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The effects of dexamethasone on the response of bronchus-associated lymphoid tissue to intranasal administration of formalin-killed Pasteurella haemolytica A2 in goats

Zamri-Saad M, Effendy AW

Vet Res Commun, 1999 Dec;23(8):467-73.
PMID: 10672963

A trial was conducted to observe the immediate and chronic effects in goats of dexamethasone administration on the bronchus-associated lymphoid tissue (BALT) response to intranasal administration of formalin-killed Pasteurella haemolytica A2. Twenty-four goats were divided into four groups. Those in group 1 were injected intramuscularly with 1 mg/kg dexamethasone on three consecutive days, followed by intranasal exposure to formalin-killed P. haemolytica A2 one day after the last dexamethasone treatment. The goats in group 2 were similarly injected with dexamethasone followed by intranasal exposure to formalin-killed P. haemolytica A2 21 days after the last dexamethasone treatment. The animals in group 3 were exposed intranasally to formalin-killed P. haemolytica A2 without prior dexamethasone treatment. The animals in group 4 were untreated controls. The intranasal exposures to formalin-killed P. haemolytica A2 were repeated 2 weeks later. Intranasal exposure to formalin-killed P. haemolytica 1 day after dexamethasone treatment further reduced the number and size of BALT compared to the untreated control. Significantly (p < 0.01) more reduction of BALT occurred in goats exposed to formalin-killed P. haemolytica A2 21 days after dexamethasone treatment. On the other hand, intranasal exposure of goats without prior dexamethasone treatment stimulated the BALT compared to the untreated controls.

Matched MeSH terms: Dexamethasone/pharmacology*
Mesenchymal stem cells facilitate cardiac differentiation in Sox2-expressing cardiac C-kit cells in coculture

Leong YY, Ng WH, Umar Fuaad MZ, Ng CT, Ramasamy R, Lim V, et al.

J Cell Biochem, 2019 06;120(6):9104-9116.
PMID: 30548289 DOI: 10.1002/jcb.28186

Stem cell therapy offers hope to reconstitute injured myocardium and salvage heart from failing. A recent approach using combinations of derived Cardiac-derived c-kit expressing cells (CCs) and mesenchymal stem cells (MSCs) in transplantation improved infarcted hearts with a greater functional outcome, but the effects of MSCs on CCs remain to be elucidated. We used a novel two-step protocol to clonogenically amplify colony forming c-kit expressing cells from 4- to 6-week-old C57BL/6N mice. This method yielded highly proliferative and clonogenic CCs with an average population doubling time of 17.2 ± 0.2, of which 80% were at the G1 phase. We identified two distinctly different CC populations based on its Sox2 expression, which was found to inversely related to their nkx2.5 and gata4 expression. To study CCs after MSC coculture, we developed micron-sized particles of iron oxide-based magnetic reisolation method to separate CCs from MSCs for subsequent analysis. Through validation using the sex and species mismatch CC-MSC coculture method, we confirmed that the purity of the reisolated cells was greater than 85%. In coculture experiment, we found that MSCs prominently enhanced Ctni and Mef2c expressions in Sox2 pos CCs after the induction of cardiac differentiation, and the level was higher than that of conditioned medium Sox2 pos CCs. However, these effects were not found in Sox2 neg CCs. Immunofluorescence labeling confirmed the presence of cardiac-like cells within Sox2 pos CCs after differentiation, identified by its cardiac troponin I and α-sarcomeric actinin expressions. In conclusion, this study shows that MSCs enhance CC differentiation toward cardiac myocytes. This enhancement is dependent on CC stemness state, which is determined by Sox2 expression.

Matched MeSH terms: Dexamethasone/pharmacology
Histomorphometric changes in the perirenal adipocytes of adrenalectomized rats treated with dexamethasone

Ahmad F, Soelaiman IN, Ramli ES, Hooi TM, Suhaimi FH

Clinics (Sao Paulo), 2011;66(5):849-53.
PMID: 21789391

INTRODUCTION: Prolonged steroid treatment administered to any patient can cause visceral obesity, which is associated with metabolic disease and Cushing's syndrome. Glucocorticoids have a profound negative effect on adipose tissue mass, giving rise to obesity, which in turn is regulated by the 11β-hydroxysteroid dehydrogenase type 1 enzyme. Adrenalectomized rats treated with dexamethasone exhibited an increase in visceral fat deposition but not in body weight.
OBJECTIVES: The main aim of this study was to determine the effect of dexamethasone on the histomorphometric characteristics of perirenal adipocytes of adrenalectomized, dexamethasone-treated rats (ADR+Dexa) and the association of dexamethasone treatment with the expression and activity of 11 β-hydroxysteroid dehydrogenase type 1 (11 β-hydroxysteroid dehydrogenase type 1).
METHODS: A total of 20 male Sprague Dawley rats were divided into 3 groups: a baseline control group (n = 6), a sham-operated group (n = 7) and an adrenalectomized group (n=7). The adrenalectomized group was given intramuscular dexamethasone (ADR+Dexa) 2 weeks post adrenalectomy, and the rats from the sham-operated group were administered intramuscular vehicle (olive oil).
RESULTS: Treatment with 120 μg/kg intramuscular dexamethasone for 8 weeks resulted in a significant decrease in the diameter of the perirenal adipocytes (p<0.05) and a significant increase in the number of perirenal adipocytes (p<0.05). There was minimal weight gain but pronounced fat deposition in the dexamethasone-treated rats. These changes in the perirenal adipocytes were associated with high expression and dehydrogenase activity of 11β-hydroxysteroid dehydrogenase type 1.
CONCLUSIONS: In conclusion, dexamethasone increased the deposition of perirenal fat by hyperplasia, which causes increases in the expression and dehydrogenase activity of 11 β-hydroxysteroid dehydrogenase type 1 in adrenalectomized rats.

Matched MeSH terms: Dexamethasone/pharmacology*
Dexamethasone modulation of gestation length and parturition in rats

Chatterjee A, Singh R, Chatterjee R

Pharmacol Res, 1993 May-Jun;27(4):359-64.
PMID: 8367382

Dexamethasone blocks aromatase and phospholipase A2 enzyme activities that are essentially involved in the formation of oestrogens and prostaglandins, the key chemicals to initiate parturition. The present study was undertaken to determine whether dexamethasone, a potent glucocorticoid, could prolong gestation and/or delay parturition in rats. Dexamethasone at 0.5 mg/rat/day from Day 19 through Day 21 of pregnancy consistently prolonged gestation. Only 36% of the pregnant rats had labour with an extended parturition time. Foetal mortality rate was also high. The remaining 64% pregnant rats that did not deliver showed intrauterine foetal death and resorption. Concomitant injection of oestradiol cyclopentylpropionate or prostaglandin F2 alpha on Day 19 effectively reversed the deleterious effects of dexamethasone. 100% of the pregnant rats had successful labour at term. The parturition time and foetal mortality rate were not different from controls. The results, therefore, indicate that an excess glucocorticoid that initiates parturition in sheep conversely prolongs gestation and delays parturition in rats.

Matched MeSH terms: Dexamethasone/pharmacology*
Effects of steroid hormones pretreatment on isoprenaline-induced cyclic adenosine 3',5'-monophosphate in rat lung

Nabishah BM, Merican Z, Morat PB, Alias AK, Khalid BA

Gen. Pharmacol., 1990;21(6):935-8.
PMID: 2177714

1. Steroid hormones have been shown to regulate the concentration of adrenergic and muscarinic receptors in many tissues. 2. The cyclic adenosine 3',5'-monophosphate (cAMP) content in rat lung tissues in response to either dexamethasone, corticosterone, deoxycorticosterone or progesterone for 7 days were measured following intraperitoneal injection of isoprenaline just before sacrificed. 3. There was a significant increase in cAMP level (P less than 0.001) in dexamethasone and corticosterone-treated rats compared to controls that received isoprenaline alone. 4. Pretreatment with deoxycorticosterone and progesterone suppressed the increase in cAMP in response to isoprenaline. 5. The effect of glucocorticoids in causing bronchodilatation in asthmatic patients is partly due to the restoration of adenyl cyclase responsiveness to beta-agonist.

Matched MeSH terms: Dexamethasone/pharmacology
Dexamethasone provoked mitochondrial perturbations in thymus: Possible role of N-acetylglucosamine in restoration of mitochondrial function

Venugopalan SK, T S S, V N, S M M, S R

Biomed Pharmacother, 2016 Oct;83:1485-1492.
PMID: 27619103 DOI: 10.1016/j.biopha.2016.08.068

Thymus mitochondria play a crucial role in immune function. This study identifies the novel protective role of N-Acetylglucosamine (NAG) in dexamethasone (DEX) induced mitochondrial perturbations in mice thymus. Mice were induced with DEX (5mg/kg) and treated with NAG i.p. (266μg/kg, 400μg/kg and 800μg/kg) for 14 days, Withanolide A (800μg/kg) has been used as positive control. Dose dependent treatment of NAG against DEX significantly restored the mitochondrial enzyme levels (ICDH, KDH, SDH and MDH) and elevated the mitochondrial glutathione antioxidants defense (GSH, SOD, GPX and GST) thus improving the ATP status which was confirmed by ultrastructural alterations in mitochondria and nucleus using TEM studies. Further histopathological studies also revealed that NAG attenuate DEX induced thymotoxicity. Finally, the study concludes that dose dependent treatment of NAG supports a potential role in preventing DEX induced thymotoxicity and NAG acts as a beneficial pharmacological intervention in the DEX induced thymic repercussions.

Matched MeSH terms: Dexamethasone/pharmacology*
Effects of resveratrol on shedding and pathological dynamics in experimental B. melitensis infection in dexamethasone-treated nonpregnant Boer goats

Tanko PN, Mohd Yusoff S, Emikpe BO, Bejo SK, Salisi S

J Immunoassay Immunochem, 2019;40(4):419-438.
PMID: 31154897 DOI: 10.1080/15321819.2019.1620766

Brucellosis constitutes an infectious re-emerging zoonosis. Spread of diseases could be exacerbated by stress-induced immunosuppression. This study evaluated relationship between Brucella melitensis infection, shedding dynamics, dexamethasone-induced stress, pathological alterations and resveratrol ameliorative effects in goats. Twelve nonpregnant goats were divided into four groups A, B, C, and D of three animals each. Groups A and B were administered 107 CFU/mL of B. melitensis ocularly, 21 days prior to 7 days consecutive administration of dexamethasone (2 mg/kg). Group A was further administered resveratrol (5 mg/kg) intravenously for 5 consecutive days from day 31 post B. melitensis inoculation. Group C was administered similar dose of B. melitensis while group D was inoculated normal saline. Blood, nasal, ocular, and vaginal swabs were collected at intervals for analysis. The does were sacrificed at day 42 post inoculation (pi). Tissues were collected for tissue bacterial load determination, histopathology, and immunohistochemistry. Dexamethasone administration from day 21 pi increased the frequency in the shedding dynamics, tissue bacterial load, pathological alterations (frequency of microgranuloma and intensity of immunostaining) in group B while 5 days treatment with resveratrol following dexamethasone administration significantly reduced tissue bacterial load, decline in shedding dynamics, and ameliorate damage by dexamethasone administration/B. melitensis infection.

Matched MeSH terms: Dexamethasone/pharmacology*
Effects of steroid hormones on cyclic adenosine 3',5'-monophosphate levels in the rat lung

Nabishah BM, Khalid BA, Morat PB, Alias AK, Zainuddin M

J Endocrinol, 1992 Jul;134(1):73-6.
PMID: 1323640

The possible role of cyclic adenosine 3',5'-monophosphate (cAMP) in mediating the action of steroid hormones was investigated using the rat lung. Male rats were adrenalectomized and treated with olive oil, dexamethasone, corticosterone, deoxycorticosterone (DOC) or progesterone. At the end of 10 days, 100 micrograms isoprenaline/kg was injected intraperitoneally 5 min before the animals were killed to stimulate cAMP production. Adrenalectomy significantly decreased cAMP levels in the rat lung. Dexamethasone and corticosterone pretreatment reversed the effect of adrenalectomy whereas progesterone pretreatment but not DOC pretreatment significantly decreased lung cAMP levels. Cyclic AMP levels in normal female rats, whether pregnant or not, were not significantly different from those in male rats. We concluded that the absence of glucocorticoid, as after adrenalectomy, decreased the cAMP levels in rat lungs and that this could be reversed by either dexamethasone or corticosterone replacement. Progesterone reduced the cAMP content in rat lungs by acting as a glucocorticoid antagonist or by acting directly via progesterone receptors.

Matched MeSH terms: Dexamethasone/pharmacology
Caffeine neuroprotects against dexamethasone-induced anxiety-like behaviour in the Zebrafish (Danio rerio)

Khor YM, Soga T, Parhar IS

Gen Comp Endocrinol, 2013 Jan 15;181:310-5.
PMID: 23044054 DOI: 10.1016/j.ygcen.2012.09.021

The early-life stress has critical impact on brain development which can lead to long-term effects on brain functions during adulthood. It has been reported that caffeine possesses a protective effect in neurodegenerative diseases. Thus, this study investigates the potential of caffeine to protect brain functions from adverse effects due to stress exposure during early-life development in the male zebrafish. In the first part of this study, synthetic glucocorticoid, dexamethasone (DEX) (2-200 mg/L for 24 h) was used to induce stress effects in the zebrafish larvae from 4 to 5 days post-fertilisation (dpf) and the effect of DEX administration on zebrafish larvae on anxiety-like behaviour during adulthood in novel tank test was investigated. Next, the possible protective effect of caffeine pre-treatment (5-50 mg/L for 24 h from 3 to 4dpf) before DEX administration was studied. DEX-treated adult male zebrafish showed higher anxiety levels in behavioural tests, as seen in longer latency to enter the top part of the tank, lower transition numbers between the top and bottom parts with more time spent at the bottom and lesser time spent at the top and lower distance travelled at top part. The effect of DEX on anxiety-like behaviour was dose-dependent. Importantly, adult male zebrafish pre-treated with caffeine before DEX treatment did not show any anxiety-like behaviour. These results show that exposure to stress during early-life leads to anxiety-like behaviour in the adult male zebrafish but pre-treatment with caffeine protects from stress-induced anxiety.

Matched MeSH terms: Dexamethasone/pharmacology*
The effect of endogenous opioids on blood pressure during stress

Nordin M, Morat P, Zainora M

Clin Exp Pharmacol Physiol, 1987 Apr;14(4):303-8.
PMID: 3665195

1. A series of experiments were conducted to investigate the effect of endogenous opioids on blood pressure of laboratory rats during stress. 2. Rats subjected to 120 min immobilization showed a significant drop in systolic pressure which could be prevented by pretreatment injections of naloxone. 3. Adrenalectomized rats subjected to the same kind of stress showed a drop in systolic pressure equivalent to only 30% of the systolic pressure drop in the intact animals. This decrease in systolic pressure could also be prevented by pretreatment injections of naloxone. 4. It was concluded that the decrease in systolic pressure in intact rats during immobilization was mostly due to endogenous opioids released from the adrenal glands, whereas opioids of other origins such as the pituitary gland, were also important.

Matched MeSH terms: Dexamethasone/pharmacology
Mineralocorticoid and glycyrrhizic acid block stress induced hypotension in rats

Ruszymah BH, Nabishah BM, Aminuddin S, Khalid BA

Clin Exp Pharmacol Physiol, 1995 Jan;22(1):35-9.
PMID: 7768032

1. The aim of this study was to investigate the effect of repeated exposure to stress on tail blood pressure (TBP) of normal as well as GCA (glycyrrhizic acid) and steroid treated rats. Male Sprague-Dawley rats (250 g) were exposed to ether vapour to achieve light anaesthesia prior to TBP recording. Rats were injected with either normal saline or naloxone prior to exposure to stress. Tail blood pressure was recorded daily for 2 weeks. 2. We found that ether stress caused a transient drop in TBP in control as well as in dexamethasone (DEX) treated rats. The stress-induced fall in blood pressure was reduced by naloxone in control rats but not in DEX treated rats. However the transient drop in TBP following stress was not seen in either GCA or deoxycorticosterone (DOC) treated rats. 3. We conclude that first, the reduction in TBP was due to the release of endogenous opioids caused by stress. Second, DOC may block the release of such endogenous opioids, preventing the drop in TBP in response to stress, while DEX did not. Third, GCA caused a similar mineralocorticoid effect on reversing stress induced hypotension.

Matched MeSH terms: Dexamethasone/pharmacology*
Fulltext Investigating the in-vitro bioactivity, biodegradability and drug release behavior of the newly developed PES/HA/WS biocompatible nanocomposites as bone graft substitute

Salimi E, Asim MH, Abidin MNZ

Sci Rep, 2024 May 11;14(1):10798.
PMID: 38734777 DOI: 10.1038/s41598-024-61586-2

The nucleation of carbonate-containing apatite on the biomaterials surface is regarded as a significant stage in bone healing process. In this regard, composites contained hydroxyapatite (Ca10(PO4)6(OH)2, HA), wollastonite (CaSiO3, WS) and polyethersulfone (PES) were synthesized via a simple solvent casting technique. The in-vitro bioactivity of the prepared composite films with different weight ratios of HA and WS was studied by placing the samples in the simulated body fluid (SBF) for 21 days. The results indicated that the the surface of composites containing 2 wt% HA and 4 wt% WS was completely covered by a thick bone-like apatite layer, which was characterized by Grazing incidence X-ray diffraction, attenuated total reflectance-Fourier transform infrared spectrometer, field emission electron microscopy and energy dispersive X-ray analyzer (EDX). The degradation study of the samples showed that the concentration of inorganic particles could not influence the degradability of the polymeric matrix, where all samples expressed similar dexamethasone (DEX) release behavior. Moreover, the in-vitro cytotoxicity results indicated the significant cyto-compatibility of all specimens. Therefore, these findings revealed that the prepared composite films composed of PES, HA, WS and DEX could be regarded as promising bioactive candidates with low degradation rate for bone tissue engineering applications.

Matched MeSH terms: Dexamethasone/pharmacology

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