Teriflunomide treatment exacerbates cardiac ischemia reperfusion injury in isolated rat hearts.
Teriflunomide treatment exacerbates cardiac ischemia reperfusion injury in isolated rat hearts.
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DOI：
10.1007/s10557-022-07341-z
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发表时间：
2023-10
影响因子：
3.4
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中科院分区：
文献类型：
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以前的工作表明，通过特氟米特(TERI)抑制二氢罗酸脱氢酶(DHODH)可能在多种疾病模型中提供保护。到目前为止，人们对TERI对心脏的影响知之甚少。本研究旨在评价TERI对心肌缺血再灌注损伤的潜在作用。雄性和雌性大鼠心脏在朗宁多夫装置上进行全心缺血(25min)和再灌流(120min)。DMSO(VEH)或Teriflunomide(TERI)分别在诱导缺血前和再灌注期给予5min。采用已建立的方法测定左心室压力、心电图、冠脉流量和梗塞范围。线粒体呼吸通过呼吸计量仪进行评估。TERI心脏灌流在500-50 NM剂量范围内没有导致任何急性影响。然而，在缺血-再灌注损伤后，我们发现50 NM TERI处理的心脏心肌梗死发生率增加(p <； 0.001)。在50例接受TERI治疗的心脏中，我们还观察到在较早的时间点(p <； 0.001)收缩严重程度显著增加(p = 0.004)，以及冠脉流量(p = 0.037)、左心室压力发展(p = 0.025)和心率-压力乘积(p = 0.008)减少。50 NM TERI处理对线粒体呼吸无明显影响(p = 0.24-0.87)。这项研究表明，TERI治疗会导致心脏缺血再灌注后更多的负面结果，对高危人群使用TERI应该给予特别的考虑。
Previous work suggests that Dihydroorotate dehydrogenase (DHODH) inhibition via teriflunomide (TERI) may provide protection in multiple disease models. To date, little is known about the effect of TERI on the heart. This study was performed to assess the potential effects of TERI on cardiac ischemia reperfusion injury. Male and female rat hearts were subjected to global ischemia (25 min) and reperfusion (120 min) on a Langendorff apparatus. Hearts were given either DMSO (VEH) or teriflunomide (TERI) for 5 min prior to induction of ischemia and during the reperfusion period. Left ventricular pressure, ECG, coronary flow, and infarct size were determined using established methods. Mitochondrial respiration was assessed via respirometry. Perfusion of hearts with TERI led to no acute effects in any values measured across 500 pM–50 nM doses. However, following ischemia–reperfusion injury, we found that 50 nM TERI-treated hearts had an increase in myocardial infarction (p < 0.001). In 50 nM TERI-treated hearts, we also observed a marked increase in the severity of contracture (p < 0.001) at an earlier time-point (p = 0.004), as well as reductions in coronary flow (p = 0.037), left ventricular pressure development (p = 0.025), and the rate-pressure product (p = 0.008). No differences in mitochondrial respiration were observed with 50 nM TERI treatment (p = 0.24–0.87). This study suggests that treatment with TERI leads to more negative outcomes following cardiac ischemia reperfusion, and administration of TERI to at-risk populations should receive special considerations.
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影响因子：
5.4
作者：
Kloner RA;Hale SL;Dai W;Gorman RC;Shuto T;Koomalsingh KJ;Gorman JH 3rd;Sloan RC;Frasier CR;Watson CA;Bostian PA;Kypson AP;Brown DA
通讯作者：
Brown DA
DOI：
10.1016/s0969-2126(00)00077-0
发表时间：
2000-01-15
期刊：
STRUCTURE WITH FOLDING & DESIGN
影响因子：
--
作者：
Liu, SP;Neidhardt, EA;Clardy, J
通讯作者：
Clardy, J
影响因子：
21.1
作者：
Xiong, Rui;Zhang, Leike;Xu, Ke
通讯作者：
Xu, Ke
影响因子：
11.5
作者：
Bar-Or, Amit;Pachner, Andrew;Menguy-Vacheron, Francoise;Kaplan, Johanne;Wiendl, Heinz
通讯作者：
Wiendl, Heinz
影响因子：
4.5
作者：
Xuan J;Ren Z;Qing T;Couch L;Shi L;Tolleson WH;Guo L
通讯作者：
Guo L