Herminghaus Anna, Buitenhuis Albert J, Schulz Jan, Truse Richard, Vollmer Christian, Relja Borna, Bauer Inge, Picker Olaf
Department of Anaesthesiology, University Hospital Duesseldorf, Duesseldorf, Germany.
Experimental Radiology, Department of Radiology and Nuclear Medicine, Otto von Guericke University, Magdeburg, Germany.
Front Med (Lausanne). 2020 Aug 21;7:463. doi: 10.3389/fmed.2020.00463. eCollection 2020.
Studies suggest that indomethacin (Indo) exhibits detrimental changes in the small intestine (microvascular disorder, villus shortening, and epithelial disruption), mainly due to mitochondrial uncoupling. The effects of Indo on colon and liver tissue are unclear. The aim of this study was to determine the effects of Indo on mitochondrial respiration in colonic and hepatic tissue. Mitochondrial oxygen consumption was assessed in colon and liver homogenates from healthy rats. Homogenates were incubated without drug (control) or Indo (colon: 0.36, 1, 30, 179, 300, 1,000, 3,000 μM; liver: 0.36, 1, 3, 10, 30, 100, 179 μM; = 6). State 2 (substrate-dependent) and state 3 (ADP-dependent respiration) were evaluated with respirometry. The respiratory control index (RCI) was derived and the ADP/O ratio was calculated. Data presented as % of control, min/median/max, Kruskal-Wallis+Dunn's correction, < 0.05 vs. control. Indo had no effect on RCI of colonic mitochondria. ADP/O ratio increased in complex I at concentrations of 1,000 and 3,000 μM (Indo 1,000 μM: 113.9/158.9/166.9%; Indo 3,000 μM: 151.5/183.0/361.5%) and in complex II at concentrations of 179 and 3,000 μM vs. control (179 μM: 111.3/73.1/74.9%; 3,000 μM: 132.4/175.0/339.4%). In hepatic mitochondria RCI decreased at 179 μM for both complexes vs. control (complex I: 25.6/40.7/62.9%, complex II: 57.0/73.1/74.9%). The ADP/O ratio was only altered in complex I at a concentration of 179 μM Indo vs. control (Indo 179 μM: 589.9/993.7/1195.0 %). Indo affected parameters of mitochondrial function in an organ-specific and concentration-dependent manner. In colonic tissue, RCI remained unaltered whereas the ADP/O ratio increased. Indo at the highest concentration decreased the RCI for both complexes in hepatic mitochondria. The large increase in ADP/O ratio in complex I at the highest concentration likely reflects terminal uncoupling.
研究表明，吲哚美辛（Indo）会使小肠出现有害变化（微血管紊乱、绒毛缩短和上皮破坏），主要原因是线粒体解偶联。Indo对结肠和肝脏组织的影响尚不清楚。本研究的目的是确定Indo对结肠和肝脏组织中线粒体呼吸的影响。在来自健康大鼠的结肠和肝脏匀浆中评估线粒体氧消耗。匀浆在无药物（对照）或Indo（结肠：0.36、1、30、179、300、1000、3000 μM；肝脏：0.36、1、3、10、30、100、179 μM；n = 6）的情况下孵育。用呼吸测定法评估状态2（底物依赖性）和状态3（ADP依赖性呼吸）。得出呼吸控制指数（RCI）并计算ADP/O比率。数据以对照的百分比、最小值/中位数/最大值表示，采用Kruskal-Wallis + Dunn校正，P < 0.05表示与对照相比有差异。Indo对结肠线粒体的RCI没有影响。在复合物I中，浓度为1000和3000 μM时ADP/O比率增加（Indo 1000 μM：113.9/158.9/166.9%；Indo 3000 μM：151.5/183.0/361.5%），在复合物II中，浓度为179和3000 μM时与对照相比增加（179 μM：111.3/73.1/74.9%；3000 μM：132.4/175.0/339.4%）。在肝脏线粒体中，两种复合物在179 μM时RCI均低于对照（复合物I：25.6/40.7/62.9%，复合物II：57.0/73.1/74.9%）。仅在Indo浓度为179 μM时，复合物I中的ADP/O比率与对照相比发生改变（Indo 179 μM：589.9/993.7/1195.0%）。Indo以器官特异性和浓度依赖性方式影响线粒体功能参数。在结肠组织中，RCI保持不变，而ADP/O比率增加。Indo在最高浓度时降低了肝脏线粒体中两种复合物的RCI。复合物I在最高浓度时ADP/O比率的大幅增加可能反映了终末解偶联。
