Dexamethasone 21-phosphate disodium salt

Dexamethasone phosphate disodium is a glucocorticoid receptor agonist.

Signaling Pathways >> GPCR/G Protein >> Glucocorticoid Receptor

Research Areas >> Inflammation/Immunology

Glucocorticoid receptor[1]

Dexamethasone regulates several transcription factors, including activator protein-1, nuclear factor-AT, and nuclear factor-kB, leading to the activation and repression of key genes involved in the inflammatory response[1]. Dexamethasone potently inhibits granulocyte-macrophage colony stimulating factor (GM-CSF) release from A549 cells with EC50 of 2.2 nM. Dexamethasone (EC50=36 nM) induces transcription of the β2-receptor is found to correlate with glucocorticoid receptor (GR) DNA binding and occurred at 10-100 fold higher concentrations than the inhibition of GM-CSF release. Dexamethasone (IC50=0.5 nM) inhibits a 3×κB (NF-κB, IκBα, and I-κBβ), which is associated with inhibition of GM-CSF release[2].

Treatment with Dexamethasone at a dose of 2×5 mg/kg efficiently inhibits lipopolysaccharide (LPS)-induced inflammation. In our experimental system, treatment with a single dose of Dexamethasone 10 mg/kg (i.p.) significantly decreases recruitment of granulocytes as well as spontaneous production of oxygen radicals compared with animals expose to LPS and injected with solvent alone (saline). The effects are statistically significant when administered both 1 h before and 1 h after inhalation of LPS. The number of granulocytes in BALF decreased to levels comparable to healthy animals (given an aerosol of water)[3]. Rats treated with Dexamethasone consume less food and weighed less than control rats. Treated rats also weigh less than pair-fed animals though their food intake is similar. Five days of Dexamethasone injection result in a significant increase in both the liver mass (+42%) and the liver to body weight ratio (+65%). The wet weight of gastrocnemius muscle decreases 20% after 5 days of treatment, but it remains unaffected relative to body weight (g/100 g body weight), indicating that muscle weight loss paralleled body weight loss[4].

Rats: Male Sprague-Dawley rats are used. Dexamethasone-treated rats are injected intraperitoneally once daily with Dexamethasone (1.5 mg/kg body weight) for 5 days and are allowed to feed ad libitum. Control rats receive no treatment and are fed ad libitum. In order to take into account the decrease in food intake induced by Dexamethasone treatment, a third group of pair-fed rats are used. These rats are provided with the same amount of food as Dexamethasone-injected rats and are treated with a daily isovolumic intraperitoneal injection of NaCl (0.9%) for 5 days. After the final injection of Dexamethasone or NaCl, the animals are fasted overnight prior to being killed by decapitation[4]. Mice: Female C57Bl/6JBom mice (age 10-12 weeks) are used in all experiments. Dexamethasone is administered as a single injection of 1 or 10 mg/kg. Dexamethasone is dissolved in saline and 400 μL are injected intraperitoneally, either 1 h before or 1 h after LPS exposure. In one experiment, N-acetylcysteine (NAC) (100 and 500 mg/kg) is injected successively every 4-5 h, starting 1 h before challenge (five injections in total). A control group of LPS-exposed animals are injected intraperitoneally with solvent alone (saline). Intratracheal administration is performed by instillation of 100 μL NAC (50, 100 or 500 mg/kg) or Dexamethasone (10 mg/kg) into the lungs of mice anaesthetized with 15 mg/kg Rapinovet (i.v.)[3].

[1]. LaLone CA, et al. Effects of a glucocorticoid receptor agonist, Dexamethasone, on fathead minnow reproduction, growth, and development. Environ Toxicol Chem. 2012 Mar;31(3):611-22.

[2]. Adcock IM, et al. Ligand-induced differentiation of glucocorticoid receptor (GR) trans-repression and transactivation: preferential targetting of NF-kappaB and lack of I-kappaB involvement. Br J Pharmacol. 1999 Jun;127(4):1003-11.

[3]. Rocksén D, et al. Differential anti-inflammatory and anti-oxidative effects of Dexamethasone and N-acetylcysteine in endotoxin-induced lung inflammation. Clin Exp Immunol. 2000 Nov;122(2):249-56.

[4]. Roussel D, et al. Dexamethasone treatment specifically increases the basal proton conductance of rat liver mitochondria. FEBS Lett. 2003 Apr 24;541(1-3):75-9.

Hydrocortisone | Mifepristone | Corticosterone | Prednisone | (20S)-Protopanaxatriol | Fluticasone propionate | Triamcinolone | Cortisone | AL 082D06 | Glucocorticoid receptor agonist | Mapracorat | Ciclesonide | Beclometasone dipropionate | Clobetasol propionate | CORT-108297

MOLECULAR FORMULA :

C22-H28-F-O8-P.2Na

MOLECULAR WEIGHT :

516.45

WISWESSER LINE NOTATION :

L E5 B666 OV AHTTT&J A1 BF CQ E1 FV1OPWO FQ G1 &-NA- 2

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Human - infant

DOSE/DURATION :

1500 ug/kg/3D-I

TOXIC EFFECTS :

Brain and Coverings - recordings from specific areas of CNS

REFERENCE :

LANCAO Lancet. (7 Adam St., London WC2N 6AD, UK) V.1- 1823- Volume(issue)/page/year: 1,632,1987

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

320 mg/kg

TOXIC EFFECTS :

Gastrointestinal - other changes

REFERENCE :

LANCAO Lancet. (7 Adam St., London WC2N 6AD, UK) V.1- 1823- Volume(issue)/page/year: 1,1035,1986

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Human - child

DOSE/DURATION :

1 mg/kg

TOXIC EFFECTS :

Gastrointestinal - peritonitis

REFERENCE :

AJEMEN American Journal of Emergency Medicine. (WB Saunders, Philadelphia, PA) V.1- 1983- Volume(issue)/page/year: 10,268,1992

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

357 ug/kg

TOXIC EFFECTS :

Gastrointestinal - peritonitis

REFERENCE :

AJEMEN American Journal of Emergency Medicine. (WB Saunders, Philadelphia, PA) V.1- 1983- Volume(issue)/page/year: 10,268,1992

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

1800 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

ATSUDG Archives of Toxicology, Supplement. (Springer-Verlag New York, Inc., Service Center, 44 Hartz Way, Secaucus, NJ 07094) No.1- 1978- Volume(issue)/page/year: 7,90,1984

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

550 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

ATSUDG Archives of Toxicology, Supplement. (Springer-Verlag New York, Inc., Service Center, 44 Hartz Way, Secaucus, NJ 07094) No.1- 1978- Volume(issue)/page/year: 7,90,1984

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

932 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: -,785,1995 ** REPRODUCTIVE DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

7500 ug/kg

SEX/DURATION :

female 6-15 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetal death

REFERENCE :

BCFAAI Bollettino Chimico Farmaceutico. (Societa Editoriale Farmaceutica, Via Ausonio 12, 20123 Milan, Italy) V.33- 1894- Volume(issue)/page/year: 119,391,1980

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

1 mg/kg

SEX/DURATION :

female 6-15 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

REFERENCE :

BCFAAI Bollettino Chimico Farmaceutico. (Societa Editoriale Farmaceutica, Via Ausonio 12, 20123 Milan, Italy) V.33- 1894- Volume(issue)/page/year: 119,391,1980

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

400 ug/kg

SEX/DURATION :

female 19-20 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

REFERENCE :

PEDIAU Pediatrics. (American Academy of Pediatrics, P.O. Box 1034, Evanston, IL 60204) V.1- 1948- Volume(issue)/page/year: 65,287,1980

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

10 mg/kg

SEX/DURATION :

female 6-15 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Effects on Embryo or Fetus - fetal death

REFERENCE :

BCFAAI Bollettino Chimico Farmaceutico. (Societa Editoriale Farmaceutica, Via Ausonio 12, 20123 Milan, Italy) V.33- 1894- Volume(issue)/page/year: 119,391,1980

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

2 mg/kg

SEX/DURATION :

female 6-15 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

REFERENCE :

BCFAAI Bollettino Chimico Farmaceutico. (Societa Editoriale Farmaceutica, Via Ausonio 12, 20123 Milan, Italy) V.33- 1894- Volume(issue)/page/year: 119,391,1980

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

12800 ug/kg

SEX/DURATION :

female 11-14 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

REFERENCE :

SEIJBO Senten Ijo. Congenital Anomalies. (Nippon Senten Ijo Gakkai, c/o Kinki Daigaku Igakubu Kaibagaku Kyoshitsu, 380 Nishiyama, Sayama-cho, Mirami-Kawachi-gun, Osaka-fu, Japan) V.1-26, 1960-86. For publisher information, see CGANE7. Volume(issue)/page/year: 13,245,1973

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

130 ug/kg

SEX/DURATION :

female 6-18 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetal death

REFERENCE :

BCFAAI Bollettino Chimico Farmaceutico. (Societa Editoriale Farmaceutica, Via Ausonio 12, 20123 Milan, Italy) V.33- 1894- Volume(issue)/page/year: 119,391,1980

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

650 ug/kg

SEX/DURATION :

female 6-18 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

REFERENCE :

BCFAAI Bollettino Chimico Farmaceutico. (Societa Editoriale Farmaceutica, Via Ausonio 12, 20123 Milan, Italy) V.33- 1894- Volume(issue)/page/year: 119,391,1980

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

DOSE :

9 mg/kg

SEX/DURATION :

female 21-26 day(s) after conception

TOXIC EFFECTS :

Reproductive - Maternal Effects - parturition Reproductive - Effects on Embryo or Fetus - fetal death

REFERENCE :

JOENAK Journal of Endocrinology. (Biochemical Soc. Book Depot, POB 32, Commerce Way, Colchester, Essex CO2 8HP, UK) V.1- 1939- Volume(issue)/page/year: 64,363,1975

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

DOSE :

300 ug/kg

SEX/DURATION :

female 25-27 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - gastrointestinal system

REFERENCE :

JSGRA2 Journal of Surgical Research. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1961- Volume(issue)/page/year: 57,274,1994

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Parenteral

DOSE :

8 mg/kg

SEX/DURATION :

female 11-14 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) Reproductive - Specific Developmental Abnormalities - body wall

REFERENCE :

ANIFAC Annales de Chirurgie Infantile. (Paris, France) V.1- 1960(?)- Volume(issue)/page/year: 3,73,1962

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Parenteral

DOSE :

8 mg/kg

SEX/DURATION :

female 11-14 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Effects on Embryo or Fetus - fetal death

REFERENCE :

ANIFAC Annales de Chirurgie Infantile. (Paris, France) V.1- 1960(?)- Volume(issue)/page/year: 3,73,1962

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Parenteral

DOSE :

4 mg/kg

SEX/DURATION :

female 11 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Fertility - abortion

REFERENCE :

ANIFAC Annales de Chirurgie Infantile. (Paris, France) V.1- 1960(?)- Volume(issue)/page/year: 3,73,1962

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

DOSE :

145 ug/kg

SEX/DURATION :

female 20 week(s) after conception

TOXIC EFFECTS :

Reproductive - Maternal Effects - parturition

REFERENCE :

AAAHAN Australian Journal of Experimental Agriculture and Animal Husbandry. (Commonwealth Scientific and Industrial Research Organization, 314 Albert St., E. Melbourne, Vic. 3002, Australia) V.1- 1961- Volume(issue)/page/year: 16,462,1976

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

DOSE :

2739 ug/kg

SEX/DURATION :

female 21 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Maternal Effects - other effects

REFERENCE :

JRFSAR Journal of Reproduction and Fertility, Supplement. (Biochemical Soc. Book Depot, POB 32, Commerce Way, Colchester, Essex CO2 8HP, UK) No.1- 1966- Volume(issue)/page/year: 32,247,1982

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

DOSE :

1304 ug/kg

SEX/DURATION :

female 10 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Fertility - other measures of fertility

REFERENCE :

JRFSAR Journal of Reproduction and Fertility, Supplement. (Biochemical Soc. Book Depot, POB 32, Commerce Way, Colchester, Essex CO2 8HP, UK) No.1- 1966- Volume(issue)/page/year: 32,247,1982 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOHS - National Occupational Hazard Survey (1974) NOHS Hazard Code - 82148 No. of Facilities: 67 (estimated) No. of Industries: 2 No. of Occupations: 1 No. of Employees: 680 (estimated) NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - 82148 No. of Facilities: 363 (estimated) No. of Industries: 2 No. of Occupations: 7 No. of Employees: 16943 (estimated) No. of Female Employees: 14180 (estimated)