Corticosteroid-Induced Dermal Atrophy in The Rat

Young, J. M.; Yoxall, Bruce E; Wagner, Bonnie M.

doi:10.1111/1523-1747.ep12511301

Cited by 31 publications

(23 citation statements)

References 18 publications

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“…Anti-inflammatory activities of GCs differ in rats and humans, 44 and, since anti-inflammatory potencies and atrophogenic potential usually closely correlate in the classical GCs, the relative dermal atrophogenic potencies are also expected to vary between the species. 39 Compared to humans, the hairless rat seems to be more sensitive to atrophy following topical GC treatment. Anatomical differences of rodent and • High hurdles before testing is possible (e.g., toxicological characterization)…”

Section: 34mentioning

confidence: 99%

“…38 Overall the rat seems to be the best suited species. In the past, rats were shaved for atrophy assessment; 32,39 however, due to the unreliability of haired skin responses, 40,41 the use of hairless animals is the preferred now. Indeed, the current gold standard for pre-clinical testing of GR ligands is the hairless OFA hr/hr rat.…”

Section: Determining the Atrophogenic Potential In Pre-clinical In VImentioning

confidence: 99%

“…33,42 On the molecular level, various proteins like glucosaminoglycan, fibronectin and collagens may be used as indicators of GC effects. 39,43 Beside the direct parameters of skin atrophy, systemic effects of topically administered compounds can also be measured such as weight loss of body, thymus, spleen and adrenal glands. 34,35,39 The pros of in vivo pre-clinical tests compared to clinical tests are the reduced variability, higher cost-efficiency and in particular ethical aspects ( Table 1).…”

Section: 34mentioning

confidence: 99%

“…39,43 Beside the direct parameters of skin atrophy, systemic effects of topically administered compounds can also be measured such as weight loss of body, thymus, spleen and adrenal glands. 34,35,39 The pros of in vivo pre-clinical tests compared to clinical tests are the reduced variability, higher cost-efficiency and in particular ethical aspects ( Table 1). An evident con of many in vivo models is, however, their still limited predictivity for the human situation.…”

Section: 34mentioning

confidence: 99%

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Test systems for the determination of glucocorticoid receptor ligand induced skin atrophy

Schoepe

Schäcke

Asadullah

2011

Dermato-Endocrinology

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Section: 34mentioning

confidence: 99%

Section: Determining the Atrophogenic Potential In Pre-clinical In VImentioning

confidence: 99%

Section: 34mentioning

confidence: 99%

Section: 34mentioning

confidence: 99%

See 2 more Smart Citations

Test systems for the determination of glucocorticoid receptor ligand induced skin atrophy

Schoepe

Schäcke

Asadullah

2011

Dermato-Endocrinology

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“…In the skin of rats, prolonged treatment with glucocorticoids inhibited fibroblast growth and synthesis of cell products such as collagen and mucopolysaccharides (Young et al 1977).…”

Section: Introductionmentioning

confidence: 99%

Effect of Intravenously Infused Dexamethasone on Collagen Metabolism in Skin of Merino Sheep

Leish¹,

Panaretto²

1979

Aust. Jnl. Of Bio. Sci.

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The effects of an 8-day intravenous infusion of dexamethasone (7·6 mg kg-o . 75 body weight) on collagen biosynthes's and wool growth in skin were examined in four Merino wethers.Plasma dexamethasone concentrations reached their peaks during the first 24 h infusion, which were followed by relatively stable levels (c. 1 x 10-7 M) for the next 4-5 days. Minor increases in plasma dexamethasone levels were recorded during the final 2 days of treatment. Dexamethasone concentrations quickly fell below the level of detection once infusion ceased.Marked decreases in the wet weight, thickness and protein content of skin were observed at the end of infusion. DNA content was reduced to 42·4±4·9 % s.e.m. during the first 2 days of treatment, but in the next 4 days of infusion gradually increased to 85·0±12·5% of controls. The level of collagen (expressed as hydroxyproline content of its acid hydrolysate) was elevated throughout the infusion and then gradually declined in 3 weeks to about 60 % of controls.The biosynthesis of collagen measured by the rate of [14C]hydroxyproline formation and the activity of proline, 2-oxoglutarate dioxygenase (EC 1.14.11.2, formerly prolyl hydroxylase) was reduced during the first half of treatment to a greater extent than the rate of [14C]proline incorporation into proteins.Wool growth was reduced by 80·4 ± 11 ·6% in the post-infusion period which allowed three sheep out of four to be defleeced.Inhibition of collagen biosynthesis in sheep skin was due initially to a decrease in the activity of proline, 2-oxoglutarate dioxygenase and later to the reduced rate of proline incorporation into proteins. It ,was also evident that changes in biosynthetic rate of collagen were not reflected in the total level of skin collagen. The extent of wool growth depression in individual animals paralleled the changes in DNA content and the extent of collagen biosynthesis inhibition.

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Comparison of the antileukemic activity in vitro of dexamethasone and prednisolone in childhood acute lymphoblastic leukemia

Kaspers¹,

Veerman²,

Popp-Snijders³

et al. 1996

Med. Pediatr. Oncol.

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It is generally assumed that prednisolone (PRD) and dexamethasone (DXM) have equal glucocorticoid activity if PRD is given at sev enfold higher doses. Resuits of clinical studies of childhood acute lymphoblastic leukemia (ALL) suggested that DXM is more potent relative to PRD than assumed. The purpose of this study was to determine the relative antileukemic activ ity of PRD phosphate and DXM phosphate in 133 untreated childhood ALL samples in vitro, using the 3-(4,5-dimethylthiazol-2~y!)-2,5~diphenyltetrazolium-bromide (MTT) assay, There was a marked variation in antileukemic activity of both agents among the patient samples. The median LC50 (drug concentration lethal to 50% of the ALL cells) for PRD phosphate was 3.50 |jlM, for DXM phosphate 0,20 jxM. The individu ally calculated ratios oftheLCSO values for PRD and DXM phosphate showed a large range from 0.7 to > 5 0 0 ; with a median of 16.2. This 16-fold difference could not be explained by differences betw een these glucocorticoids in stability, hy drolysis into unesterified drug, adhesion to the wall o f the microculture plates, or protein bind ing. ALL cells were cross-resistant to PRD and DXM phosphate (correlation coefficient = 0.85, P < 0.000001).W e conclude that the in vitro antileukemic activity o f DXM phosphate is median 16-fold higher than that of PRD phosphate, which contrasts to the generally assumed factor of 7, Based on the higher potency of DXM, and its more favorable pharmacokinetics as reported in the literature, DXM may be pre ferred to PRD as the glucocorticoid in the treatment of ALL.

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Corticosteroid-Induced Dermal Atrophy in The Rat

Cited by 31 publications

References 18 publications

Test systems for the determination of glucocorticoid receptor ligand induced skin atrophy

Test systems for the determination of glucocorticoid receptor ligand induced skin atrophy

Effect of Intravenously Infused Dexamethasone on Collagen Metabolism in Skin of Merino Sheep

Comparison of the antileukemic activity in vitro of dexamethasone and prednisolone in childhood acute lymphoblastic leukemia

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