scholarly journals Differential Regulation of Damage-Associated Molecular Pattern Release in a Mouse Model of Skeletal Muscle Ischemia/Reperfusion Injury

2021 ◽  
Vol 12 ◽  
Author(s):  
Hiroaki Furubeppu ◽  
Takashi Ito ◽  
Midori Kakuuchi ◽  
Tomotsugu Yasuda ◽  
Chinatsu Kamikokuryo ◽  
...  

BackgroundSkeletal muscle ischemia/reperfusion (I/R) injury is an important clinical issue that can cause remote organ injury. Although its pathogenesis has not been fully elucidated, recent studies have suggested that damage-associated molecular patterns (DAMPs) are mediators of remote organ injury in sterile inflammation. The purpose of this study was to investigate the possible involvement of DAMPs, including the nuclear proteins high-mobility group box 1 (HMGB1) and histone H3, in the pathogenesis of skeletal muscle I/R injury in mice.MethodsHindlimb ischemia was induced in mice through bilateral ligation of inguinal regions using rubber grommets. Reperfusion was induced by cutting the rubber grommets after 2–12 h of ischemic period. Survival rates, localization of HMGB1 and histone H3 in the gastrocnemius muscle, and circulating HMGB1 and histone H3 levels were analyzed. The effect of anti-HMGB1 and anti-histone H3 antibodies on survival was analyzed in mice with I/R injury.ResultsAll mice with hindlimb ischemia survived for at least 36 h, while all mice died within 24 h if the hindlimbs were reperfused after ischemia for 4–12 h. Immunohistochemical analysis revealed that HMGB1 translocated from the nucleus to the cytoplasm in the ischemic gastrocnemius muscle, while histone H3 was confined to the nucleus. Accordingly, serum HMGB1 levels were significantly elevated in mice with hindlimb I/R compared with normal mice or mice with hindlimb ischemia (P < 0.05). Serum histone H3 levels were not elevated after I/R. Treatment with anti-HMGB1 antibodies significantly improved survival of mice with hindlimb I/R injury compared with control antibodies (P < 0.05).ConclusionsHMGB1, but not histone H3, translocated to the cytoplasm during skeletal muscle ischemia, and was released into the systemic circulation after reperfusion in mice with I/R injury. Treatment with anti-HMGB1 antibodies partially improved survival.

2021 ◽  
Vol 28 (9) ◽  
pp. 1671
Author(s):  
Levent Demirtas ◽  
Cebrail Gursul ◽  
Ahmet Gurbuzel ◽  
Ilyas Sayar ◽  
Mehmet Gurbuzel ◽  
...  

PLoS ONE ◽  
2008 ◽  
Vol 3 (4) ◽  
pp. e2026 ◽  
Author(s):  
Rongqian Wu ◽  
Weifeng Dong ◽  
Youxin Ji ◽  
Mian Zhou ◽  
Corrado P. Marini ◽  
...  

2005 ◽  
Vol 59 (2) ◽  
pp. 527
Author(s):  
Ernest A. Gonzalez ◽  
Rosemary A. Kozar ◽  
James W. Suliburk ◽  
David W. Mercer ◽  
Frederick A. Moore

2002 ◽  
Vol 13 (3) ◽  
pp. 144-150
Author(s):  
Yuriko Matsuura ◽  
Kaoru Koike ◽  
Atsuko Tsujii ◽  
Saeed Samarghandian ◽  
Shigeki Kushimoto ◽  
...  

2012 ◽  
Vol 27 (9) ◽  
pp. 611-615 ◽  
Author(s):  
Mohammad Ashrafzadeh Takhtfooladi ◽  
Amirali Jahanshahi ◽  
Gholamreza Jahanshahi ◽  
Amir Sotoudeh ◽  
Hamed Ashrafzadeh Takhtfooladi ◽  
...  

PURPOSE: To investigate whether N-acetylcysteine has a protective effect against renal injury as a remote organ after skeletal muscle ischemia-reperfusion in rats. METHODS: Twenty Wistar male rats were divided randomly into two experimental groups: group ischemia-reperfusion (group I) and group ischemia-reperfusion + N-acetylcysteine (group II). After ketamine and xylazine anesthesia, femoral artery was exposed. All animals were undergone 2h of ischemia by occlusion femoral artery and 24h of reperfusion. Rats that were treated with N-acetylcysteine given IV at a dose of 150 mg/kg-¹, immediately before reperfusion. After 24h of reperfusion, the blood samples were collected and submitted for evaluation of plasmatic urea, creatinine values and then rats were euthanized and left kidney harvested for histopathological analysis under light microscopy. RESULTS: The urea (35±7.84 mg.dL-1), creatinine (1.46±0.47 mg.dL-1) values were significantly lower in group II (P=0.000). Renal histopathologic study in group I showed extensive distal and proximal tubular cells necrosis and sloughing of epithelial cells into the tubular lumen, cast formation in tubule and glomerul, glomerul fibrosis and hemorrhage. Histopathologically, there was a significant difference (p=0.037) between two groups. CONCLUSION: The N-acetylcysteine was able to decrease renal injury induced by skeletal muscle ischemia reperfusion in rats.


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