Edaravone prevents bowel infarction after acute superior mesenteric artery thromboembolism using autologous fibrin clots in a rabbit model

Abstract

The aim of this study was to evaluate the effects of intra-arterial administration of edaravone after superior mesenteric artery (SMA) thromboembolism in a rabbit model. 24 Japanese white rabbits were randomly allocated to a urokinase group (group U) and a urokinase with edaravone group (group E). A further three rabbits, which were administered an autologous blood clot alone, served as a control group (group C). A 4-Fr sheath was inserted into an SMA. An autologous blood clot was administered to an SMA (group C). After 45 min, urokinase (6000 IU) and heparin (250 IU) were administered through the catheter, either alone (group U) or in conjuction with edaravone (0.5 mg kg(-1)) (group E). In eight rabbits from each of groups U and E, 6 h after reperfusion, the small intestine was harvested and divided into five equal parts. The degree of intestinal tissue injury in each part was rated on a scale of 0-8. After 1 week, survival times and blood biochemistry data were compared among rabbits in group U (four rabbits), group E (four rabbits) and group C (three rabbits), and significant differences (p<0.05) were recorded. Intestinal mucosal damage was significantly greater in group U (5.8 +/- 1.5) than in group E (2.9 +/- 0.7). Survival time tended to be longer in group E (p>0.4, not significant compared with group U). Liver and kidney function showed signs of deterioration over time whether or not edaravone was administered, but administration of edaravone reduced intestinal mucosal damage. An increase in survival rate requires improvements in evaluation methods to enable identification of ischaemic areas.

Beyond neurological disease: New targets for edaravone (Review)

“…I/R-related injuries, which occur when a thrombus is removed, result in marked intestinal tissue damage (40). Oxygen free radicals trigger neutrophil infiltration into ischemic intestinal tissues (41). In rats, edaravone reduced I/R-induced small intestine injury; the levels of intraluminal protein and hemoglobin, which are markers of mucosal injury; TBA-reactive substances and tissue-associated MPO activity; protein and mRNA levels of cytokine-induced neutrophil chemoattractant 1 (CINC-1; a member of the IL-8 family; and intestinal erosion and bleeding (42).…”

“…In that study, CINC-1 protein and CINC-1 mRNA levels increased with I/R injury and were reduced by treatment with edaravone. Meanwhile, in rabbits with induced acute superior mesenteric artery thromboembolism using autologous fibrin clots, edaravone was reported to prevent bowel infarction, extend survival time, and reduce mucosal damage (41).…”

Does the concomitant intra-arterial injection of asialoerythropoietin and edaravone mitigate ischaemic mucosal damage after acute superior mesenteric artery thromboembolism in a rabbit autologous fibrin clot model?

“…Animal studies on the mitigation of small intestine damage found that edaravone decreases the degree of I-R-mediated mucosal tissue injury [5][6][7]. Elsewhere, we showed that, in a rabbit ASMAT model that introduced autologous fibrin clots, thrombolysis via the intra-arterial administration of edaravone and urokinase contributed to a reduction in the degree of I-R injury to the small intestinal mucosa [4]. We attributed the failure of edaravone to improve the survival time to inadequate thrombolysis in some areas of the intestinal mucosa and postulated that damage caused by ischaemia rather than reperfusion resulted in critical intestinal injury (e.g.…”

“…An important factor in the high mortality of ASMAT patients is the generation of active oxygen by ischaemia-reperfusion (I-R) injury. We and others [2][3][4] have reported that the administration of oxygen free radical scavengers, such as superoxide dismutase or dimethylthiourea, reduces the degree of I-R injury in animal models. Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-1; norphenazone; MCI-186), a potent scavenger of hydroxyl and peroxyl radicals, inhibits lipid peroxidation via its antioxidant activity.…”

“…We attributed the failure of edaravone to improve the survival time to inadequate thrombolysis in some areas of the intestinal mucosa and postulated that damage caused by ischaemia rather than reperfusion resulted in critical intestinal injury (e.g. infarction) [4]. Asialoerythropoietin, a desialated form of erythropoietin that is non-hematopoietic but appears to retain extra-hematopoietic effects, is an analogous substance to erythropoietin [8,9] and exerts tissue-protective activities [9][10][11][12][13].…”