Influence of the PDE5 inhibitor tadalafil on redox status and antioxidant defense system in C2C12 skeletal muscle cells
Influence of the PDE5 inhibitor tadalafil on redox status and antioxidant defense system in C2C12 skeletal muscle cells
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DOI：
10.1007/s12192-017-0778-9
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发表时间：
2017-05-01
影响因子：
3.8
通讯作者：
Di Luigi, Luigi
中科院分区：
文献类型：
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作者：
Duranti, Guglielmo;Ceci, Roberta;Di Luigi, Luigi
磷酸二酯酶5型抑制剂（PDE 5Is）因其对男性勃起功能障碍的有益作用而广为人知，似乎也对代谢产生了有利的影响。他达拉非暴露增加C2 C12骨骼肌细胞的氧化代谢。脂肪酸（FA）代谢的增加，需要更多的氧气，可能会导致更大的活性氧（ROS）释放作为副产物，从而导致氧化还原失衡。本研究的目的是确定PDE 5I他达拉非如何影响骨骼肌细胞的氧化还原状态，以匹配不断增加的氧化代谢。为此，用他达拉非处理分化的C2 C12骨骼肌细胞，并分析总抗氧化能力（TAC）和谷胱甘肽水平作为氧化还原状态的标志物;参与抗氧化防御的超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GPx）的酶活性;以及脂质过氧化（TBARS）和蛋白质羰基（PrCar）作为氧化损伤的标志物。他达拉非可增加细胞内总谷胱甘肽（tGSH）、CAT、SOD和GPx酶活性，而TAC无变化。观察到氧化还原状态的扰动，如通过还原/氧化谷胱甘肽（GSH/GSSG）之间的比率的降低所示。然而，它没有引起TBARS和PrCar水平的任何变化，可能是由于抗氧化酶网络的增强。综上所述，这些数据表明，他达拉非除了改善氧化代谢外，还可能通过增强酶抗氧化系统能力对骨骼肌细胞有益。
Phosphodiesterase type 5 inhibitors (PDE5Is), widely known for their beneficial effects onto male erectile dysfunction, seem to exert favorable effects onto metabolism as well. Tadalafil exposure increases oxidative metabolism of C2C12 skeletal muscle cells. A rise in fatty acid (FA) metabolism, requiring more oxygen, could induce a larger reactive oxygen species (ROS) release as a byproduct thus leading to a redox imbalance. The aim of this study was to determine how PDE5I tadalafil influences redox status in skeletal muscle cells to match the increasing oxidative metabolism. To this purpose, differentiated C2C12 skeletal muscle cells were treated with tadalafil and analyzed for total antioxidant capacity (TAC) and glutathione levels as marker of redox status; enzyme activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) engaged in antioxidant defense; and lipid peroxidation (TBARS) and protein carbonyls (PrCar) as markers of oxidative damage. Tadalafil increased total intracellular glutathione (tGSH), CAT, SOD, and GPx enzymatic activities while no changes were found in TAC. A perturbation of redox status, as showed by the decrease in the ratio between reduced/oxidized glutathione (GSH/GSSG), was observed. Nevertheless, it did not cause any change in TBARS and PrCar levels probably due to the enhancement in the antioxidant enzymatic network. Taken together, these data indicate that tadalafil, besides improving oxidative metabolism, may be beneficial to skeletal muscle cells by enhancing the enzymatic antioxidant system capacity.