Hirudin ameliorates intestinal radiation toxicity in the rat: support for thrombin inhibition as strategy to minimize side‐effects after radiation therapy and as countermeasure against radiation exposure

Abstract

To cite this article: Wang J, Zheng H, Ou X, Albertson CM, Fink LM, Herbert J-M, Hauer-Jensen M. Hirudin ameliorates intestinal radiation toxicity in the rat: support for thrombin inhibition as strategy to minimize side-effects after radiation therapy and as countermeasure against radiation exposure.

Essential Role of Plasminogen Activator Inhibitor Type-1 in Radiation Enteropathy

“…A large number of strategies in experimental models show that the reduction of late effects is associated with an improvement in acute effects. [23][24][25] Our results suggest that pharmacological strategies aimed to inhibit PAI-1 activity could prevent acute and late effects of radiation-induced normal tissue damage. PAI-1 is upregulated in fibrotic diseases including hepatic, pulmonary, or renal fibrosis, and PAI-1 knockout mice are protected against fibrosis in various models.…”

Simvastatin Ameliorates Radiation Enteropathy Development After Localized, Fractionated Irradiation by a Protein C-Independent Mechanism

“…In the acute phase, radiation increases endothelial cell permeability and expression of chemokines and adhesion molecules, and causes loss of vascular thromboresistance (3,4). Radiation-induced loss of vascular thromboresistance is a result of decreased fibrinolytic activity (24), increased expression of tissue factor (TF) (25,26) and von Willebrand factor (27), and decreased expression of prostacyclin (28) and TM (5,(29)(30)(31). TM is a transmembrane glycoprotein, located on the luminal surface of endothelial cells in most normal blood vessels.…”

Radiation-Induced Activation of TGF-β Signaling Pathways in Relation to Vascular Damage in Mouse Kidneys

“…APC attenuates the intrinsic coagulation cascade by inhibiting factors Va and VIIIa, thereby limiting further thrombin generation (12). Studies from our laboratory demonstrate that thrombin inhibition by anticoagulant treatment suppresses radiation damage in rat intestine (13), and that recombinant APC administration provides radiation lethality protection in mice (8). In addition, the N-terminal lectin-like domain of Solulin and APC have antioxidant and anti-inflammatory properties (14)(15)(16)(17), which are well known for their ability to counteract radiation injury.…”