Effect of argatroban on trinitrobenzene sulfonic acid‐induced colitis

Onomura, M.; Tsukada, Hideaki; Fukuda, Kazuhito; Kodama, Mitsuo; Nakamura, Hiroshi; Hosokawa, Munetaka; Ohya, Masaki; Seino, Yutaka

doi:10.1046/j.1440-1746.2000.02279.x

Cited by 6 publications

(6 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[3][4][5] These changes in coagulant-anticoagulant factors are accompanied by enhanced thrombus formation in microvessels of organs distant to the colon, such as skeletal muscle. 3,6,7 Although the contributions of different pro-(tissue factor, thrombin) and anti-(activated protein C) coagulants to colitis-enhanced extra-intestinal thrombosis have been evaluated, 3,6,7 the chemical and/or cellular signal produced by the inflamed colon that promotes thrombosis at distant sites remain undefined.…”

mentioning

confidence: 99%

Interleukin-1β Mediates the Extra-Intestinal Thrombosis Associated with Experimental Colitis

Yoshida

Russell

Senchenkova

et al. 2010

The American Journal of Pathology

View full text Add to dashboard Cite

Inflammatory bowel diseases (IBDs) are associated with an increased risk for thromboembolism, which is often manifested as deep vein thrombosis or pulmonary embolism, at extra-intestinal sites. Although some of the cytokines that contribute to IBD pathogenesis are also known to alter the coagulation pathway, it remains unclear whether these mediators also contribute to the extra-intestinal thrombosis often associated with IBD. The objective of this study is to evaluate the role of interleukin (IL)-1␤ in enhanced extra-intestinal thrombosis observed in mice with dextran sodium sulfate (DSS)-induced colitis. IL-1␤ concentrations were measured in plasma, colon, and skeletal muscle of wild-type (WT) control and colitic mice. Microvascular thrombosis was induced in cremaster muscle microvessels by using a light/dye injury model. The effects of exogenous IL-1␤ on thrombus formation were determined in control WT mice. DSS-induced thrombogenesis was evaluated in WT mice treated with an IL-1␤ antibody and in IL-1 receptor-deficient (IL-1r؊/؊ ) mice. DSS-induced colonic inflammation in WT mice was associated with enhanced thrombus formation in arterioles. IL-1␤ concentrations were elevated in inflamed colon and skeletal muscle. Exogenous IL-1␤ enhanced thrombosis in control mice in a dose-dependent manner. DSS colitic mice treated with the IL-1␤ antibody as well as IL1r ؊/؊ mice exhibited significantly blunted thrombogenic responses. These findings implicate IL-1␤ as a mediator of enhanced microvascular thromboses that occur in extra-intestinal tissues during colonic inflammation.

show abstract

mentioning

confidence: 99%

Interleukin-1β Mediates the Extra-Intestinal Thrombosis Associated with Experimental Colitis

Yoshida

Russell

Senchenkova

et al. 2010

The American Journal of Pathology

View full text Add to dashboard Cite

show abstract

“…The influence of anticoagulant strategies on the severity of gut inflammation has been examined previously in animal models of IBD. For example, the thrombin-directed drugs, heparin and argatroban, have significantly reduced macroscopic and histological damage, mucosal MPO activity and mucosal leukotriene B 4 levels (as a proinflammatory mediator) in rats with TNBS-induced colitis [ 14 , 15 ]. Similar protection against gut inflammation has been demonstrated following intracolonic administration of the low-molecular-weight heparin, CB-01-05, in rats with dinitrobenzene-induced colitis [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

Rivaroxaban Induces Mucosal Healing in a Rat Model of Trinitrobenzene Sulfonic Acid-Induced Colitis

Utku¹,

Karatay²,

Erdal³

et al. 2015

Med Princ Pract

View full text Add to dashboard Cite

Objective: This study was designed to identify the effect of rivaroxaban, a direct factor Xa inhibitor, on trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. Materials and Methods: Twenty-four female Wistar rats were divided into 4 groups of 6 each. Group 1 received TNBS + rivaroxaban, group 2 received TNBS + methylprednisolone, group 3 received TNBS and group 4 received a saline enema. Colitis was induced in the rats by the intracolonic administration of TNBS. Rivaroxaban and methylprednisolone were given by oral gavage daily for 7 days. The rats were killed 7 days after the induction of colitis. Results: Rivaroxaban and methylprednisolone significantly reduced gross damage and histopathological scores. Rivaroxaban was more effective than methylprednisolone in terms of microscopic mucosal healing. Rivaroxaban attenuated the accumulation of malonyldialdehyde (MDA) and transforming growth-factor β₁ (TGF-β₁) and the activites of myeloperoxidase (MPO), matrix metalloproteinase-3 and tissue inhibitor of metalloproteinases-1. Methylprednisolone reduced only the activity of MPO and the accumulation of MDA and TGF-β₁. Superoxide dismutase activity showed a restoration to normal levels after rivaroxaban and methylprednisolone administration. Conclusions: Rivaroxaban showed a therapeutic effect in the TNBS model of experimental colitis, and it seemed to be at least as effective as methylprednisolone. This effect may be brought about by the inhibition of oxidative stress and metalloproteinase activity associated with tissue injury and remodeling.

show abstract

“…However, emerging evidence from rodent models of chemically induced colitis (e.g., DSS, TNBS) suggest that the balance between anticoagulant and procoagulant factors is tipped in favor of coagulation and thrombosis. For example, thrombocytosis and increased plasma fibrinogen levels, along with a corresponding reduction in antithrombin III concentration, has been reported in rats with TNBS‐induced colitis 44. Similarly, thrombin‐antithrombin (TAT) complexes are 3 times higher in mice with DSS colitis compared to their control (noncolitic) counterparts, implicating an accelerated production of thrombin in the diseased mice 45.…”

Section: Evidence For Activation Of Coagulation and Enhanced Thrombosmentioning

confidence: 98%

“…The view that coagulation and inflammation are interdependent processes that propagate and amplify each other is also supported by studies that examined the influence of anticoagulant strategies on the severity of gut inflammation in animal models of IBD. For example, the thrombin‐directed drugs heparin and argatroban (interferes with the conversion of fibrinogen to fibrin by thrombin) have been shown to significantly reduce macroscopic and histologic damage, mucosal myeloperoxidase activity (a measure of neutrophil accumulation), and mucosal LTB4 levels in rats with TNBS‐induced colitis 44, 66. Similar protection against gut inflammation was recently demonstrated following intracolonic administration of the low‐molecular‐weight heparin CB‐01‐05 in rats with dinitrobenzene‐induced colitis 67.…”

Section: Dependence Of Inflammatory Response On Coagulation Pathways mentioning

confidence: 99%

Inflammatory bowel disease

Yoshida

Granger

2009

Inflammatory Bowel Diseases

114

View full text Add to dashboard Cite

Inflammatory bowel diseases (IBD) are associated with platelet activation and an increased risk for thromboembolism. While the mechanisms that underlie the altered platelet function and hypercoagulable state in IBD remain poorly understood, emerging evidence indicates that inflammation and coagulation are inter-dependent processes that can initiate a vicious cycle wherein each process propagates and intensifies the other. This review addresses the mechanisms that may account for the mutual activation of coagulation and inflammation during inflammation and summarizes evidence that implicates a role for platelets and the coagulation system in the pathogenesis of human and experimental IBD. The proposed link between inflammation and coagulation raises the possibility of targeting the inflammation-coagulation interface to reduce the morbidity and mortality associated with IBD.

show abstract

Effect of argatroban on trinitrobenzene sulfonic acid‐induced colitis

Cited by 6 publications

References 21 publications

Interleukin-1β Mediates the Extra-Intestinal Thrombosis Associated with Experimental Colitis

Interleukin-1β Mediates the Extra-Intestinal Thrombosis Associated with Experimental Colitis

Rivaroxaban Induces Mucosal Healing in a Rat Model of Trinitrobenzene Sulfonic Acid-Induced Colitis

Inflammatory bowel disease

Contact Info

Product

Resources

About