Matusovits Danica, Murlasits Zsolt, Kupai Krisztina, Baráth Zoltán, Kang Hsu Lin, Osváth Péter, Szűcs Miklós, Priksz Dániel, Juhász Béla, Radák Zsolt, Várkonyi Tamás, Pavo Imre, Pósa Anikó
Department of Prosthodontics, Faculty of Dentistry, University of Szeged, 6703 Szeged, Hungary.
Institute of Sport Science and Physical Education University of Pécs, 7601 Pécs, Hungary.
Antioxidants (Basel). 2023 May 20;12(5):1129. doi: 10.3390/antiox12051129.
(1) Background: In cardiovascular applications, paclitaxel inhibits smooth muscle cell proliferation and migration and significantly reduces the occurrence of restenosis and target lesion revascularization. However, the cellular effects of paclitaxel in the myocardium are not well understood; (2) Methods: Wistar rats were divided into four groups: control (CTRL), isoproterenol (ISO) treated (1 mg/kg) and two groups treated with paclitaxel (PAC), which was administrated (10 mg/kg/day) for 5 days by gavage/per os alone or in combination (ISO + PAC) 3 weeks after ISO treatment. Ventricular tissue was harvested 24 h later for measurements of heme oxygenase (HO-1), reduced glutathione (GSH), oxidized glutathione (GSSG), superoxide dismutase (SOD), NF-κB, TNF-α and myeloperoxidase (MPO); (3) Results: HO-1 protein concentration, HO-1 activity, SOD protein concentration and total glutathione significantly decreased in response to ISO treatment. When PAC was administered in conjunction with ISO, HO-1, SOD concentration and total glutathione were not different from control levels. MPO activity, NF-κB concentration and TNF-α protein concentration were significantly increased in the ISO-only group, while the levels of these molecules were restored when PAC was co-administered; (4) Conclusions: Oral administration of PAC can maintain the expression of important antioxidants, anti-inflammatory molecules, HO-1, SOD and GSH, and suppress the production of TNF-α, MPO and NF-κB, which are involved in myocardial damage. The principal component of this cellular defense seems to be the expression of HO-1.
(1) 背景：在心血管应用中，紫杉醇可抑制平滑肌细胞增殖和迁移，并显著降低再狭窄和靶病变血管重建的发生率。然而，紫杉醇在心肌中的细胞效应尚未完全明确；(2) 方法：将Wistar大鼠分为四组：对照组（CTRL）、异丙肾上腺素（ISO）处理组（1 mg/kg）以及两组紫杉醇（PAC）处理组，紫杉醇以10 mg/kg/天的剂量通过灌胃/经口给药，单独给药5天，或在ISO处理3周后联合给药（ISO + PAC）。24小时后采集心室组织，测量血红素加氧酶（HO-1）、还原型谷胱甘肽（GSH）、氧化型谷胱甘肽（GSSG）、超氧化物歧化酶（SOD）、核因子κB（NF-κB）、肿瘤坏死因子-α（TNF-α）和髓过氧化物酶（MPO）；(3) 结果：ISO处理后，HO-1蛋白浓度、HO-1活性、SOD蛋白浓度和总谷胱甘肽显著降低。当PAC与ISO联合给药时，HO-1、SOD浓度和总谷胱甘肽与对照水平无差异。仅ISO组的MPO活性、NF-κB浓度和TNF-α蛋白浓度显著升高，而联合给予PAC时，这些分子的水平恢复正常；(4) 结论：口服PAC可维持重要抗氧化剂、抗炎分子HO-1、SOD和GSH的表达，并抑制参与心肌损伤的TNF-α、MPO和NF-κB的产生。这种细胞防御的主要成分似乎是HO-1的表达。
