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PubMed2001

Effect of dexamethasone on adipocyte differentiation markers and tumour necrosis factor-alpha expression in human PAZ6 cells.

AIMS/HYPOTHESIS: Adipose tissue-derived tumour necrosis factor-alpha (TNF-alpha) has been implicated in the insulin resistance observed in animal models of obesity. Moreover, TNF-alpha has inhibitory effects on adipocyte differentiation. Glucocorticoids play important roles in the regulation of insulin sensitivity and adipose tissue distribution. We therefore studied the effect of dexamethasone on TNF-alpha expression and adipocyte differentiation in human PAZ6 cells. METHODS: The expression of TNF-alpha and adipocyte differentiation markers was assessed by reverse-transcription polymerase chain reaction in PAZ6 cells. RESULTS: In cells cultured for 15 days in the presence of dexamethasone, adipocyte differentiation marker expression was higher and TNF-alpha expression was lower than in cells cultured in the absence of dexamethasone. The presence of dexamethasone was necessary during the whole period of differentiation because removal of dexamethasone during the second week resulted in poorly differentiated adipocytes that express higher levels of TNF-alpha. Dexamethasone also reduced TNF-alpha expression during early stages of differentiation. The use of a TNF-alpha-neutralising antibody showed, however, that endogenously-produced TNF-alpha did not play an important part in the control of PAZ6 cell differentiation. During early stages of adipocyte differentiation, dexamethasone induced the expression of the transcription factors PPAR gamma (peroxisome proliferator activated receptor gamma) and C/EBP alpha (CCAAT/enhancer binding protein alpha) while inhibiting the expression of the inhibitor of DNA binding Id2. CONCLUSION/INTERPRETATION: The effect of dexamethasone on human adipocyte differentiation is not mediated by reduction of TNF-alpha expression but more likely by regulation of the expression of nuclear factors such as PPAR gamma, CEBP alpha and Id2.

Adipocytes↗
PubMedDate not supplied

Effect of dexamethasone therapy on the neonatal ductus arteriosus.

Patent ductus arteriosus (PDA) is believed to be a contributing factor in the etiopathogenesis of bronchopulmonary dysplasia (BPD). We studied the effects of early dexamethasone therapy on persistent ductal patency and the role of PDA in the etiopathogenesis of BPD during the course of a randomized double-blind trial of dexamethasone to prevent BPD. Infants, who weighed between 700 and 999 g, had severe RDS, and had been given surfactant, were randomized to receive a 12-day course of dexamethasone (n = 13) or placebo (n = 17) starting within the first 12 hours of postnatal life. The diagnosis of PDA was made clinically and was confirmed by cardiac ultrasound. The incidence of clinically significant ductus in infants who weighed less than 1000 g was 23% in the dexamethasone-treated group, as compared with 59% in infants who were given placebo. This difference was marginally significant, p = 0.05, odds ratio 0.21, 95% confidence interval 0.04-1.05. None of the infants in the dexamethasone group had recurrence of PDA after indomethacin therapy as compared with three infants in the placebo group. Dexamethasone significantly reduced the number of days infants required ventilator and supplemental oxygen as compared with infants who received placebo. Dexamethasone, as compared with placebo, also reduced the incidence of BPD, p = 0.025, odds ratio 0.08, 95% confidence interval 0.01-0.58. Dexamethasone may reduce the incidence of PDA in premature infants who weigh less than 1000 g at birth and thereby reduce the incidence of BPD.

Anti-Inflammatory Agents↗
PubMed2001

The effect of dexamethasone on respirator-dependent very-low-birth-weight infants is best predicted by chest X-ray.

BACKGROUND: Chronic lung disease (CLD) in premature infants shows a variable clinical course with different radiological manifestations. OBJECTIVE: To evaluate the correlation between parameters of trans-membrane permeability [albumin/secretory component (SC)] and oxidative stress [malondialdehyde (MDA)/SC] in tracheal aspirate fluid (TAF) and radiological findings with the effect of a 5-day course of dexamethasone (0.5 mg/kg per day). MATERIALS AND METHODS: Fifty ventilator-dependent premature infants with birth weights < 1,500 g (gestational ages 23-31 weeks) and radiological signs of early chronic lung disease (CLD) were treated with dexamethasone at day of life 5-27 (median 10 days) because of respiratory deterioration. TAF was collected serially. Chest X-rays taken before and 8-10 days after dexamethasone were scored for changes of opacification, consolidation and hyperinflation/emphysema, and classified into three groups. RESULTS: Twenty-four infants had a positive response to dexamethasone, defined as a reduction of the ventilation index FiO2 x mean airway pressure > 40% at day 5, compared to pretreatment values. About 80% of the responders showed homogeneous lung opacification on chest X-ray, reflecting leaky lung syndrome. In contrast, seven of eight infants with predominantly emphysema on radiology were non-responders; 80% of infants with a mixed radiological picture characterized by predominance of consolidations alternating with regions of emphysema were also non-responders. Ratios of albumin/SC and MDA/SC in TAF decreased significantly within 3 days after the onset of dexamethasone. However, MDA/SC was persistently higher in non-responders compared to responders. Opaque lungs were largely improved by dexamethasone, in contrast to streaky or patchy consolidations and emphysema. In a logistic regression model, radiographic classification was the most important factor influencing the response to dexamethasone with a positive predictive value of 86%, followed by albumin/SC ratio. CONCLUSIONS: The optimum timing of dexamethasone treatment may be determined by the stage of developing CLD and radiological findings rather than by the age of the premature infant.

Albumins↗
PubMed2004

Dexamethasone as a probe for docetaxel clearance.

PURPOSE: A pilot study was conducted in 23 patients in order to assess the correlation between docetaxel clearance (CL) and pharmacokinetics of dexamethasone. Dexamethasone is mainly 6-beta hydroxylated by CYP3A4, and is regularly used as standard docetaxel premedication. Genotyping of known functional single nucleotide polymorphism (SNP) of CYP3A5 (G22893A) and mdr-1 (G2677T, G2677A, and C3435T) have been performed in order to tentatively correlate genotype with docetaxel and dexamethasone pharmacokinetics. PATIENTS AND METHODS: To be eligible for this study, patients were required to have a solid malignancy for which docetaxel was indicated. A population pharmacokinetic approach was used to determine individual pharmacokinetic parameters of both docetaxel and dexamethasone by Bayesian analysis, and to screen relationships between docetaxel CL and patients' demographic, phenotype and genotype covariates. RESULTS: Three different pharmacokinetic parameters of dexamethasone were significantly correlated with docetaxel CL: dexamethasone plasma clearance (DPC) that ranged between 7.7 and 27.2 l/h, urinary amount of 6beta-hydroxydexamethasone, and the ratio between urinary amount of 6beta-hydroxydexamethasone and unchanged dexamethasone. The best covariate model was docetaxel CL (l/h) = 356 x fu(alpha1-AG) x (1-0.17 x HPMT)(1+0.126 x DPC) where fu(alpha1-AG) is the unbound plasma fraction of docetaxel calculated from alpha1-acid glycoprotein plasma level, and HPMT is hepatic metastasis coded as 1 if present or 0 if absent. No significant difference in docetaxel CL was observed between the several genotypes. CONCLUSIONS: Dexamethasone may be used as a probe to predict docetaxel clearances, hence reducing interindividual variability.

Adult↗
PubMed2001

Changes of cerebral blood flow following dexamethasone treatment in brain tumour patients. A Xe/CT study.

BACKGROUND: It is not exactly known how dexamethasone improves the function of brain that is affected by tumour. Whether and in what sense dexamethasone influences cerebral blood flow has rarely been addressed and previous investigations have yielded inconsistent results. METHOD: Stable xenon-enhanced computed tomography (Xe/CT) was used to assess the regional cerebral blood flow (rCBF) in 67 patients with supratentorial primary and secondary brain tumours. rCBF studies were done at least once prior to resection or stereotactic biopsy of the tumours. In nine patients repeated studies before surgery and in 15 patients additional studies after resective surgery were obtained. Dexamethasone was administered according to the clinical needs before surgery and systematically after surgery. Of the preoperative studies 30 were obtained before and 47 during dexamethasone treatment. The rCBF data were analysed upon correlations with daily dose, cumulative dose, and duration of dexamethasone treatment. Moreover, individual courses before and after surgery were examined. FINDINGS: Mainly inverse correlations were found between the treatment parameters, particularly the daily dose of dexamethasone, and rCBF. Only in the subgroup of glioblastoma patients, a positive correlation was found of both duration and cumulative dose of dexamethasone with rCBF in oedema. Serial observations of individual patients confirmed the above findings, yet with possible exceptions. After tumour resection a clear improvement of rCBF was regularly observed. INTERPRETATION: The beneficial effect of dexamethasone is not attributed to an increase of cerebral blood flow, because rather decreases of rCBF are mostly observed.

Adult↗
PubMed1992

Synergistic effects of dexamethasone on platelet-derived growth factor mitogenesis in vitro.

Platelet-derived growth factor (PDGF) and insulin-like growth factor-I (IGF-I) interact to stimulate proliferation of fibroblasts in culture. Glucocorticoids variably effect the response of cultured fibroblasts to polypeptide growth factors. This study determined the effects of dexamethasone on growth-factor stimulation of gingival, periodontal ligament and pulp fibroblast proliferation in vitro. Cultures of quiescent, low-passage, human fibroblasts were treated for varying periods of time with transforming growth factor-beta 2 (TGF-beta 2), PDGF and IGF-I: (1) alone, (2) in combination with each other, (3) singly plus dexamethasone, (4) in combination plus dexamethasone. Combinations of human, recombinant PDGF and IGF-I (10-1000 ng/ml) induced significantly higher rates of cell proliferation than either factor alone. Dexamethasone at doses ranging from 10(-5) to 10(-8) M substantially enhanced cell proliferation induced by these combinations and by PDGF without IGF-I but not IGF-I alone. By 6 days after a single application, 2-3 times as many cells were present in the PDGF and dexamethasone cultures as compared to PDGF without IGF-I. TGF-beta 2 specifically blocked the effects of dexamethasone added to PDGF-stimulated cells. Collagen and non-collagenous protein synthesis was not affected by the addition of PDGF and IGF-I with or without dexamethasone. These data suggest that dexamethasone may substitute for IGF-I in PDGF stimulation of cell proliferation.

Cell Division↗
PubMed1987

Effect of dexamethasone on cytochrome P-450 mediated metabolism of 2-acetylaminofluorene in cultured rat hepatocytes.

The metabolism of 2-acetylaminofluorene (AAF) to its six oxidative metabolites has been used to investigate the effect of dexamethasone on cytochrome P-450 activity in cultured rat hepatocytes. In control hepatocytes the metabolism of AAF to its 1-, 5-, 7-, 9- and N-hydroxylated metabolites rapidly declined in culture over the first 24 hr while 3-hydroxylation remained relatively constant. These activities either remained unchanged or increased slightly during the next 48 hr in culture. The addition of dexamethasone (100 nM) to the culture medium had little effect in arresting the initial decline but by 72 hr the 7-, 5- and 3-hydroxylations increased to values 2.5, 16 and 21 times the respective 24-hr values. The inductive effect of dexamethasone on the 3- and 5-hydroxylations of AAF was maximal at 100 nM whereas the 7-hydroxylation increased linearly as a function of the dexamethasone concentration up to 1 microM. Cortisol and corticosterone and the non-glucocorticoids fluoxymesterone and methyltestosterone induced a pattern of AAF metabolism resembling that in dexamethasone-treated cultures, suggesting that a range of steroids not restricted to glucocorticoids may induce multiple cytochrome P-450 isozymes via related mechanisms. Pregnenolone 16 alpha-carbonitrile induced only the 7-hydroxylation of AAF probably reflecting induction of cytochrome P-450p. While dexamethasone was a strong inducer of the 3- and 5-hydroxylations of AAF in hepatocyte culture, assay of these activities in freshly isolated cells after in vivo treatment with dexamethasone showed a strong induction of 7-hydroxylation but only small effects on 3- and 5-hydroxylations. Indeed the profile of AAF metabolism induced in culture by dexamethasone resembles more closely the profile induced by 3-methylcholanthrene in vivo. These data suggest that factors yet to be identified strongly influence the steroid-induced pattern of cytochrome P-450 gene expression.

2-Acetylaminofluorene↗
PubMed1988

Modulation of collagen metabolism by glucocorticoids. Receptor-mediated effects of dexamethasone on collagen biosynthesis in chick embryo fibroblasts and chondrocytes.

The steroid modulation of collagen metabolism was studied by injecting chick embryos with dexamethasone in vivo, and collagen synthesis was subsequently assayed by pulse-labeling the tissue with [14C]proline in vitro. The synthesis of [14C]hydroxyproline in tendons and sterna from chick embryos treated with dexamethasone was markedly reduced as compared with untreated controls. The inhibition of [3H]hydroxyproline synthesis was accompanied by a similar reduction in type I and II procollagen mRNA levels, as detected by Northern blot and dot blot hybridizations with chick pro alpha 1(I), pro alpha 2(I) and pro alpha 1(II) sequence specific cDNAs. The reduction in type II procollagen mRNA level was shown to be dose dependent. Control experiments indicated that the post-translational hydroxylation of prolyl residues was only slightly decreased in dexamethasone treated animals, and that the specific activity of the intracellular free proline pool and the intracellular degradation of collagen were unchanged. To address the mechanisms of the inhibition of collagen biosynthesis, specific binding of dexamethasone to glucocorticoid receptors in chick embryo tendon and cartilage cells was studied in a whole cell assay using [3H]dexamethasone as the ligand. Matrix-free tendon and cartilage cells had approximately 19,000 and 15,000 receptor sites per cell, respectively, and the binding affinities (Kd) for dexamethasone in tendon and cartilage cells were 2.9 x 10(-9) and 2.3 x 10(-9) M. Comparable values were obtained using a cytosol binding assay. The nuclear binding of dexamethasone in tendon and cartilage cells were similar. The results suggest that the dexamethasone-induced inhibition of collagen production is primarily due to decreased levels of functional procollagen mRNA, possibly resulting from receptor-mediated inhibition of the gene expression on the transcriptional level.

Animals↗
PubMed1993

Dexamethasone treatment fails to reduce oxygen-induced lung injury in the preterm guinea pig. Effects on pulmonary inflammation and antioxidant status.

Dexamethasone (10 mg/kg/day) or vehicle was administered in a randomized, controlled fashion to 3-day preterm guinea pigs exposed to either 21% oxygen or 95% oxygen for 72 hr and maintained in room air for a further 96 hr. Treatment with dexamethasone had no effect on survival of preterm pups maintained in either 21% or 95% O2. Dexamethasone treatment reduced the growth rate of pups, the effect occurring earlier (0-3 days) in 21% O2-treated pups than in 95% O2-treated pups (5-7 days). Exposure to 95% O2 reduced the survival rate of preterm animals (73% vs 100%, P < 0.05). Surviving pups developed acute lung injury, characterized by the accumulation of a protein-rich exudate in the alveoli and an infiltration of inflammatory cells, particularly neutrophils into the lung. Dexamethasone treatment attenuated the pulmonary inflammatory cell infiltration, in particular neutrophils, both during oxygen exposure (16.4 x 10(4) vs 9.4 x 10(4)/mL; P < 0.05) and following return to ambient conditions (28.0 x 10(4) vs 5.1 x 10(4)/mL; P < 0.05). Elastase activity in bronchoalveolar lavage fluid, which was primarily of neutrophil origin, was unchanged by dexamethasone treatment. Dexamethasone-treated pups had increased pulmonary antioxidant enzyme activities (Cu/Zn-superoxide dismutase; Mn-superoxide dismutase, catalase and glutathione peroxidase) during recovery from oxidative injury. Although there was both a marked reduction in numbers of neutrophils in the lung and elevated pulmonary antioxidant enzyme activities in dexamethasone-treated pups, the degree of microvascular permeability, as determined by both the lung wet weight/dry weight ratio and the presence of plasma proteins in the lavage fluid, was unchanged. Combined, these results imply that dexamethasone, although capable of blunting the influx of neutrophils to the hyperoxia-exposed lung and inducing antioxidant defences in the immature lung, cannot modify the progression of acute oxygen-induced injury of the immature lung.

Amino Acid Sequence↗
PubMed1988

Cortisol suppression per nanogram per milliliter of plasma dexamethasone in depressive and normal subjects.

It has been suggested that dexamethasone pharmacokinetics may affect cortisol suppression during the Dexamethasone Suppression Test (DST). In depressed patients the cortisol response has been shown to negatively correlate with dexamethasone plasma concentrations, which also influence the sensitivity and specificity of the DST. These findings have been interpreted as weakening the utility of the DST. However, the analysis of pre- and post-1 mg DST cortisol concentrations corrected for plasma dexamethasone concentrations suggest that compared with normals (n = 52), patients with major depressive disorder (MDD) as a group (n = 71) had less suppressibility of cortisol to the same plasma dexamethasone concentrations. Moreover, when the MDD patients were evaluated based on DST status, the suppressors had cortisol/dexamethasone ratios (micrograms/dl of cortisol per ng/ml of plasma dexamethasone) similar to the normal controls, whereas the nonsuppressors had ratios that were significantly higher. These data suggest that DST non-suppression, as well as sensitivity and specificity of the DST in depression, is not only attributable to altered dexamethasone disposition, but indeed, there is a genuine reduced sensitivity of cortisol to dexamethasone that still points to an abnormality of the delayed feedback mechanism of the hypothalamic-pituitary-adrenal system in some depressed patients.

Adult↗
PubMed1983

Effects of dexamethasone and other glucocorticoid steroids on tyrosine hydroxylase activity in the superior cervical ganglion.

Dexamethasone is known to elicit an increase of tyrosine hydroxylase activity in the superior cervical ganglion. The details of such a glucocorticoid effect were investigated in the present study. Of 4 glucocorticoids (dexamethasone, corticosterone, hydrocortisone and triamcinolone) examined in rats, only the synthetic steroid dexamethasone was found to be effective in increasing ganglionic tyrosine hydroxylase activity (by 50% at 48 h after drug administration). Corticosterone even at doses as high as 50 mg/kg failed to show an effect. Since recent reports indicate that a cytoplasmic glucocorticoid receptor is not present in the sympathetic ganglion, it is unlikely that the dexamethasone effect involves a receptor-mediated mechanism. Moreover, the dexamethasone effect was totally blocked by chlorisondamine, a nicotinic cholinergic receptor antagonist. The possibility of an enhanced impulse flow from the CNS, however, was excluded by the finding that decentralization immediately prior to dexamethasone administration did not prevent the increase of ganglionic tyrosine hydroxylase activity, although earlier decentralization (24 h or longer) abolished the steroid effect. Significantly, in the freshly decentralized ganglia, the increase of tyrosine hydroxylase activity by dexamethasone was still blocked by chlorisondamine. Since synaptic activity in terminals is known to continue for a brief period following nerve transection, our data support the contention that the primary site of the dexamethasone effect may be the preganglionic terminals.

Animals↗
PubMed1993

Corticosterone is a preferable ligand for measuring rat brain corticosteroid receptors: competition by RU 28362 and RU 26752 for dexamethasone binding in rat hippocampal cytosol.

It is unclear whether in vitro corticosteroid receptor binding assays have used inappropriately high concentrations of synthetic corticosteroid competitors, thereby potentially introducing error into estimates of type I (mineralocorticoid) and type II (glucocorticoid) receptor binding. To determine more accurately the concentration of blockers necessary to discriminate between these two sites, we have derived Ki values for the competition of dexamethasone, RU 28362 and RU 26752 for [3H]corticosterone and [3H]dexamethasone binding in rat hippocampus. Non-specific binding of both radioligands was defined with unlabeled dexamethasone to exclude transcortin. The type II agonist RU 28362 competed for only a portion of [3H]corticosterone binding, exhibiting a Ki of 0.5 nM for this binding. In contrast, RU 28362 fully competed all binding of a saturating concentration of [3H]dexamethasone, even though [3H]dexamethasone also recognized type I receptors, defined as specific [3H]corticosterone binding in the presence of 80 nM RU 28362. RU 28362 competition for [3H]dexamethasone binding exhibited characteristics of a 2-site interaction, with Kis of 0.3 and 194 nM. The type I receptor antagonist RU 26752 competed less effectively for [3H]corticosterone and [3H]dexamethasone binding, but nonetheless competed fully within a 1000-fold concentration range. Even at a level less than 125 x its Ki for type I binding, RU 26752 still inhibited virtually all type II receptor binding by [3H]corticosterone. We conclude that type I and II receptors in rat brain are best distinguished using [3H]corticosterone as the labelling ligand, with cold RU 28362 and dexamethasone to eliminate binding to type II and transcortin sites, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Androstanols↗
PubMed1990

Determination of the capacity for proliferation and differentiation of osteoprogenitor cells in the presence and absence of dexamethasone.

Osteoprogenitor cells present in single-cell suspensions prepared from fetal rat calvaria (RC) form discrete mineralized three-dimensional bone nodules when cultured long-term in the presence of ascorbic acid and beta-glycerophosphate. These cells (CFU-O) constitute less than 1% of the total cell population under standard culture conditions and their number is increased in the presence of dexamethasone. Using the formation of the bone nodule as a marker for CFU-O, we have now analyzed the proliferation and differentiation capacity of these CFU-O by redistribution and continuous subculture experiments in the presence and absence of dexamethasone. Cell redistribution experiments showed no increase in nodule number after one population doubling with either treatment. After 5.4 population doublings of the entire RC population, nodule number increased up to 2.0-fold in control cultures and 4.5-fold in cultures containing 10 nM dexamethasone. Continuous subculture experiments in which cultures were split 1:3 every 3 day for up to seven subcultures showed that nodule number decreased in parallel with the split ratio in the absence of dexamethasone, while with dexamethasone nodule number was elevated above the number present in primary cultures for 1 or 2 subcultures after which nodule number decreased with the split ratio. Bone nodules were present for up to 18 population doublings. Measurements of nodule area by automated image analysis showed that dexamethasone increased nodule size and that nodule size decreased from primary to 1st to 2nd subculture with or without dexamethasone. The data suggest that dexamethasone selectively stimulates the proliferation of osteoprogenitor cells and that these progenitor cells have a limited capacity for generating daughter cells capable of expressing the bone phenotype.

Animals↗
PubMed1995

Dexamethasone influences intimal thickening and vascular reactivity in the rabbit collared carotid artery.

Intimal thickening predisposes to atherosclerosis and is often associated with alterations of the vascular reactivity of the artery. We investigated whether dexamethasone inhibited the intimal thickening and reactivity changes induced by a silicone collar placed around the left rabbit carotid artery for 2 weeks. The sham-operated, right artery served as control. Dexamethasone (1 mg/kg/day), given in the drinking water (n = 10) or by a subcutaneous minipump (n = 10), abolished intimal thickening compared to that of both placebo groups (n = 10). Both dexamethasone and the collar suppressed the isometric force development of isolated segments elicited by KCl in organ chamber experiments. The collar raised the sensitivity to serotonin (5-hydroxytryptamine, 5-HT) and the maximum force development (Emax) after normalization for the KCl responses. Dexamethasone exerted complex effects on 5-HT contractions in sham arteries: the curves often became biphasic, and sensitivity and Emax of the first phase were depressed by dexamethasone. In contrast, dexamethasone raised the hypersensitivity of collared arteries to 5-HT even further. Collar and dexamethasone did not influence endothelium-dependent relaxations elicited by acetylcholine or the calcium ionophore A-23187. It is concluded that dexamethasone interfered with neo-intima formation in the collar model, presumably by inhibition of smooth muscle cell migration and/or proliferation, without restoring contractile behaviour. Therefore, the collar-induced alterations in the reactivity of the smooth muscle cells in the media appear to be unrelated to the process of intimal thickening.

Animals↗
PubMed1984

Induction of acute phase proteins by dexamethasone in rat hepatocyte primary cultures.

The effect of dexamethasone on the synthesis of acute phase proteins has been studied in primary cultures of rat hepatocytes. In the absence of dexamethasone no detectable amounts of alpha 2-macroglobulin were synthesized by hepatocytes cultured for 1 day. alpha 2-Macroglobulin synthesis was induced by dexamethasone concentrations of 10(-8) M or higher with a maximum at a concentration of 10(-7) M. alpha 1-Acid glycoprotein was synthesized in the absence of dexamethasone; however, its synthesis was also greatly stimulated by dexamethasone concentrations of 10(-8)-10(-6) M. Synthesis of alpha 1-proteinase inhibitor was stimulated only 1.4-fold at a dexamethasone concentration of 10(-7) M. The kinetics of induction of alpha 2-macroglobulin and alpha 1-acid glycoprotein were studied at a dexamethasone concentration of 10(-7) M. After an initial lag phase of 3 h the synthesis of both proteins showed a steady increase during 2 days. Synthesis of albumin remained unchanged under these experimental conditions. Unlike alpha 2-macroglobulin and alpha 1-acid glycoprotein tyrosine aminotransferase activity increased already during the first 3 h of induction by dexamethasone with a maximum at 12 h followed by a slight decrease.

Acute-Phase Proteins↗
PubMed1983

Serum concentrations of deoxycorticosterone in women during the luteal phase of the ovarian cycle are not suppressed by dexamethasone treatment.

We determined the serum levels of deoxycorticosterone (DOC) in plasma of six healthy, apparently ovulatory women during the mid-follicular and mid-luteal phases of their ovarian cycles; and we evaluated the effect of dexamethasone (1 mg by mouth) on the concentrations of DOC and cortisol in serum at times when plasma progesterone levels were high or low. The serum levels of DOC, unlike those of cortisol, did not vary significantly in single blood samples obtained in the morning (8-10 a.m.) and afternoon (3-5 p.m.); and serum DOC levels in women were significantly higher (P less than 0.05) during the mid-luteal phase than during the mid-follicular phase of the cycle. There were unmistakable diurnal variations in serum levels of cortisol, and cortisol concentrations were reduced to less than 20% of pretreatment levels after the ingestion of 1 mg dexamethasone during the mid-follicular or mid-luteal phase. The serum concentrations of DOC were reduced only to approx 70% of pretreatment levels after dexamethasone ingestion during the follicular phase. The serum levels of DOC did not decline significantly after administration of dexamethasone during the mid-luteal phase, when progesterone levels in serum are high (14-16 ng/ml). Blood samples also were obtained at hourly intervals during the 24 h before and after dexamethasone administration in one woman during the follicular phase and in another woman the during the early luteal phase (progesterone levels = 1-3 ng/ml) of the ovarian cycle. DOC levels (pre-dexamethasone) fluctuated in synchrony with those of cortisol in the woman studied during the follicular phase but not in the woman studied during the early luteal phase of the cycle. In the post-dexamethasone period, plasma cortisol levels were suppressed for at least 24 h in both women whereas DOC levels were decreased only partially. We conclude that plasma DOC is derived from both adrenal secretion and from extraadrenal 21-hydroxylation of progesterone--the latter source of DOC is not affected by dexamethasone suppression of ACTH secretion.

Desoxycorticosterone↗
PubMed1987

Chronic noise stress and dexamethasone administration on blood pressure elevation in the rat.

In order to evaluate the role of ACTH and corticosterone in the elevated blood pressure produced by chronic noise, we have studied the effect of dexamethasone administration on blood pressure. Adrenal response was measured by alterations in plasma corticosterone levels in two experimental groups (Dexamethasone treated rats, Dexamethasone-noise stressed rats) and compared with a Control and a Noise-stressed group. Chronic noise stress with a frequency of 2640 Hz, power of 30 w and duration of 15 min daily was used for 30 consecutive days. Dexamethasone was administered by subcutaneous injection of 100 micrograms/100 g b.wt daily. Blood pressure was measured by an indirect tail cuff method and corticosterone levels by specific RIA. Dexamethasone administration decreases corticosterone levels but increases blood pressure. Dexamethasone-treated noise stressed rats show higher residual corticosterone levels and a more marked increase on blood pressure than rats treated with dexamethasone alone. Thus noise-stress and dexamethasone administration have opposing effects on corticosterone release and a synergistic effect on blood pressure elevation.

Animals↗
PubMed1995

Simultaneous evaluation of dexamethasone-induced apoptosis and micronuclei in rat primary spleen cell cultures.

Apoptosis or programmed cell death is a biological event that is biochemically and morphologically distinct from cellular necrosis. Nonetheless, its relationship has not been studied in terms of a cytogenetic endpoint such as micronucleus formation. In the present study, based on cytological observations, the incidence of dexamethasone-induced apoptotic cells was related to the frequency of micronucleated cells in vitro. Rat primary spleen cells were grown in 6-well plates with RPMI 1640 media using concanavalin A and lipopolysaccharide as mitogens. At culture initiation, the test agent dexamethasone (10, 20 or 40 microM) and a cytokinesis inhibitor cytochalasin B (3 micrograms/ml) were added. Cultures were harvested 18 h and 40 h later. Slides were prepared and stained with Diff-Quik stain. Frequencies of apoptotic cells and micronucleated binucleate cells were enumerated cytologically based on 500 cells per treatment from the same slides. The results showed a dose-dependent increase in the number of apoptotic cells in rat spleen cultures treated with dexamethasone. At 18 h, the percentages of apoptotic cells were 0.8, 1.6, 3.4 and 4.4 with 0, 10, 20 and 40 microM dexamethasone, respectively. The corresponding percentages of apoptotic cells at 40 h were: 2.8, 2.6, 5.6 and 10.4. However, at the same concentrations of dexamethasone, the micronucleus frequency in binucleate cells remained relatively unchanged. The phenomenon of apoptosis induced by dexamethasone was confirmed biochemically based on a characteristic DNA 'ladder' pattern by gel electrophoresis. These data suggest that dexamethasone at the concentrations which induced apoptosis did not produce cytogenetic damage. Also, these findings indicate that micronucleus formation and nuclear changes leading to apoptosis are separate events and these endpoints may not be closely correlated for dexamethasone.

Animals↗