Beneficial Effect of the Active Form of Vitamin D₃ against LPS-induced DIC but not against Tissue-factor-induced DIC in Rat Models

Summary

1 α,25-dihydroxyvitamin D₃ (active form of vitamin D₃; vitamin D₃) has been reported to induce the upregulation of thrombomodulin and downregulation of tissue factor (TF) on monocytes. The possibility exists that vitamin D₃ prevents the development of disseminated intravascular coagulation (DIC). In particular, monocyte TF production plays an important role in the pathophysiology of DIC in septic patients. We have attempted to determine whether vitamin D₃ is effective against DIC in a rat model induced by lipopolysaccharides (LPS) (30 mg/kg, 4 h) or TF (3.75 U/kg, 4 h) using selective hemostatic parameters, markers of organ dysfunction and pathological findings (assessment of glomelular fibrin deposition). Vitamin D₃ was administered orally each day at a dose of 2.0 mg/kg/day for 3 days, or low molecular weight heparin (LMWH 200 u/kg; I. V.) was given 10 min before the injection of TF or LPS in each treatment group. Vitamin D₃ was effective against DIC in the rat model induced by LPS only, whereas LMWH was effective against DIC in both rat models induced by either TF or LPS. The anti-DIC effect of vitamin D₃ was equal to (or more potent than) that of LMWH. The results suggested that vitamin D₃ was useful for the treatment of LPS-induced DIC, and that the assessment of a drug’s efficacy should be done carefully given the markedly different results obtained according to the agents used to induce DIC.

Keywords

Disseminated intravascular coagulation - tissue factor - lipopolysaccharide - active form of vitamin D₃

• References

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