Adrenal Ascorbic Acid Concentration Research Articles

Water‐immersion restraint stress disrupts nonenzymatic antioxidant defense systems through rapid and continuous ascorbic acid depletion in the adrenal gland of rats

We examined whether water-immersion restraint stress (WIRS) disrupts nonenzymatic antioxidant defense systems through ascorbic acid depletion in the adrenal gland of rats. Rats were exposed to WIRS for 0.5, 1.5, 3 or 6 h. WIRS increased serum adrenocorticotropic hormone, corticosterone and glucose concentrations and adrenal corticosterone content at each time point. WIRS increased adrenal lipid peroxide content at 3 and 6 h, and the increase was twofold higher than the unstressed level at 6 h. WIRS decreased adrenal ascorbic acid content at each time point, and the decrease reached one-third of the unstressed level at 6 h. WIRS increased adrenal reduced glutathione content at 0.5 and 6 h but reduced that content to half of the unstressed level at 6 h. WIRS increased adrenal α-tocopherol content at 1.5 h but returned that content to the unstressed level thereafter. When rats with 6 h of WIRS was orally preadministered with l-ascorbic acid (250 mg/kg), WIRS-induced changes in adrenal lipid peroxide, ascorbic acid and reduced glutathione contents were attenuated without any change in stress response. These results indicate that WIRS disrupts nonenzymatic antioxidant defense systems through rapid and continuous ascorbic acid depletion in the adrenal gland of rats.

Effect of long and short photoperiod on vasotocin neurons of paraventricular nuclei and adrenal function of water deprived Japanese quail

The responses of magnocellular neurons of paraventricular nuclei (PVN) and changes to adrenal activity to water deprivation in Japanese quail maintained under gonado-inhibitory and stimulatory photoperiods were examined. Water deprivation of 4 days resulted in a 12% decrease in body weight of sexually regressed short day (SD, 6L:18D) quail, while the decrease was more (18%) in sexually stimulated long day (LD, 16L:8D) quail. The increase in plasma osmolality following water deprivation was also more (47%) in LD than to SD quail (36%). Under the LD condition, quail had increased numbers, sizes and immunostaining of ir-AVT neurons of PVN compared to SD condition. A significant increase in the number of ir-AVT neurons was observed following 4 days of water deprivation in both SD and LD quail compared to their respective fully hydrated controls. However, the degree of response was more under the LD compared to the SD condition suggesting that gonado-stimulatory long days increase the activity/response of the AVT system. Increased adrenal ascorbic acid content (i.e., activity) was also observed to quail of LD when compared to SD treatment. However, osmotic stress led to adrenal hypertrophy and hyperactivity of quail of both of the photoperiodic regimes. Our findings indicate that not only osmotic stress but also photo-gonadal stimulation upregulates the expression of hypothalamic AVT genes and increases the localization of ir-AVT in many neurons of PVN. The above results support the existence of a parallel adrenal–gonad relationship and increase in adrenal function during osmotic stress, which also leads to simultaneous increase in AVT system. We conclude that photo-sexual conditions alter hypothalamic vasotocinergic and adrenal activity in Japanese quail and the degree of stimulation of the two systems following osmotic stress is higher under gonado-stimulatory LD conditions.

Varying responses to the rat forced-swim test under diurnal and nocturnal conditions

The paradox that experiments in behavioural pharmacology employing nocturnal rodent species are carried out almost exclusively in the resting phase of the animals' circadian cycle has remained largely unexamined and unquestioned. This is despite the fact that all major physiological systems in the body are intrinsically aligned with its natural circadian rhythm. The forced-swim test (FST) is a rodent model that is used extensively as a screening test for antidepressant activity. The objectives of the present study were to examine the behaviour of rats in the FST under diurnal and nocturnal conditions and, in addition, to profile the response of neurochemical, neuroendocrine, and cellular indices of stress at time points up to 120 min following exposure to the FST. The time spent in escape-oriented activity was significantly less when animals were tested in the dark phase. The profile of serum corticosterone and adrenal ascorbic acid concentrations indicates that the animals were less stressed by the test situation during the active (i.e., dark) phase of their circadian cycle. Similarly, increases in blood enzymatic markers of stress-induced cellular damage were less marked following FST exposure in the nocturnal period. Characteristic stress-induced increases in 5-HT turnover in the frontal cortex and amygdala observed in the diurnal phase were reversed in the nocturnal period. In conclusion, circadian differences in behaviour in the FST may be related to parallel alterations in the ability of animals to adapt to exposure to stress.

Olfactory Bulbectomy Provokes a Suppression of Interleukin-1β and Tumour Necrosis Factor-α Production in Response to an in vivo Challenge with Lipopolysaccharide: Effect of Chronic Desipramine Treatment

The olfactory bulbectomized (OB) rat has been developed as an animal model of depression and exhibits several behavioural and neurochemical characteristics that are qualitatively similar to those found in clinically depressed patients. In addition to the behavioural and neurochemical abnormalities seen in OB rats, it has been reported that these animals have alterations in a number ex vivo measures of immune function many of which are reversed following chronic antidepressant treatment. In the present study we sought to examine the effects of olfactory bulbectomy on responsiveness to an in vivo immune challenge with bacterial lipopolysaccharide (LPS; 100 μg/kg, i.p.). In addition, the effect of chronic treatment with the tricyclic antidepressant desipramine (7.5 mg/kg, i.p.) on bulbectomy related behavioural changes, hypothalamic-pituitary-adrenal axis activity and immune responsiveness was evaluated. To our knowledge this is the first time that in vivo immunological responsiveness has been examined in the OB rat model of depression. OB rats exhibited a characteristic hyperactive response in a novel ‘open field’ environment, which was attenuated following chronic desipramine treatment. LPS provoked a large increase in circulating interleukin (IL)-1β and tumour necrosis factor (TNF)-α in vehicle treated sham operated animals. Vehicle treated OB rats displayed a significant impairment in LPS-induced IL-1β (54%) and TNF-α (70%) secretion compared to their sham operated controls, an effect that was potentiated following chronic desipramine treatment. Furthermore, sham animals that were chronically treated with desipramine displayed decreases in LPS-provoked IL-1β (51%) and TNF-α (49%) secretion compared to vehicle treated counterparts. In addition, LPS-induced alterations in corticosterone and adrenal ascorbic acid concentrations were also attenuated by bulbectomy, an effect that was further enhanced following chronic desipramine treatment. In conclusion, these data provide evidence that olfactory bulbectomy in the rat impairs the ability of macrophages to produce the proinflammatory cytokines IL-1β and TNF-α following an in vivo challenge with bacterial LPS. Whilst chronic treatment with desipramine normalized the behavioural hyperactivity observed in OB rats, such treatment further impaired LPS-induced IL-1β and TNF-α secretion in bulbectomized rats.

Effects of adrenocorticotropic hormone and dexamethasone on adrenal and hepatic α-tocopherol concentrations

Studies were done to determine the effects of ACTH treatment on adrenal α-tocopherol (α-T) concentrations in female rats. Administration of dexamethasone (DEX) to inhibit endogenous ACTH secretion increased whole adrenal α-T levels as well as the fractional amount in adrenal cytosol. Adrenal ascorbic acid (AA) concentrations were unaffected by DEX. DEX treatment also had no effect on hepatic AA content but decreased α-T concentrations in the liver. The subcellular distribution of α-T in the liver was not altered by DEX. Administration of ACTH to DEX-treated animals decreased adrenal α-T content and restored the pattern of subcellular distribution to that seen in controls. ACTH had no effect on hepatic α-T concentrations or subcellular distribution. ACTH treatment also had no effect on AA concentrations in adrenals or livers. The results demonstrate that ACTH has a role in the regulation of adrenal α-T but the mechanism(s) involved remain to be determined. The data also indicate that glucocorticoids such as DEX directly influence hepatic α-T levels independent of their effects on ACTH secretion.

Forced Swim Test-Induced Endocrine and Immune Changes in the Rat: Effect of Subacute Desipramine Treatment

Previously it has been reported that forced swim test (FST) exposure activates the HPA–axis and produces alterations in both cellular and noncellular immunity in rats. Furthermore, there is evidence to suggest that pretreatment with antidepressants has a protective effect against FST-induced immune changes. The purpose of the present study was to examine the effect of subacute treatment with the tricyclic antidepressant desipramine (DMI, 5 and 10 mg/kg; IP) on immobility in the FST, and on FST-induced changes in endocrine and immune parameters in the rat. DMI treatment at a dose of 10 mg/kg produced a significant reduction in immobility time in the FST, while the 5 mg/kg dose was ineffective. FST exposure produced a significant increase in serum corticosterone and a decrease in adrenal ascorbic acid concentrations, neither of which were significantly attenuated by DMI pretreatment. There was a slight but nonsignificant suppression of PHA-induced lymphocyte proliferation 15 min post-FST exposure. However, DMI treatment produced a significant increase in lymphocyte proliferation at this time point. FST exposure caused a reduction in the percentage of lymphocytes and an increase in the percentage of neutrophils in the peripheral blood; DMI treatment failed to significantly alter these stress-induced changes. There was a profound reduction in relative spleen weight observed in DMI-treated animals 120 min post-FST exposure and this was accompanied by an increase in circulating RBC concentrations. In conclusion, although the FST-induced behavioral changes were normalized by DMI treatment the peripheral aberrations induced by FST exposure (with the exception of lymphocyte proliferation) were not. In addition, DMI pretreatment induced stress-like changes in corticosterone, adrenal ascorbic acid and leucocyte subpopulations in the control animals.

Meal-feeding and physical effort. 2. Metabolic changes induced by an acute exercise

In this study, rats under meal-feeding up to four weeks were submitted to a sudden exercise (swimming) to evaluate the effects of a behavior that requires mobilization of a large amount of energy on some physiological parameters already changed due to the chronic food-restriction. During exercise meal-fed rats: 1) increase the rate of gastric emptying; 2) maintain glycemia more steadily than the controls even during a long-lasting exercise; 3) maintain high liver glycogen concentration and its mobilization starts later on; 4) free fatty acid mobilization is lower than in the controls but during exercise do use much more; 5) keep more glycogen in the muscles (including the heart) than the controls but during the exercise do utilize much more; 6) are slightly less stressful (mainly after a longer exercise) than the controls as suggested by the adrenal ascorbic acid content.

Accelerated gluconeogenic processes in the ground squirrel ( Citellus citellus) during the arousal from hibernation

1. 1. Plasma free amino acids, adrenocortical activity, protein and nucleic acid content in the liver were studied in the hibernating, aroused and normothermic ground squirrel ( Citellus citellus). 2. 2. In the aroused animals tested after body temperature reached 36°C the level of plasma free amino acids was higher than in hibernating ones, as well as in normothermic controls studied in summer. The hibernation was linked with lowering of plasma free amino acids level in respect to the normothermic control. The only exception was found in cystine. 3. 3. Protein and RNA content in the liver were higher in aroused animals than in hibernating ones. Protein content was higher in aroused than in normothermic controls studied in summer. 4. 4. The level of 17-hydroxycorticosteroids (17-OHCS) in plasma was increased during the arousal; it was also higher in aroused in respect to the normothermic controls. 5. 5. Adrenal ascorbic acid concentration decrease during the arousal, being lower than in normothermic controls, as well.

Ethanol-ascorbate interrelationship in acute and chronic alcoholism in the guinea pig.

The effects of low (200 ppm) and of high (2000 ppm) ascorbic acid, in a nutritionally adequate diet, on blood ethanol levels have been studied in permanently carotid-cannulated, ethanol-infused, unanesthetized guinea pigs. In the acute study, the postinfusion rate of ethanol decline in the blood of animals treated with ascorbic acid was significantly higher when compared with animals treated with fructose, and the rate in the two treated groups was significantly higher than in untreated controls. In the chronic study, animals were infused with sublethal doses of ethanol (30% of the total caloric intake) for 8 weeks. Blood ethanol levels monitored throughout this period showed, at 3 hr postinfusion, a lower concentration in the group on a high ascorbic acid diet. Both experimental groups receiving ethanol lost significantly more body weight in the second week of dieting; but, while the group on high ascorbic acid regained weight steadily thereafter, the group on low ascorbic acid was still 50 g below the controls at the end of the experiment. Liver, kidney, and adrenal ascorbic acid concentrations were lower in the ethanol-treated groups compared to controls. Examination of the liver revealed more fatty metamorphosis or steatosis in the low ascorbic acid group, but there was no evidence of liver fibrosis or cirrhosis. These results demonstrate the feasibility of utilizing the guinea pig for the study of the biochemical and morphological sequelae of alcoholism. They further support the contention that a diet which is nutritionally adequate may no longer be so in the presence of high ethanol intake, and that supplemental vitamin C ingestion may afford protection against ethanol toxicity.

Endogenous corticosteroids and insulin in acute inflammation

Carrageenin-induced inflammatory responses in the hindpaws of rats were quantitated by measuring: (1) alterations in volumes of the paws; and (2) alterations in concentration of dye, previously injected intravenously, which was recovered in perfusates from the paws. The inflammatory response in one paw was attenuated by previously inducing an inflammatory response in the contralateral paw. The effect was abolished by pretreatment with insulin. Indexes of adrenal activity were increased after the induction of the inflammatory response and they were not attenuated by pretreatment with insulin. Adrenal hyperactivity was characterized by increased serum corticosterone concentration, decreased adrenal ascorbic acid content, and reduced number of circulating eosinophils. It is concluded that inflammatory stimuli which lead to alterations in microvessels depend on a facilitatory effect of insulin. This effect is antagonized by glucocorticoids released in enhanced concentrations after the application of noxious stimuli. Therefore, endogenous insulin and glucocorticoids act as modulators of inflammatory responses.

Adrenal response to crowding in the spiny field mouse, Mus platythrix (Bennett)

The role of the adrenal gland in response to crowding was examined in adult male spiny field mouse, Mus platythrix (Bennett), following a 7-day period of crowding at various population densities. The adrenal weight and adrenal total cholesterol concentration increased with reduction in floor area up to a population density of four animals per cage and declined thereafter. Adrenal ascorbic acid content gradually decreased with reduction in floor area. There was no significant variation in the serum cholesterol content in various groups. A probable role of these stimuli in the natural habitat is discussed in the light of observations made by R. K. Chandrahas (1974, Indian J. Med. Res. 62, 462–480).

Adrenal function and ascorbic acid concentrations in elderly women.

Tetracosactrin (Synacthen) tests were performed on 19 elderly women who had leucocyte ascorbic acid (LAA) levels of less than 15 microgram/108 WBC. 9 were then given a daily dose of 200 mg ascorbic acid orally for 2 weeks while the other 10 were left untreated. Following this, tetracosactrin tests were repeated in both groups. All initial plasm cortisol responses to tetracosactrin were within normal limits. Treatment with ascorbic acid produced no changes in these. This suggests that the low LAA levels often found in old people do not result in adrenal insufficiency.

Influence of Vitamin C Restriction on Guinea Pig Adrenal Calcium and Plasma Corticosteroids

Some aspects of adrenocortical function were investigated in young male guinea pigs fed an ascorbic acid (AsA)-deficient diet for 7 days, followed by 0.1 mg AsA/100 g body weight/day for 4 days; pair-fed guinea pigs served as controls. Ninety minutes prior to killine, all guinea pigs received either an adrenocorticotropic hormone (ACTH) or saline injection, and 30 minutes prior to killing, all were injected with 20 muCi 45Ca/100 g body weight intraperitoneally. AsA restriction alone caused an 89% reduction in adrenal AsA concentration, but growth rate, adrenal weight and plasma ACTH were not different from those of pair-fed controls. Adrenal radiocalcium uptake, adrenal calcium content and plasma corticosteroids were similar in saline-treated guinea pigs restricted in AsA and the ACTH-treated controls, all of which were significantly higher than the values observed in saline-injected controls. Similar responses of the ACTH-treated controls and the saline-treated mildly deficient guinea pigs indicated that, at the adrenal AsA levels achieved (4.45 to 7.02 mg/100 g tissue), adrenal calcium and plasma corticosteroids increased significantly without the mediation of ACTH.

Effects of Stress on the Corticosterone Content of the Blood Plasma and Adrenal Gland of Intact and Bursectomized Gallus Domesticus

The response of intact and bursectomized chicks to stressful stimuli has been examined. The stressors imposed were: a. fast-acting ACTH administration; b. immersion in cold water; c. starvation.In Bursa-intact chicks the results were as follows: 1. Plasma corticosterone was increased by all stimuli. 2. Adrenal corticosterone was decreased by ACTH treatment while it was increased by immersion in cold water and by starvation. 3. Plasma glucose was increased by ACTH administration and cold water immersion and decreased by starvation of the birds. 4. Adrenal ascorbic acid concentration was not influenced by all stimuli. 5. Adrenal weights were found to be increased by ACTH and starvation treatments only. 6. Bursa weights were increased by ACTH administration. 7. A very low concentration of corticosterone was found in the Bursa of Fabricius.Bursectomized chicks differed from the intact ones in the following: 1. Plasma and adrenal corticosterone concentrations were not increased by starvation. 2. Plasma glucose increased moderately with ACTH administration. 3. Adrenal ascorbic acid was depleted by all stimuli but was not related to the corticosterone level in the adrenals and blood plasma.

The effect of nicotine on ascorbic acid retention by guinea pigs.

Forty-eight male guinea pigs on an ascorbic acid free diet received daily oral injections of 2 mg L-ascorbic acid/100 g body weight for 2 weeks. Simultaneous injections of nicotine were given subcutaneously at 0.66 mg per animal per day; during the second week a second nicotine dose was administered 3 h later. On an equal weight basis each injection was approximately double the nicotine intake of a smoker of 40 cigarettes per day. On the last day at 1 h after a dose of L-ascorbic acid-1-14C there was more radioactivity and ascorbic acid remaining in the gastrointestinal tract contents of nicotine-treated animals than in saline-injected control animals. There were lower concentrations of L-ascorbic acid-1-14C in adrenals, brain, kidneys, and liver of nicotine-injected animals 1 h after the dose but higher concentrations 3, 6, and 12 h after the dose when compared to saline-injected animals. At all times adrenal and liver total ascorbic acid concentrations were higher in nicotine-treated animals. Brain and kidney concentrations showed a similar trend. The results indicate that there was delayed absorption of ascorbic acid in the presence of nicotine. Possible mechanisms of this effect are considered.

The Effect of Stress and Warfarin on the Adrenal Gland in Relation to Spontaneous Hemorrhage, as Judged by Measurement of Adrenal Ascorbic Acid and Serum Corticosterone

SummaryRats were subjected to the following procedures: No treatment, Stressor (10% NaCl i.p.), Warfarin for 7 days, Stressor followed by Warfarin; and groups were sacrificed at intervals for assessment of spontaneous hemorrhage and of adrenal ascorbic acid concentration. There was no hemorrhage in the no treatment and stressor groups; some hemorrhage in the warfarin group; profound hemorrhage with Warfarin + Stressor. The adrenal ascorbic acid concentration was found to be lower, 8 h and again 5 days after stress, and remained lower in the warfarin + stress animals. Warfarin had no effect on adrenal ascorbic acid level.In another series of experiments in which the stress consisted of an electric current to the cage floor for 6 sec over 15 min, rats were sacrificed daily for determination of serum corticosterone concentration and occurrence of spontaneous hemorrhage. There was a statistically significant increase of serum corticosterone concentration with stress, warfarin and combined warfarin and stress treatments (P< 0.001 for all three variables). There was a significant correlation (r = 0.96 and 0.89, P< 0.01) for serum corticosterone concentration with hemorrhage score and incidence of hemorrhage in stressed rats receiving warfarin, but not in those receiving only warfarin. The results indicate an activation, rather than an exhaustion, of the pituitary-adrenal axis during the combined action of anticoagulant and stress, which results in the development of spontaneous hemorrhage.

Influence of surgical and steroidal bursectomy on the behavior of adrenal ascorbic acid during stress in juvenile pigeons

The experimental response of adrenal ascorbic acid (AAA) to stress in juvenile pigeons was studied after surgical removal of the bursa of Fabricius and chronic administration of cortical and male sex hormone. Surgical bursectomy facilitated the depletion of AAA during stress. Corticoid therapy caused an involution of the bursa while AAA was unaltered after exposure to stress. Androgen administration did not regress the bursa, but stress evoked major depletions in AAA concentration. The probable mediation of androgen in precipitating these stress responses has been briefly discussed.

Ascorbic acid deficiency and pituitary adrenocortical activity in the guinea-pig.

1. Guinea-pigs kept on a diet deficient in ascorbic acid lost weight and became moribund in about 24 days.2. The adrenal ascorbic acid concentration fell rapidly during the first 2 weeks, and the plasma corticosteroid concentration and 17-oxogenic steroid excretion rose sharply in the third week of ascorbic acid deficiency.3. Both histamine and corticotrophin increased the plasma corticosteroid concentration when injected during the second week but failed to change the pre-existing high concentration of the steroid in the third week of ascorbic acid deficiency.4. The observations confirm that ascorbic acid is not involved in corticoidogenesis and that scurvy is a severe stress which increases adrenocortical activity to such an extent that the rate of synthesis of corticosteroids is incapable of matching the rate of their release.

The effect of 1-trans- Δ9-tetrahydrocannabinol on the hypothalamo-hypophyseal-adrenal axis of rats

1-trans- Δ 9-Tetrahydrocannabinol ( Δ 9-THC) was found to be a potent stimulator of ACTH secretion, as evidenced by depletion of adrena ascorbic acid in rats. Low doses of Δ 9-THC that were inactive in unanesthetized rats stimulated ACTH secretion in pentobarbital anesthetized rats. This observation differentiates Δ 9-THC from other drugs reported to stimulate ACTH secretion. A nonstimulating dose of Δ 9-THC did not block the secretion of ACTH induced by epinephrine. The concentration of adrenal ascorbic acid one hour after a fifth daily injection did not differ significantly from that observed after a single injection.

Effect of procine beta melanocyte-stimulating hormone on blood lymphocyte count and serum corticosterone concentration of the rabbit.

Beta MSH is known to lack lipolytic or corticotropic activity in the rat. In intact rabbits, the injection of 10–100 ng purified porcine β-MSH not only elevated serum free fatty acid (FFA) concentration 2 hr later, but also caused a reduction in blood lymphocyte count and a marked increase in serum corticosterone concentration. The effects of 10 and 100 ng (8-MSH on blood lymphocytes, serum FFA and serum corticosterone were similar in magnitude to those produced by 10 and 100 μg oxycellulose- purified ACTH. Lipolytic assays showed the ACTH preparation to be active on rat and hamster adipose tissues at a concentration of 0.01 μg/ml, and the β-MSH preparation to be inactive at 10 μg/ml. In the hypophysectomized rat 0.15 μg of the ACTH preparation depleted adrenal ascorbic acid content, while 500 Mg of the β-MSH preparation had no effect. Therefore, the β-MSH preparation contained less than 0.03% ACTH. These data suggest that β-MSH may possess substantial corticotropic activity in the rabbit. (Endocrinology 86: 1410, 1970)