Glucocorticoidの抗ショック作用の研究:第2報 : Dexamethasoneの抗エンドトキシン効果と血中濃度-エステル型間における比較
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We have reported that there was a significant difference in the anti-endotoxic potency between dexamethasone disodium phosphate (DM-P) and dexamethasone sodium sulfate (DM-S) in mice. In this report we shall try to compare the dose-dependent anti-endotoxic effect between DM-P and DM-S in mice and show whether there is any relationship between the serum concentration of free 17-OHCS following the intravenous administration of 2 mg/kg dexamethasone and the anti-endotoxic potency or not.<BR>1) Six hundred and eighty-nine young male mice of DDN strain (20-25g b.w.) were used. 3.2, 1.6, 0.8, 0.4, 0.2, 0.1, 0.05, 0.025, 0.0125 and 0.00625mg dexamethasone (DM-P or DM-S) and 0.5mg endotoxin (E-coli 0127 B8, Difco, USA) were intraperitoneally injected. 72 hours later survival rates were counted. Survival rates in the group administered DM-P were 73.3, 60.0, 53.3, 53.3, 60.0, 49.3, 62.5, 53.3, 40.0 and 46.6% respectively. In the group administered DM-S, survival rates were 20.0, 26.6, 6.6, 18.9, 16.6, 25.0, 23.2, 26.6, 14.2 and 19.3% respectively.<BR>2) Twenty-seven elective surgical patients were investigated concerning their serum concentration of 17-OHCS following the administration of 2mg/kg dexamethasone during surgery (9 control patients, 10 patients administered DM-P, 8 patients administered DM-S). Serum 17-OHCS was measured at the control state, 30 min., 60 min., 120 min. and 180 min. after the administration of DM by the Porter-Silber method. The serum concentration of free 17-OHCS was 11.3 ± 2.0μg/ dl at the control state, and that in the control group was 5.2 ± 2.3, 17.1 ± 4.4, 10.6 ± 3.2 and 11.1 ± 4.2μg/dl respectively. In the DM-P group, it measured 208.6 ± 18.8,151.7 ± 15.3,113.7 ± 15.2 and 107.8 ± 12.1μg/dl respectively. (mean ± s.e.m.) <BR>We concluded that there was a significant difference in anti-endotoxic potency between DM-P and DM-S, that the serum concentration of free 17-OHCS was significantly elevated after administration of 2mg/kg DM-P but not after DM-S, that there was a close correlation between the anti-endotoxic potency of DM and its free form serum concentration, and finally that the biological action of glucocorticoid was greatly influenced by its side chain.
- 日本内分泌学会の論文
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関連論文
- Glucocorticoidの抗ショック作用の研究:第2報 : Dexamethasoneの抗エンドトキシン効果と血中濃度-エステル型間における比較
- Glucocorticoidの抗ショック作用の研究:第I報 : Dexamethasoneのエステル型による抗エンドトキシン効果の相異