马SOD和CAT活性。结果 OFT结果显示，与对照组相比，HLS不同时间大鼠的僵滞时间增加（P<0.05，P<0.01）。在NORT中，与对照组相比，HLS不同时间大鼠对新物体的探索潜伏期增加，探索次数和时间减少（P<0.05，P<0.01）。在FST中，与对照组相比，HLS不同时间大鼠在FST中的不动时间增加，攀爬次数减少（P<0.05，P<0.01）。与对照组相比，HLS不同时间组大鼠海马组织中SOD和CAT水平均下降（P<0.05，P<0.01）。结论 短时间或长时间的失重都会导致大鼠产生类抑郁样行为。     

Short-term simulated weightlessness enhances response of L-type calcium channel to angiotensin II in cerebral vascular smooth muscle cells in rats

Some studies suggest that the calcium channels and rennin-angiotensin system (RAS) play pivotal roles in the region-specific vascular adaptation due to simulated weightlessness. This study was designed to clarify if angiotensin II (Ang II) was involved in the adaptational change of the L-type calcium channel (Ca(L)) in the cerebral arterial vascular smooth muscle cells (VSMCs) under simulated weightlessness. Tail suspension (SUS) for 3 d was used to simulate immediate early cardiovascular changes to weightlessness. Then VSMCs in cerebral basilar artery were enzymatically isolated using papain, and Ca(L) current (barium instead of calcium as current carrier) in VSMCs was measured by whole-cell patch-clamp techniques. The results showed that 3-day simulated weightlessness significantly increased current density of Ca(L). However, I-V relationships of normalized peak current densities and steady-state activation curves of Ca(L) were not affected by simulated weightlessness. Although Ang II significantly increased current densities of Ca(L) in both SUS and control rats, the increase of Ca(L) current density in SUS rats was much more than that in control rats. These results suggest that 3-day simulated weightlessness induces the adaptational change of Ca(L) in cerebral VSMCs including increased response to Ang II, indicating that Ang II may play an important role in the adaptational change of cerebral arteries under microgravity.     

Long-term (6-wk) hindlimb suspension inhibits spermatogenesis in adult male rats.

The International Space Station will allow extended habitation in space and long-term exposure to microgravity (microG). A concern is the impact of long-term microG exposure on the ability of species to reproduce. The model often used to simulate microG is rat hindlimb suspension (HLS), where the hindlimbs are elevated above the cage floor with a tail harness. Experiments described here are the first to examine the effect of long-term HLS on testicular function in adult male rats. Free-roaming (controls), animals with only the tail harnessed but hindlimbs in contact with the cage floor (TO), and HLS animals were tested for 6 wk. Cryptorchidism was prevented in TO and HLS animals by partial constriction of the inguinal canal with sutures. All parameters were compared at the end of the 6-wk experiment. Testicular weights and spermatogenesis were significantly reduced by HLS, such that no spermatogenic cells beyond round spermatids were present and epididymides were devoid of mature sperm. In many tubules, loss of all germ cells, except a few spermatogonia, resulting in histopathology similar to the Sertoli cell, was observed. Spermatogenesis appeared unaffected in control and TO animals. Sertoli and Leydig cell appearance, testosterone, luteinizing hormone, and follicle-stimulating hormone levels, and epididymal and seminal vesicle weight were unchanged by HLS. Cortisone was not elevated by HLS; thus stress may not be a factor. These results demonstrate that spermatogenesis is severely inhibited by long-term HLS, whereas testicular androgen production is not. These results have significant implications regarding serious effects of long-term exposure to microG on the reproductive capability of scrotal mammals, including humans.     

Microgravity effect on testicular functions

In mammals spaceflight influences spermatogenesis since spermatogonial germ cell proliferation, compared to synchronous controls, is lightly decreased in irradiated or flown rats. Moreover, changes of the plasmatic testosterone production was described either in flight rats, or in rats maintained in simulated microgravity conditions. The hormonal levels of the astronauts change as it has been previously described, including hormones involved in the regulation of spermatogenesis such as testosterone and luteinizing hormone (LH). In microgravity conditions, human testosterone levels decreased whereas circulating LH levels increased. To study the effect of simulated microgravity on mammalian spermatogenesis we have utilized the Rotary Cell Culture System (RCCS) and we have cultured testicular fragments isolated from prepuberal rats in a chemically defined medium for three days under microgravity conditions. As control we have cultured the same amount of fragments at unit gravity. The morphology of the samples has been studied and the number of proliferating cells has been counted in control samples and in samples maintained in RCCS. The results indicate that the number of duplicating cells in the tubules was significantly increased in the microgravity-cultured fragments. The amount of testosterone secreted in the culture medium has been also evaluated and in RCCS samples the amount of the hormone was higher respect to the control samples.     

回转对离体大鼠成骨细胞中骨粘连蛋白及骨桥素mRNA的影响

为研究模拟失重对成骨细胞细胞外基质mRNA的影响,实验采用离体人鼠成骨细胞水平轴回转模拟失重效应,用RT-PCR技术分别检测成骨细胞中骨桥素(osteopontin,OPN)及骨粘连蛋白(osteonectin,ON)mRNA的水平,并观察细胞培养液中碱性磷酸酶(alkaline phosphatase,ALP)的活性和骨钙素(osteocalcim, BGP)含量的变化。结果观察到,分别回转24、48、72h后,OPN、ON的mRNA含量及细胞培养液中BGP含量均显著下降,细胞培养液中ALP活性也呈下降趋势。上述结果表明,模拟失重后成骨细胞OPN及ON的表达下调,进而使BGP及ALP的分泌量减少,从而导致骨钙化能力降低,提示模拟失重导致的细胞外基质蛋白基因表达下降可能是模拟火重引起骨丢失的原因之一。     

A Hypomagnetic Field Aggravates Bone Loss Induced by Hindlimb Unloading in Rat Femurs

A hypomagnetic field is an extremely weak magnetic field—it is considerably weaker than the geomagnetic field. In deep-space exploration missions, such as those involving extended stays on the moon and interplanetary travel, astronauts will experience abnormal space environments involving hypomagnetic fields and microgravity. It is known that microgravity in space causes bone loss, which results in decreased bone mineral density. However, it is unclear whether hypomagnetic fields affect the skeletal system. In the present study, we aimed to investigate the complex effects of a hypomagnetic field and microgravity on bone loss. To study the effects of hypomagnetic fields on the femoral characteristics of rats in simulated weightlessness, we established a rat model of hindlimb unloading that was exposed to a hypomagnetic field. We used a geomagnetic field-shielding chamber to generate a hypomagnetic field of <300 nT. The results show that hypomagnetic fields can exacerbate bone mineral density loss and alter femoral biomechanical characteristics in hindlimb-unloaded rats. The underlying mechanism might involve changes in biological rhythms and the concentrations of trace elements due to the hypomagnetic field, which would result in the generation of oxidative stress responses in the rat. Excessive levels of reactive oxygen species would stimulate osteoblasts to secrete receptor activator of nuclear factor-κB ligand and promote the maturation and activation of osteoclasts and thus eventually cause bone resorption.     

Daily 4-h head-up tilt is effective in preventing muscle but not bone atrophy due to simulated microgravity

To assess the potential value of intermittent artificial gravity as an efficient countermeasure, our previous studies have showed that daily 4-h standing (STD) is sufficient in counteracting muscle atrophy but not bone atrophy induced by simulated microgravity. The aim of the present study was to determine whether intermittent gravitational loading by daily 2-h or 4-h, +45 degrees head-up tilt (HUT) is more effective than STD in counteracting muscle and, particularly, bone atrophy due to simulated microgravity. Sprague-Dawley male rats weighing 290-300 g were subjected to a 28-d tail-suspension to simulate microgravity deconditioning. Daily HUT for 2, or 4 h was used to provide intermittent gravitational loading in foot-ward and tail-ward directions. The results showed that 4 h/d HUT was sufficient, and 2 h/d was less effective, in preventing adverse changes in muscle weights, fiber types, and cross-sectional areas (CSA) of muscles due to a 28-d simulated microgravity. The % protections by 4 h/d HUT in maintaining the CSAs of type I fibers in soleus, medial and lateral gastrocnemius and extensor digitorum longus muscles were 103%, 82%, 102%, and 83%, respectively. However, according to changes in physical and mechanical properties of femur, daily 4-h HUT was ineffective in attenuating the adverse changes in bone due to a 28-d simulated microgravity. Reductions in wet, dry, and ash weights and decreases in mechanical strength of femur did not show significant improvement by daily 2-h or 4-h HUT. Taken together, the findings indicate that the countermeasure effectiveness of daily 2-h or 4-h HUT for muscles is comparable with that by daily STD with the same durations. Daily 4-h HUT, as 4-h STD, is also ineffective in attenuating adverse changes in bone mass, but seems partially effective in preventing declines in mechanical properties due to simulated microgravity.     

Contractile and connective tissue protein content of human skeletal muscle: effects of 35 and 90 days of simulated microgravity and exercise countermeasures

We examined the effects of 35 and 90 days of simulated microgravity with or without resistance-exercise (RE) countermeasures on the content of the general skeletal muscle protein fractions (mixed, sarcoplasmic, and myofibrillar) and specific proteins that are critical for muscle function (myosin, actin, and collagen). Subjects from two studies, using either unilateral lower limb suspension (ULLS) or bed rest (BR), comprised four separate groups: 35 days ULLS (n =11), 35 days ULLS+RE (n = 10), 90 days BR (n = 9), and 90 days BR+RE (n = 8). RE consisted of four sets of seven maximal concentric and eccentric repetitions of the quadriceps femoris muscles that were performed 2 or 3 times per week. Pre- and post-simulated weightlessness muscle biopsies were analyzed from the vastus lateralis of all groups and the soleus of the 35-day ULLS and 90-day BR groups. The general protein fractions and the specific proteins myosin, actin, and collagen of the vastus lateralis were unchanged (P > 0.05) in both control and countermeasures groups over 35 and 90 days, despite large changes in quadriceps femoris muscle volume (35 days ULLS: -9%, 35 days ULLS+RE: +8%; and 90 days BR: -18%, 90 days BR+RE: -1%). The soleus demonstrated a decrease in mixed (35 days ULLS: -12%, P = 0.0001; 90 days BR: -12%, P = 0.004) and myofibrillar (35 days ULLS: -12%, P = 0.009; 90 days BR: -8%, P = 0.04) protein, along with large changes in triceps surae muscle volume (35 days ULLS: -11%; 90 days BR: -29%). Despite the loss of quadriceps femoris muscle volume or preservation with RE countermeasures during simulated microgravity, the quadriceps femoris muscles are able to maintain the concentrations of the general protein pools and the main contractile and connective tissue elements. Soleus muscle protein composition appears to be disproportionately altered during long-duration simulated weightlessness.     

The Impact of Exogenic Testosterone and Nortestosterone-Decanoate Toxicological Evaluation Using a Rat Model

The impact of exogenic testosterone (T): 1.5 and 3.0 mg/kg.bw) and 19-nortestosterone 17-decanoate (ND): 1.5 and 7.5 mg/kg.bw) in castrated male rats was evaluated based on: (a) weight increase of the androgen target tissues, respecting the Hershberger methodology; (b) the 17α and β-testosterone, 17 α and β-estradiol and 17 α and β-nortestosterone levels using the GC-MS/MS technique; and (c) observation of the serum free thyroxine levels (T₄). Results revealed that T and ND significantly increased the weight of androgen target tissues as follows: ND was more influential on seminal vesicles, levator ani-bulbocavernosus muscle (LABC) and Cowper''s glands and T (at a dose of 3.0 mg/kg.bw) influenced the weight of the ventral prostate and glans penis. Serum samples analyzed for steroid hormone levels showed the presence of 17β-testosterone, 17β-estradiol and 17β-nor-testosterone, in castrated male rats injected with testosterone and nortestosterone, but no significant differences were found between thyroid responses and thyroid hormone levels. The results of this research proved the disrupting activity of T and ND when administered in high doses and the useful application of the Hershberger bioassay in the case of ND.     

17β-Hydroxyestra-4,9,11-trien-3-one (trenbolone) exhibits tissue selective anabolic activity: effects on muscle, bone, adiposity, hemoglobin, and prostate

Selective androgen receptor modulators (SARMs) now under development can protect against muscle and bone loss without causing prostate growth or polycythemia. 17β-Hydroxyestra-4,9,11-trien-3-one (trenbolone), a potent testosterone analog, may have SARM-like actions because, unlike testosterone, trenbolone does not undergo tissue-specific 5α-reduction to form more potent androgens. We tested the hypothesis that trenbolone-enanthate (TREN) might prevent orchiectomy-induced losses in muscle and bone and visceral fat accumulation without increasing prostate mass or resulting in adverse hemoglobin elevations. Male F344 rats aged 3 mo underwent orchiectomy or remained intact and were administered graded doses of TREN, supraphysiological testosterone-enanthate, or vehicle for 29 days. In both intact and orchiectomized animals, all TREN doses and supraphysiological testosterone-enanthate augmented androgen-sensitive levator ani/bulbocavernosus muscle mass by 35-40% above shams (P ≤ 0.001) and produced a dose-dependent partial protection against orchiectomy-induced total and trabecular bone mineral density losses (P < 0.05) and visceral fat accumulation (P < 0.05). The lowest doses of TREN successfully maintained prostate mass and hemoglobin concentrations at sham levels in both intact and orchiectomized animals, whereas supraphysiological testosterone-enanthate and high-dose TREN elevated prostate mass by 84 and 68%, respectively (P < 0.01). In summary, low-dose administration of the non-5α-reducible androgen TREN maintains prostate mass and hemoglobin concentrations near the level of shams while producing potent myotrophic actions in skeletal muscle and partial protection against orchiectomy-induced bone loss and visceral fat accumulation. Our findings indicate that TREN has advantages over supraphysiological testosterone and supports the need for future preclinical studies examining the viability of TREN as an option for androgen replacement therapy.     

Changes in myocardial contractility and contractile proteins after four weeks of simulated [correction of simulate] weightlessness in rats

The interaction between the gravitational field, the position of the body, and the functional characteristics of the blood vessels determines the distribution of intravascular volume. In turn, this distribution determines cardiac pump function. One of the most profound circulatory changes that occurs in man during exposure to weightlessness is a cephalad redistribution of fluid caused by the lack of hydrostatic pressure in this microgravitative environment. The cephalad redistribution of fluid results in a loss of blood volume and then induces a decrease in preload. Recently, a decrease in sensitivity of arteriole to catecholamine has reported in rats of simulated weightlessness. This change in arteriole may reduce afterload. As a result, cardiovascular system may be shifted to a hypokinetic state during weightlessness condition for long-term. Echocardiographic data from astronauts during space flight showed an increase in heart rate, a 12 % decrease in stroke volume, and a 16 % decrease in left end diastolic volume. Electron-microscopic studies have shown changes in cardiac morphology in rats after exposure to microgravity for 7-12.5 days. After the COSMOS 2044 flight for 14 days, the light-microscopic studies have shown an atrophy of papillary muscles in rats left cardiac ventricle. It is not clear whether the function of atrophic myocardium is impaired. The data in three aspects as mentioned above suggest that weightlessness or simulated weightlessness may decrease the myocardial function. However, definite changes in cardiac performance have been hard to prove due to many limits. This studies were to answer two questions: Is the myocardial contractility depressed in rats subjected to simulated weightlessness for four weeks? What are the underlying mechanisms of the changing contractility?     

Some vegetables (commonly consumed by humans) efficiently modulate bone metabolism

We have hypothesized that some vegetables which are part of the regular human diet may contain modulators of bone metabolism. To mimic a typical Western diet with large proportions of refined components, rats were pair-fed a semi-purified diet to which, in the treated animals, the dried material under investigation was added. Effects are expressed as % of untreated control. Bone parameters in rats were assessed in the proximal tibia by pQCT. Bone resorption (BR) was assessed by the urinary excretion of [3H]-tetracycline from prelabeled rats. Daily administration of 1 g of onion during 4 weeks increased total bone mineral content by 17.4% (p<0.05), trabecular bone mineral density by 13.6% (p<0.05). One g of onion/day administered to male rats blunted BR by 23-/+5% (p<0.05). Daily administration of onion to ovariectomized rats inhibited BR in a dose-dependent manner. At the highest dose (1.5 g of onion) BR was inhibited by 26-/+4% (p<0.01) as compared to 24-/+3% (p<0.001) for estradiol (27microg/kg/day). An additional 13 vegetables displayed significant effects on BR at the dose of 1g/day. Interestingly, 1g/day of soy did not inhibit BR in this model. Also, skimmed milk, meat and egg (all 1 g/day) were ineffective. Thus, common vegetables consumed by humans potently modulate bone metabolism in the rat. This opens the possibility to develop the basis for a low-cost, safe and effective nutritional approach to osteoporosis.     

Changes in bone volume and bone resorption by olpadronate treatment in an experimental model of uremic bone disease

Thirty male adult Wistar rats (300-/+10 g body weight) underwent either 5/6 nephrectomy (Nx, n=20) or sham operation (SHAM, n=10) to determine olpadronate effects in an experimental model of uremic bone disease. For a 38-day period, 10 rats received olpadronate (16microg/100g bw) once a week (Nx+OPD) and the other vehicle (Nx). SHAM received vehicle. At baseline, treatment onset (t=7 days) and end of study (t=45 days) calcium, phosphorus, creatinine, bone alkaline phosphatase (b-ALP) and deoxypyridinoline crosslinks (DPyr) were determined. At t=0 and t=45 bone mineral density (BMD) was measured by DXA. At t=45 the right tibia was removed for bone histology. There were no differences in serum calcium. Phosphorus increased in Nx and Nx+OPD compared to SHAM (p相似文献   

Effects of spaceflight and cage design on abdominal muscles of male rodents

We examined the effects of a 16-day spaceflight mission on the size of muscle fibers in the rectus abdominis, external oblique and transversus abdominis muscles of adult male Fisher rats. The rats were individually housed in orbit, in contrast to the one previous spaceflight investigation of the same muscles, where the rats were group-housed pregnant females. The cross-sectional area of the muscle fibers was used as a measure of muscle atrophy or hypertrophy. The transversus, which is presumed to be the primary expiratory muscle and consequently works against internal hydrostatic pressures that are not likely to change much between 1 G and weightlessness, did not change in size. However, both the rectus abdominis (a spinal flexor) and the external oblique (a rotator of the torso), which resist gravity in the 1 G environment, showed significant signs of atrophy after extended exposure to microgravity. The atrophy of the external oblique was diametrically opposite to hypertrophy of the same muscle observed in group-housed rodents previously exposed to spaceflight. Although the two missions differed in several factors, such as the gender of the rats and mission duration, we believe that housing of the animals was the key factor that accounted for the different responses of the external oblique. Previous research has shown that group-housed rats in spaceflight exhibited seven times more rotations of their torsos than matched ground controls. Thus unloading of the musculoskeletal system may not be achieved in weightlessness when animals have the freedom to interact with each other.     

Evaluation of the preventive effect of isoflavone extract on bone loss in ovariectomized rats

To examine a potential role for soybean phytoestrogens in postmenopausal bone loss, twenty-four 12-week-old Sprague-Dawley rats were divided randomly into 4 groups and given controlled diets for 16 weeks. The treatment groups were as followed: sham operated, ovariectomized (OVX) control, OVX + isoflavone extract (6.25 g/kg), and OVX + 17beta-estradiol (4 mg/kg). OVX treatments reduced femoral and fourth lumbar vertebral bone density and mineral content (p<0.01), decreased uterine weight (p<0.01), accelerated body weight increases (p<0.05), and increased the activities (p<0.01) of both serum alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP). Supplementation with isoflavone prevented the losses of bone density and mineral content caused by OVX (p<0.01). Although both isoflavone and 17beta-estradiol exhibited similar bone-sparing ability on the OVX-induced bone loss, the effect of isoflavone was not the same as that of 17beta-estradiol on the serum ALP and TRAP, body weight increase, and uterine weight change. We concluded that dietary supplementation with soybean isoflavone can prevent postmenopausal bone loss via a different mechanism of estrogen in OVX rats.     

Applied horizontal force increases impact loading in reduced-gravity running

The chronic exposure of astronauts to microgravity results in structural degradation of their lower limb bones. Currently, no effective exercise countermeasure exists. On Earth, the impact loading that occurs with regular locomotion is associated with the maintenance of bone's structural integrity, but impact loads are rarely experienced in space. Accurately mimicking Earth-like impact loads in a reduced-gravity environment should help to reduce the degradation of bone caused by weightlessness. We previously showed that running with externally applied horizontal forces (AHF) in the anterior direction qualitatively simulates the high-impact loading associated with downhill running on Earth. We hypothesized that running with AHF at simulated reduced gravity would produce impact loads equal to or greater than values experienced during normal running at Earth gravity. With an AHF of 20% of gravity-specific body weight at all gravity levels, impact force peaks increased 74%, average impact loading rates increased 46%, and maximum impact loading rates increased 89% compared to running without any AHF. In contrast, AHF did not substantially affect active force peaks. Duty factor and stride frequency decreased modestly with AHF at all gravity levels. We found that running with an AHF in simulated reduced gravity produced impact loads equal to or greater than those experienced at Earth gravity. An appropriate AHF could easily augment existing partial gravity treadmill running exercise countermeasures used during spaceflight and help prevent musculoskeletal degradation.     

Effect of spaceflight on oxidative and antioxidant enzyme activity in rat diaphragm and intercostal muscles

There are limited data regarding changes in oxidative and antioxidant enzymes induced by simulated or actual weightlessness, and any additional information would provide insight into potential mechanisms involving other changes observed in muscles from animals previously flown in space. Thus, the NASA Biospecimen Sharing Program was an opportunity to collect valuable information. Oxidative and antioxidant enzyme levels, as well as lipid perioxidation, were measured in respiratory muscles from rats flown on board Space Shuttle mission STS-54. The results indicated that there was an increasing trend in citrate synthase activity in the flight diaphragm when compared to ground based controls, and there were no significant changes observed in the intercostal muscles for any of the parameters. However, lipid peroxidation was significantly (p<0.05) decreased in the flight diaphragm. These results indicate that 6 day exposure to microgravity may have a different effect on oxidative and antioxidant activity in rat respiratory muscles when compared to data from previous 14 day hindlimb suspension studies.