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PubMed1997

Regulation of expression of the [3H]-dofetilide binding site associated with the delayed rectifier K+ channel by dexamethasone in neonatal mouse ventricle.

Developmental shortening of cardiac action potential duration in mouse appears to result, at least in part, from replacement of the rapid component of the delayed rectifying potassium current (IKr) with the transient outward current (ItO1). This developmental decrease in the IKr current density was paralleled by a loss of the high affinity [3H]-dofetilide binding site and loss of prolongation of action potential duration by dofetilide. Since glucocorticoid treatment prevented the developmental shortening of action potential duration in rats in the perinatal period, we hypothesized that chronic dexamethasone treatment would alter the developmental loss of IKr channel expression in mice. Accordingly, 10-day-old mice were randomly allocated to chronic in vivo dexamethasone treatment (1 mg/kg) or placebo treatment for 3-5 days. At 15 days of life, transmembrane action potentials were recorded in right ventricular endocardium and [3H]-dofetilide equilibrium binding studies were performed. The baseline action potential duration in the dexamethasone-treated animals was significantly greater than that in the control group (66+/-3 v 54+/-10 ms, respectively; P<0.01). Moreover, dofetilide significantly prolonged action potential duration in the dexamethasone-treated animals, but had no effect on the placebo-treated group (P<0.01). In addition, a high affinity [3H]-dofetilide binding site (Kd 96+/-21 nM and Bmax 69+/-13 fmoles/mg protein) was observed in the dexamethasone-treated group (n=5), whereas no specific [3H]-dofetilide binding was observed in the placebo-treated group. In conclusion, dexamethasone modulates developmental regulation of IKr channel expression in mouse ventricle.

Action Potentials↗
PubMed2005

Should dexamethasone be part of routine therapy of bacterial meningitis in industrialised countries?

Two issues are clear from the data available regarding the current place of dexamethasone in routine management of suspected bacterial meningitis in industrialised countries. First, there is now good evidence of benefit from adjunctive dexamethasone therapy which is not confined to Hib meningitis, but in the case of pneumococcal meningitis probably requires that dexamethasone is given with or before, rather than after, parenteral antibiotics. In meningococcal meningitis, statistically significant benefit has not been demonstrated for any outcome, even in meta-analyses, but the point estimate is in the direction of benefit and failure to demonstrate an effect is more likely to be due to limited power from low event rates rather than no benefit; certainly there is no evidence of a detrimental effect. Most culture-negative cases of presumptive bacterial meningitis outside the neonatal period are likely to be due to one of the above 3 organisms. In the neonatal period or in some settings in developing countries, the spectrum of organisms is very different and extrapolation of these findings cannot be assumed. Second, the suggestion that dexamethasone is not applicable to certain subgroups in industrialised countries (such as cases not treated with cefuroxime, or some other sub-optimal therapy, or cases treated with vancomycin) (5) or that benefit only applies to hearing loss or Hib cases, either do not stand up to scrutiny or are not answerable from available data. What does this mean for clinical practice? The results of randomised controlled trials may not readily translate to clinical practice, particularly with respect to early commencement of steroids. The Sydney data show that in a representative developed country population with good access to services, after controlling for other prognostic variables, early corticosteroid therapy is associated with improved outcome. These data also show that deferred lumbar puncture is frequent and so criteria requiring presumptive identification of an organism are not practical to guide dexamethasone use, indeed those patients in whom lumbar puncture is deferred are more likely to have severe disease. This experience is an important addition to the findings from clinical trials of dexamethasone in pneumococcal meningitis in industrialised countries (5,6) as it demonstrates that adjunctive steroid therapy is beneficial in a 'real world' situation. In addition, the prospect of clinical trials in children, already limited by small case numbers, will be further reduced when the use of the conjugate pneumococcal vaccines is widespread. In Canada, a trend to decreasing use of corticosteroids was noted between 1991 and 1999, probably reflecting conflicting evidence. (16). Unless clear protocols are in place, the commencement of steroids before or with antibiotics will be difficult to implement in emergency situations, as illustrated by the data from Sydney.

Anti-Inflammatory Agents↗
PubMed1990

Dose- and time-dependent effects of dexamethasone on rat brain following cold-injury oedema.

Experiments were carried out with a rat model of brain-injury oedema to establish the most efficacious dose and administration schedule for dexamethasone treatment. The results indicate that there are statistically significant dose- and time-dependent effects for dexamethasone treatment of cold-injury oedema. The equivalent of a 500 mg dose of dexamethasone had the highest anti-oedematous effect. With higher doses no further improvement could be achieved and the potential of hazardous effects increased. As expected, pretraumatic drug treatment had the greatest therapeutic effect. Dexamethasone administration up to about 30 min after cold injury led to measurable beneficial results. Drug injection from 90 min or longer after injury only slightly reduced cerebral oedema. No therapeutic effects were found when dexamethasone was administered more than 21 hours after inducing cerebral oedema. If similar results are obtained in corresponding clinical studies, the recommended dexamethasone dose and schedule for treating traumatic cerebral oedema would be: 1) high doses of drug (e.g. 500 mg); 2) drug administration to begin as early as possible, preferably within the first 2-3 hours after head injury; and 3) treatment should be terminated within 2-3 days to avoid major side effects.

Animals↗
PubMed1991

Twice-daily tapering dexamethasone treatment during cranial radiation for newly diagnosed brain metastases.

Twenty evaluable patients with newly diagnosed brain metastases underwent treatment with a novel dose/schedule of dexamethasone aimed at reducing steroid toxicity during palliative radiation therapy. All patients received twice daily dexamethasone starting at 8 mg bid for four days then 4 mg bid for four days then 2 mg bid until the last day of radiation therapy. The radiation prescriptions were not standardized varying from 2000 cGy/5 fractions to 5800 cGy/29 fractions. Fourteen patients received dexamethasone for a minimum of 24 hours before their first radiation treatment and 7 (50%) experienced improvement in neurologic symptoms/signs prior to starting radiation treatments. Fourteen patients completed the planned course of radiation and dexamethasone. Only 1 patient needed to restart dexamethasone within 30 days of finishing radiation because of steroid reversible neurologic deficits. Steroid toxicity was mild including hyperglycemia (1), candida esophagitis (1), steroid pseudorheumatism (2), peripheral edema (1) and steroid withdrawal syndrome (1). Only two toxic events were recorded in patients receiving steroids less than 21 days. Twice daily dexamethasone appears to provide good clinical results with minimal morbidity.

Administration, Oral↗
PubMed1996

Chronic dexamethasone administration decreases noradrenaline-stimulated, but not serotonin-stimulated, phosphoinositide metabolism in the rat brain.

The present study was undertaken to investigate the effects of chronic administration of dexamethasone on the noradrenaline- and serotonin-stimulated (5-HT-stimulated) phosphoinositide metabolism in hippocampus and frontal cortex of the rat brain. For determination of phosphoinositide metabolism, slices from selected regions of the rat brain (hippocampus or frontal cortex) were loaded with myo- [3H] inositol and stimulated with the agonists (noradrenaline or 5-HT) in the presence of LiCl (7.5 mM). Administration of dexamethasone (1 mg/kg/day) every 2nd day for 14 days markedly reduced the noradrenaline-stimulated phosphoinositide metabolism in the rat hippocampus (IP1: 60% of the control value). In the rat frontal cortex, the noradrenaline-stimulated phosphoinositide metabolism was less depressed by the chronic administration of dexamethasone (IP1: 84% of the control value). However, the chronic administration of dexamethasone did not affect the 5-HT-stimulated phosphoinositide metabolism in the rat brain. The binding characteristics of alpha 1 -adrenoceptors and 5-HT2A receptors were unaffected by the chronic treatment with dexamethasone. These results indicate that chronic administration of dexamethasone induces regional and neurotransmitter-specific changes of phosphoinositide metabolism in rat brain. The results suggest that the reduction of noradrenaline-stimulated phosphoinositide metabolism is due to modification of the intracellular signal transduction system.

Animals↗
PubMed1991

Evaluation of a single intravitreal injection of dexamethasone phosphate in vitrectomy surgery for diabetic retinopathy complications.

For evaluation of the efficacy and toxicity of dexamethasone phosphate after pars plana vitrectomy, 27 randomly selected eyes received 0.8 mg intravitreal dexamethasone phosphate and 30 control eyes did not receive this injection. No signs of dexamethasone phosphate toxicity were observed during 6 months of follow-up evaluations. Visual acuities of 20/40 or better were obtained in 26% of the dexamethasone-treated group and 33% of the control group, and those of 20/200 or better were obtained in 74% of the dexamethasone-treated eyes and 73% of the control eyes. Moderate anterior chamber flare or fibrin formation occurred in only 15% of the dexamethasone-treated eyes but in 27% of the control eyes one day after surgery. Lens changes occurred equally in both groups. None of the eyes in either group developed substantial intraocular proliferation or membranes following surgery.

Adult↗
PubMed1993

Dexamethasone increases airway epithelial cell neutral endopeptidase by enhancing transcription and new protein synthesis.

Neutral endopeptidase (NEP; also known as EC 3.4.24.11, CALLA) is a widely distributed membrane-bound enzyme that hydrolyzes many biologically important endogenous peptides. To evaluate the influence of glucocorticoids on airway epithelial cell NEP expression, we used the human airway epithelial cell line Calu-1. Cells, grown to confluency in Dulbecco's modified Eagle medium with 10% fetal bovine serum and penicillin-streptomycin, were incubated with different concentrations of dexamethasone or vehicle alone in the presence or absence of actinomycin D or cycloheximide for planned times. NEP activity was assayed at the end of treatment employing reverse-phase, high-pressure liquid chromatography. In some experiments, changes in NEP-specific mRNAs in the presence or absence of dexamethasone and/or the inhibitors were also evaluated by Northern blot analysis. We found that dexamethasone increased Calu-1 NEP activity in a dose- and time-dependent manner. Northern blot analysis indicated that NEP-specific mRNAs were also increased by dexamethasone. Furthermore, neither actinomycin D nor cycloheximide inhibited the increases in NEP activity and NEP-specific mRNAs caused by dexamethasone stimulation. We speculate, therefore, that dexamethasone increases NEP expression of these airway epithelial cells by enhancing transcription and new protein synthesis.

Carcinoma, Squamous Cell↗
PubMed1993

Dexamethasone induces chondrogenesis in organoid culture of cell mixtures from mouse embryos.

The effect of dexamethasone on morphogenesis and differentiation of cells obtained from mouse embryos grown at high density in vitro was investigated. Cells from decapitated mouse embryos of day 10 to day 13 were isolated by enzymatic treatment and grown at high density at the medium/air interface in organoid culture. After 28 days in culture, organoid-like structures such as vesicles, gland-like structures and cell aggregates had developed, dependent on the stage of the embryos. After the addition of 10(-7) M dexamethasone, cartilage had formed in cultures of cells from day-10, -11 and -12 embryos. It was maximal in cultures of day-11 cells and rare in day-10 cells. No cartilage was found in cultures of day-13 cells. Cartilage induction was similar in cultures treated with 10(-6) and 10(-7) M dexamethasone, but clearly less in cultures treated with 10(-8) M. Only minute amounts of cartilage were detectable after dexamethasone treatment of cells obtained from decapitated embryos (day-11 and -12) whose limb buds had been cut off. In organoid cultures of pure limb bud cells, 10(-7) M dexamethasone had no influence on chondrogenesis. The results indicate that the cells inducible to form cartilage by dexamethasone originate from the limb buds. Glucocorticoid induction of chondrogenesis has not been described in vivo. The dependency of both chondrogenesis and expression of glucocorticoid receptor on cell density in vitro may be the cause for this effect.

Animals↗
PubMed1981

Effects of prednisolone and dexamethasone in vivo and in vitro: studies of insulin binding, deoxyglucose uptake and glucose oxidation in rat adipocytes.

We have studied the effects of dexamethasone and prednisolone in vitro and in vivo on insulin binding, deoxyglucose uptake and glucose oxidation in rat adipocytes. In the studies in vivo, rats were treated for 22 h with dexamethasone (30 micrograms/kg) or prednisolone (200 micrograms/kg). Following sacrifice, adipocytes were prepared and the results demonstrated that cells from prednisolone treated rats showed a 17% increase in insulin binding and increased rates of basal and insulin stimulated deoxyglucose uptake and glucose oxidation. Conversely, dexamethasone administration resulted in a 22% decrease in insulin binding, and decreased rates of deoxyglucose uptake and glucose oxidation by the cells. Thus, prednisolone and dexamethasone had opposite effects in vivo. In contrast to the opposite effects of the two glucocorticoids in vivo, dexamethasone and prednisolone (each at a concentration of 1 mumol/l) had similar effects on adipocytes in vitro. Incubation of adipocytes with the steroids did not alter insulin binding, while both agents led to a comparable decrease in the rates of basal and insulin stimulated deoxyglucose uptake and glucose oxidation. Thus, dexamethasone and prednisolone have opposite effects on adipocyte glucose metabolism in vivo but have similar effects in vitro.

Adipose Tissue↗
PubMed1995

Effect of dexamethasone on sodium channel block and densities in A6 cells.

The association (ON) and dissociation (OFF) rates of either positively charged amiloride or its uncharged analogue, CDPC (6-chloro-3, 5-diaminopyrazine-2-carboxamide), with the apical Na+ channel protein of renal A6 cells were analysed during exposure to the synthetic glucocorticoid, dexamethasone, using noise analysis. These rates were further used to reach specific conclusions about single-channel current, channel density and open probability of the channel in the absence of the blocker. Short-term exposure (3 h) to 10(-7) mol/l dexamethasone at the basolateral side increased the short-circuit current, Isc by 85%, without a change in the ON and OFF rates of the interaction between amiloride and the Na+ channel. A longer incubation (24 h) with dexamethasone tripled the current with a notable increase in the ON rate of the interaction between amiloride and the and channel. The OFF rate remained constant. The effects of dexamethasone on the rate constants of the reaction of amiloride with the channel did not match with the expected changes in membrane potential. On the other hand, ON and OFF rates of the interaction between neutral CDPC and the channel were not influenced by a 24-h incubation with dexamethasone. Further calculations disclosed that the gain in macroscopic current after a 24-h incubation with dexamethasone might be explained by an increase in Na+ channel density, and, to a lesser extent, by a rise in single-channel current. This all occurred without a change in the fraction of time spent by the channel in the conducting state in the absence of the blocker.

Amiloride↗
PubMed1989

Comparison of the effects of dexamethasone and 13-cis-retinoic acid on connective tissue biosynthesis in human skin fibroblasts.

The effects of glucocorticoids and retinoids on connective tissue biosynthesis were studied in cultured human skin fibroblasts (HSFs). More specifically attention was paid to the effects of dexamethasone and 13-cis-retinoic acid (RA) on total protein and collagen synthesis and on collagen and fibronectin mRNA levels. The results indicated that dexamethasone reduced the relative collagen synthesis and collagen mRNA levels in HSFs and increased the total incorporation of proline into proteins, the latter effect being due to increased activity in the intracellular proline pool. 13-cis-RA did not affect collagen synthesis at the concentration studied (10(-7) M) but it did reduce the corresponding mRNA levels. Simultaneous addition of both dexamethasone and 13-cis-RA or etretinate resulted in the largest decrease in type I and type III procollagen mRNA levels, indicating that retinoids do not oppose the effect of glucocorticoids on collagen synthesis in cultured HSFs. For comparison the effects of dexamethasone and 13-cis-RA on the mRNA levels of another extracellular matrix component, fibronectin, and of a constitutive enzyme, glyceraldehyde-3-phosphate dehydrogenase, were also studied. The results indicated, that dexamethasone treatment did not alter fibronectin mRNA levels in HSFs, while 13-cis-RA did so to a marked extent. Both dexamethasone and 13-cis-RA also reduced the mRNA level of glyceraldehyde-3-phosphate dehydrogenase, indicating that glucocorticoids and retinoids have both similar and different effects on gene expression in HSF.

Cell Line↗
PubMed1979

The response of focal ischemic cerebral edema to dexamethasone.

Twenty-four h after permanent occlusion of the middle cerebral artery (MCA) in the cat, the hemispheric swelling due to edema is markedly reduced under treatment with large doses of dexamethasone than is the case with the untreated group. The increase of regional water and sodium content in the MCA territory is less in the dexamethasone treated group, whereas the potassium changes in the ischemic tissue showed only small differences between the two groups. The potassium content of the non-ischemic tissue is slightly increased in the dexamethasone treated animals when comparing with the untreated group. RISA activity in the tissue is increased in the grey and the white matter of both groups. The less marked RISA-131 activity in the cortical grey matter of the treated animals indicates blood-brain barrier damage of a smaller degree due to dexamethasone. These findings indicate a beneficial effect of dexamethasone on local ischemic edema. Regarding our results and the pharmacokinetics of this steroid the dexamethasone loading of a patient has to be in the range of about 100 mg per day for the adult, and has to be started immediately after the onset of a stroke.

Animals↗
PubMed1995

Protein synthesis-dependent induction of interleukin-1 beta by lipopolysaccharide is inhibited by dexamethasone via mRNA destabilization in human astroglial cells.

Dexamethasone inhibits lipopolysaccharide-induced synthesis of the cytokine, interleukin-1 beta, in cerebrospinal fluid of patients with bacterial meningitis. Along with monocytes, astrocytes are capable of producing lipopolysaccharide-induced interleukin-1 beta in the central nervous system. The objective of this study was to investigate the induction of interleukin-1 beta mRNA by lipopolysaccharide, and the inhibition of this process by dexamethasone, in human astrocytes using the astrocytoma cell line U-373MG as a model system. Dexamethasone-mediated inhibition of induction of interleukin-1 beta mRNA by lipopolysaccharide required a functional glucocorticoid receptor. In contrast to monocytes, lipopolysaccharide induction of interleukin-1 beta mRNA in U-373MG cells required de novo protein synthesis. Dexamethasone also had no effect on lipopolysaccharide-induced interleukin-1 beta transcriptional initiation in U-373MG cells. U-373MG cells were similar to monocytes, however, with respect to the ability of dexamethasone to decrease interleukin-1 beta mRNA half-life. These findings demonstrate that the mode of lipopolysaccharide induction of interleukin-1 beta mRNA, and inhibition of this process by dexamethasone, can vary in different cell types.

Astrocytes↗
PubMed1996

Single high-dose dexamethasone improves the effect of ondansetron on acute chemotherapy-induced nausea and vomiting but impairs the control of delayed symptoms.

The introduction of serotonin receptor (5-HT3) antagonists has improved the control of acute nausea and vomiting induced by cancer chemotherapy, but they seem to have little or no effect on delayed symptoms. Corticosteroids are known to reduce both acute and delayed nausea and vomiting. The aim of the present study was to test the hypothesis that a single high dose of dexamethasone (20 mg), a long-acting corticosteroid, given after cisplatin and in addition to ondansetron (8 mg three times a day), would enhance the control of both acute and delayed nausea and vomiting. A group of 104 chemotherapy-naive ovarian cancer patients, scheduled for at least three cycles of combination chemotherapy including cisplatin (50 mg/m2), were randomly allocated to receive either dexamethasone or placebo in addition to ondansetron. Two-thirds of the patients received doxorubin and melphalan on the day before cisplatin and 1/3 received doxorubicin immediately before cisplatin. Unexpectedly we found, in all three chemotherapy cycles, that patients receiving dexamethasone suffered from more delayed nausea and vomiting than patients receiving placebo. In patients with no acute nausea or vomiting, the boomerang effect of dexamethasone could be seen on the first day after chemotherapy. In a follow-up study on 5 patients not included in the randomized trial, dexamethasone induced a pronounced reduction in urinary cortisol excretion on the day after chemotherapy with a return to normal excretion on day 2. It is concluded that a single high dose of dexamethasone does not seem appropriate for controlling delayed nausea and vomiting.

Antiemetics↗
PubMed1991

The effect of in vitro and in vivo dexamethasone on human neutrophil function.

There is a significant fall in PMN chemotaxis to the peptide FMLP in response to increasing concentrations of dexamethasone in vitro. The response fell in a dose related manner from a control value of 53.7 SE +/- 9.6 cells per high power field (cpf) to 47.3 SE +/- 8.1 at 10(-6) M (p less than 0.05) and 24.7 +/- 8.9 at 10(-3) M (p less than 0.025). A similar response was observed for the chemoattractants zymosan activated serum and the sol phase of purulent sputum. The effect was independent of protein synthesis or the period of incubation. Twelve milligrams of dexamethasone taken daily by 6 healthy volunteers resulted in a significant (p less than 0.025) reduction in the chemotactic response of PMN to 10(-8) M FMLP (from 29.5 +/- 1.55 to 13.7 +/- 1.8 cpf) which was apparent within 2 hours of taking the first dose. This effect was sustained for the three days on which dexamethasone was taken but returned to normal 7 days after the last dose had been administered. Dexamethasone therapy had no effect on unstimulated PMN superoxide anion production either in vitro or in vivo. The in vivo effect on neutrophil function occurred at mean serum dexamethasone concentrations of 1.26 (+/- 0.28) X 10(-7) M on day 1, 1.44 (+/- 0.15) X 10(-7) M on day 2 and 1.31 (+/- 0.13) X 10(-7) M on day 3. Thus we conclude that dexamethasone concentration which inhibit PMN chemotaxis in vivo are much lower than those required to exert the same effect in vitro.

Chemotaxis, Leukocyte↗
PubMed1988

Dexamethasone effects on vascular volume and tissue hematocrit in experimental RG-2 gliomas and adjacent brain.

We have studied the effects of dexamethasone, a corticosteroid commonly used to treat brain tumors, on vascular volume and tissue hematocrit in RG-2 experimental rat gliomas. 125I-RISA (radioiodinated serum albumin) was used to measure tissue plasma vascular volume (Vp) and 51Cr labeled red cells were used to measure tissue red cell volume (Vrbc). Quantitative autoradiography was used to obtain local measurements of Vp and Vrbc in different brain and tumor regions. From these experimentally measured values, we calculated the tissue vascular volume (Vv), tissue hematocrit (THct) and systemic arterial hematocrit (AHct). The value reported primarily reflect capillary and small vessel volumes since blood drained from larger vessels during tissue processing and large vascular structures were avoided during analysis of the autoradiographic images. A total of 110 tumors were studied in 29 animals. There was a consistent trend for Vp and Vv to be reduced in all tumor regions after dexamethasone treatment, although a significant decrease was seen only in tumor center. Dexamethasone did not affect Vp or Vv in tumor-free brain regions. Dexamethasone appeared to have little effect on Vrbc in any brain or tumor region. THct was consistently, although not significantly, higher in tumors after treatment with dexamethasone; THct in tumor-free brain regions was unaffected by dexamethasone treatment.

Animals↗
PubMed1987

The pharmacokinetics of single high doses of dexamethasone in cancer patients.

We have given single high doses of dexamethasone phosphate by intravenous infusion as an antiemetic to 15 cancer patients receiving regimens containing cisplatin and/or doxorubicin. The patients received graded doses of dexamethasone phosphate, in the range 40-200 mg, dependent upon nausea and vomiting scores, during up to three consecutive cycles of cancer chemotherapy. Plasma and urine concentrations of dexamethasone (dexamethasone alcohol) were measured by HPLC. The plasma concentration - time data were described by an open two-compartment model. The pharmacokinetic variables were independent of the dose of dexamethasone over the range studied. The terminal half-time was 4.0 +/- 0.4 h and the total body clearance was 3.5 +/- 0.4 ml X min-1 X kg-1. The volume of the central compartment and the total apparent volume of distribution were 0.23 +/- 0.03 and 1.0 +/- 0.1 l X kg-1 respectively. Approximately 8% of the dose was excreted into the urine as dexamethasone.

Aged↗
PubMed1999

Consequences of treatment with dexamethasone in rats on the susceptibility of total plasma and isolated lipoprotein fractions to copper oxidation.

According to the oxidative hypothesis of atherosclerosis, a hyperoxidizability of lipoproteins could favor the development of the atherosclerotic process. Besides, it has been recently reported that models of elevated very-low-density-lipoprotein (VLDL) levels in rats resulted in an increased susceptibility of these VLDL to oxidation. Treatment with dexamethasone classically induces an increase in plasma VLDL concentration. The aim of our study was thus to assess the effects of a treatment with dexamethasone in rats on the susceptibility to copper oxidation, both on total plasma and on isolated lipoproteins. Male Sprague-Dawley rats aged three months were treated with a daily intraperitoneal injection of dexamethasone (1.5 mg per kg) for five days (DEX group), whereas control rats were fed ad libitum (AL group). In order to take into account the decrease of food intake induced by dexamethasone treatment, a group of pair-fed rats was constituted (PF group). These rats had the same food intake as rats of the DEX group and were treated with a daily isovolumic intraperitoneal injection of NaCl for 5 d. After 5 d treatment, rats were fasted overnight, then killed, and blood was collected on EDTA. Low-density lipoproteins (VLDL + LDL) and high-density lipoproteins (HDL) were isolated by ultracentrifugation. A copper oxidation was conducted both on total plasma and on isolated lipoproteins. As expected, after treatment with dexamethasone, plasma exhibited increased triglyceride and glucose levels. Similarly, VLDL + LDL of rats from the DEX group were enriched with triglycerides, when compared with VLDL + LDL of the other two groups of rats. Our major finding was a marked increase in the susceptibility of total plasma of the DEX group to copper oxidation, in comparison with the other two groups of rats. This oxidizability was assessed by the maximal level of oxidation products absorbing at 234 nm and classically considered to be conjugated dienes (7.46+/-0.70 micromol L(-1) in the DEX group vs. 3.36+/-0.40 and 2.05+/-0.60 micromol L(-1) in the AL and PF groups, respectively). Nevertheless, this higher oxidizability was not observed in the isolated lipoprotein fractions, as shown by the formation of lipid peroxidation products such as conjugated dienes, thiobarbituric-acid reactive substances, hydroperoxides, 7-ketocholesterol, and dienals. This is not in agreement with other models of hypertriglyceridemia that have been reported to induce a hyperoxidizability of lipoproteins in rats. Our results led us to hypothesize that other plasma components such as proteins could be involved in this susceptibility to oxidation. Indeed, the severe protein catabolism induced by dexamethasone treatment could support this hypothesis, by forming protein components that are more susceptible to oxidation, as shown by an increased carbonyl formation upon plasma copper oxidation.

Animals↗