[in Japanese]

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It is well known that the administration of all-trans retinoic acid (ATRA) improves the disseminated intravascular coagulation syndrome (DIC) in patients with acute promyelocytic leukemia (APL). It has also been shown that additions of ATRA to an APL cell line and human umbilical venous endothelial cells up-regulate the expression of thrombomodulin (TM), and down-regulate that of tissue factor (TF) in vitro. To investigate whether or not administration of ATRA improves the endotoxin-induced DIC, we administrated ATRA to the endotoxin-induced experimental DIC model rats and investigated plasma levels of several coagulation markers, kidney functions, the lethal rate and fibrin thrombus formation in the renal glomeruli. The experimental DIC model was induced in rats by administration of lipopolysaccharide (LPS) at a dose of 30mg/kg/4hr from the tail vein. ATRA was given orally at a dose of 20mg once a day for 7 days before the administration of LPS. Decreased plasma levels of fibrinogen (Fdg) and increased D-dimer (DD), thrombin-antithrombin III complex (TAT), creatinine (Cr) and alanine aminotransferase (ALT) in these rats were significantly inhibited by the administration of ATRA (p<0.05, 0.05, 0.05, 0.05 and 0.05, respectively). The administration of ATRA also significantly inhibited the fibrin thrombus formation and increased the expression of TM in the renal glomeruli as compared with the control given LPS alone. These changes in plasma levels of Fbg, DD, TAT, ALT and Cr, and fibrin thrombus formation were all significantly inhibited and the lethal rate was improved by the injection of ATRA. These results suggest that ATRA is able to prevent the endotoxin-induced DIC and to improve the lethal rate in rats.

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