Adrenal Ascorbate Research Articles

Scurvy induced changes and ascorbate defense in albino rats, Rattus norvegicus

An attempt has been made to find out effectiveness of scorbutogenic diet in albino rats, Rattus norvegicus. These animals received 50 and 80 gm cakes of scorbutogenic diet for 15 and 30 days respectively. No scurvy like symptoms were observed rather boils got appeared on their hind limbs, below ear and neck region. Steroid producing glands indicated enhanced steroidogenesis as evidenced by decreased concentrations of adrenal ascorbate and cholesterol. The results suggested that scorbutogenic diet was ineffective to cause scurvy in this species.

Panorganismal Gut Microbiome−Host Metabolic Crosstalk

Coevolution shapes interorganismal crosstalk leading to profound and diverse cellular and metabolic changes as observed in gut dysbiosis in human diseases. Here, we modulated a simplified gut microbiota using pro-, pre-, and synbiotics to assess the depth of systemic metabolic exchanges in mice, using a multicompartmental modeling approach with metabolic signatures from 10 tissue/fluid compartments. The nutritionally induced microbial changes modulated host lipid, carbohydrate, and amino acid metabolism at a panorganismal scale. Galactosyl-oligosaccharides reduced lipogenesis, triacylglycerol incorporation into lipoproteins and triglyceride concentration in the liver and the kidney. Those changes were not correlated with decreased plasma lipoproteins that were specifically induced by L. rhamnosus supplementation. Additional alteration of transmethylation metabolic pathways (homocysteine-betaine) was observed in the liver and the pancreas following pre- and synbiotic microbial modulation, which may be of interest for control of glucose metabolism and insulin sensitivity. Probiotics also reduced hepatic glycogen and glutamine and adrenal ascorbate with inferred effects on energy homeostasis, antioxidation, and steroidogenesis. These studies show the breadth and the depth of gut microbiome modulations of host biochemistry and reveal that major mammalian metabolic processes are under symbiotic homeostatic control.

Hypersensitivity of spontaneously hypertensive rats to heat and ether before the onset of high blood pressure.

Hypertension-prone, male, spontaneously hypertensive rats (SHR; n = 60) and normotensive, male, Sprague-Dawley rats (S-D; n = 60) were exposed to the relatively innocuous stimulus of heat and ether when they were 40 days of age, just before the usual onset of high blood pressure in SHR. The animals were decapitated 0, 2, 5, 15, and 60 min postexposure to heat and ether. Blood levels of corticosterone, aldosterone, PRL, GH were measured concomitant with pituitary content of GH and PRL and adrenal content of ascorbic acid and cholesterol. The foregoing constituents were used as an index of pituitary-adrenal responsiveness. Changes in circulating corticosterone, PRL, GH, and especially aldosterone indicated that before the onset of their high blood pressure, SHR are much more responsive to noxious stimuli than normotensive S-D. The pattern of change in the pituitary content of GH and PRL, adrenal ascorbate, and cholesterol were also indicative of SHR hypersensitivity. These findings suggest that adrenal steroidogenesis and the stress response pattern in SHR vs. normotensive rats may be unique.

Stability of the Third International Standard for corticotrophin: accelerated degradation study using different bioassays and isoelectric focusing.

The corticotrophin activity of ampoules of the Third International Standard for Corticotrophin (IS) kept at 20 and 37 °C for 15 years was compared with that of ampoules of the IS stored under normal conditions (−20 °C in the dark), using adrenal ascorbate depletion assays after subcutaneous administration of the hormone, assays of an increase in plasma corticosterone after intravenous administration of the hormone and in-vitro adrenal cell corticosterone production assays. Estimates of activity by all three methods are homogeneous and give combined weighted geometric means (with 95% confidence limits), as per cent of the activity in the IS stored at −20 °C, of 92·1 (84·8–100) and 77·8 (71·6–84·5) for the 20 and 37 °C degradation samples respectively. Isoelectric focusing studies of the ampoule contents of the three preparations showed that ampoules of the IS stored at 20 and 37 °C contained 90 and 79% respectively, of the component representing native corticotrophin found in the IS. These estimates of corticotrophin content are comparable to the estimates of biological activity of these preparations. The stability of the IS was calculated from the combined bioassay data assuming that degradation follows first order kinetics. The predicted half-life for the activity of the IS is 2800 years with an approximate lower 95% confidence limit of 500 years; the predicted activity of the IS remaining now, after 20 years at −20 °C, is 99·5% of the original activity with an approximate lower 95% confidence limit of 97·3%

Ascorbic acid transport by isolated bovine adrenal cortical cells.

Viable, ACTH-sensitive, bovine adrenal cortical cells have the ability to accumulate [1-14C]ascorbic acid. Transport of the vitamin displays saturation kinetics (Km = 16.6 microM), requires Ca2+, and is inhibited maximally by ACTH at the same concentrations of the hormone necessary for maximal stimulation of steroidogenesis. Despite the transport of quantities of radioactive ascorbate amounting to approximately 25% of the total intracellular pool, no change in the ascorbate concentration in the cells can be detected by chemical methods. Transport of the vitamin is apparently a membrane carrier-mediated exchange process, since although intracellular ascorbate concentrations are 60- to 90-fold higher than those in the incubation medium, accumulated label can only be displaced when the cells are incubated in the presence of unlabeled ascorbic acid or metabolic inhibitors. Furthermore, ACTH fails to deplete ascorbic acid from [1-14C]ascorbate-loaded cells. It is hypothesized that the vitamin exists in two pools only one of which can be depleted by ACTH. This ACTH-depletable pool is no longer present in the isolated cell. In fact, as much as 66% of the ascorbic acid is lost from rat adrenals incubated for 15 min post adrenalectomy. The remaining pool of adrenal ascorbate is not depleted by ACTH and is also maintained against a concentration gradient.

Ascorbate metabolism in swine. Influence of maternal hypoxia on fetal tissue ascorbate levels.

The effects of birth on tissue and serum ascorbate levels as well as the influence of maternal hypoxia on fetal tissue and serum ascorbate levels were investigated. Serum and adrenal ascorbate levels in neonatal swine were drastically decreased when compared with near-term (112-day-old) fetal swine. Kidney, cardiac, and muscle ascorbate levels also were found to be decreased on birth although liver levels in the newborn rose significantly above fetal levels. Hypoxic stress produced by decreasing the oxygen concentration in the maternal gas supply produced effects in 112-day-old fetal pigs which were similar to those noted for birth. An hypothesis was presented to explain the observation in which it was suggested that ascorbate may have a key role in the mechanism by which the fetal pig successfully coped with the stress of birth.

Adrenal Gland in Vitamin E Deficiency: LIPID PEROXIDATION AND MALONALDEHYDE PRODUCTION IN VITRO

Abstract Incubation of adrenal homogenates of tocopherol-deficient rats was shown to produce a compound which was identified as malonaldehyde. This product formed a pink color with thiobarbituric acid (TBA) which had the same absorption characteristics as authentic malonaldehyde-TBA complex. The malonaldehyde production in vitro as an index of lipid peroxidation, as tested by the TBA test, has been evaluated and compared in the various tissue homogenates of tocopherol-deficient and control rats. Lipid peroxidation in the liver homogenates of tocopherol-deficient rats reached a maximum level in 1 week. In contrast, the adrenal homogenates exhibited a progressive increase in lipid peroxidation in vitro from the 2nd to 7th week of tocopherol deprivation. The kinetic studies of lipid peroxidation reaction of adrenal homogenate during various stages of vitamin E deprivation indicated presence of a lag period in the early period of tocopherol deprivation which disappeared by 9th week of tocopherol deprivation. The extent of adrenal lipid peroxidation in vitro was about 10 times higher than in any other tissue tested. Diminution of adrenal ascorbate in the deficient group by stress, dialysis of the homogenate, or addition of ascorbic acid oxidase to the homogenate reduced lipid peroxidation in vitro. Malonaldehyde was not produced by either the particulate nor the supernatant fraction of the adrenal homogenate, but optimal amounts were formed by combining these two fractions. The ability of the supernantant fraction to catalyze formation of malonaldehyde (in the presence of adrenal particulate fraction) could be mimicked by ascorbic acid; this catalytic effect was abolished by addition of ascorbic acid oxidase. The content of adrenal ascorbate and percentage of individual fatty acids were similar in the two dietary groups at various stages of vitamin E deprivation. It is suggested that with gradual diminution of tocopherol, the high level of polyunsaturated lipids in the adrenal particulate matter, in the presence of high ascorbic acid in the adrenal supernatant solution, may contribute to the high lipid peroxidation in vitro in vitamin E-deficient rats.

Multiple action of 2′-diethylaminoethyl 2,2-diphenylpentanoate HCl (SKF 525-A) on rat liver tryptophan pyrrolase in vivo

SKF 525-A was observed to have an early stimulatory action in vivo on liver tryptophan pyrrolase activity in intact or adrenalectomized, but not hypophysectomized, male adult rats. The stimulatory effect was abolished by co-administration of actinomycin D, puromycin, or cycloheximide in intact animals, suggesting that SKF 525-A was inducing de novo formation of apo-tryptophan pyrrolase. Concurrent with stimulation of tryptophan pyrrolase in intact animals by SKF 525-A, there was a significant decrease in adrenal ascorbate. These effects of SKF 525-A on tryptophan pyrrolase or adrenal ascorbate were not seen in hypophysectomized rats. The stimulation of tryptophan pyrrolase activity by SKF 525-A would therefore seem to involve some form of pituitary activation. When SKF 525-A was co-administered with hydrocortisone, the stimulatory effects of the two agents were merely additive. However, administration of SKF 525-A to adrenalectomized rats receiving repeated injections of hydrocortisone markedly potentiated the inducing action of hydrocortisone. This enhancement of hydrocortisone induction occurred only if SKF 525-A was administered during the early tryptophan pyrrolase induction phase, i.e. prior to development of attenuation of hydrocortisone induction. Such an effect of SKF 525-A was not obtained in hypophysectomized rats undergoing similar treatments. SKF 525-A-like enhancement of hydrocortisone-induced tryptophan pyrrolase increases could also be produced by injection of saline homogenates of rat pituitary glands during the early tryptophan pyrrolase induction phase. Animals pretreated 12 hr before with SKF 525-A showed a reduced capacity to form new tryptophan pyrrolase after hydrocortisone administration. This late “anti-induc-tive” action of SKF 525-A was also seen for a second “stimulatory” dose of SKF 525-A but was not present for substrate stimulation of tryptophan pyrrolase (caused by injected tryptophan). These latter data indicate that SKF 525-A may reduce the ability of the liver to produce tryptophan pyrrolase from other than pre-existing mRNA template. It is concluded that SKF 525-A effects on hepatic tryptophan pyrrolase are multiple, ranging from hydrocortisone-like to actinomycin-like. No simple explanation for such diverse activities can be offered but this should serve as a caution to investigators who regard SKF 525-A as pharmacologically inert (Mannering, Ann. N.Y. Acad. Sci., 123, 108 (1965); Brodie et al., Science 148, 1547 (1965) or as a specific inhibitor of microsomal enzyme systems in liver.

Adrenal ascorbic acid levels during pregnancy and lactation in rats and mice.

Adrenal ascorbate was determined in rats and mice at various stages of pregnancy and lactation. In rats the ascorbate was reduced throughout pregnancy and during the first 4 days of lactation, after which the level of the vitamin returned to normal. In mice a rise in adrenal ascorbate was evidenced on the 12th day of pregnancy and on the 1st day of lactation, whereas a significant reduction occurred on the 2nd day of lactation. After the 5th day of lactation the adrenal ascorbate returned to a normal level. These data are interpreted to mean that adrenal ascorbate reflects increased adrenocortical activity immediately after parturition and at the initiation of lactation. The authors are of the opinion that the return of adrenal ascorbate to a normal level by the 6th day of lactation does not necessarily mean that adrenocortical function has returned to the level of nonpregnant, nonlactating animals.

Influence of sulfhydryl compounds on in vitro steroid production by the rat adrenal gland.

ALTHOUGH there have been numerous reports on the effects of adrenal-L ectomy, adrenocorticotropic hormone and cortical steroids upon blood and tissue sulfhydryl levels (Binet and Poutonnet, 1943; Hess et al., 1951; Goldzieher et al., 1953a; Goldzieher et al, 1953b), the effect of sulfhydryl and disulfide compounds upon corticoid output has been little studied. Carey et al. (1951) reported that large doses of glutathione depleted rat and guinea pig adrenal ascorbic acid and cholesterol. Bacq et at. (1953) demonstrated a large fall in adrenal ascorbate after administration of 2-aminoethanethiol (cysteamine) but no change in cholesterol content. Goldzieher and Edlin (1953) found a fall in urinary 17-keto and reducing steriods after prolonged treatment with cystine. The purpose of the present study was to observe the effect of a number of sulfur compounds and sulfhydryl-binding inhibitors upon the in vitro formaldehydogenic steroid output of rat adrenal glands.