Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Institutskaya 3, 142290 Pushchino, Russia.
Prokhorov General Physics Institute of the Russian Academy of Sciences, Vavilov St. 38, 119991 Moscow, Russia.
Int J Mol Sci. 2024 Oct 29;25(21):11596. doi: 10.3390/ijms252111596.
Mitochondrial damage and associated oxidative stress are considered to be major contributory factors in cardiac pathology. One of the most potent naturally occurring antioxidants is taxifolin, especially in its water-soluble form. Herein, the effect of a 14-day course of the peroral application of the water-soluble taxifolin (aqTAX, 15 mg/kg of body weight) on the progression of ultrastructural and functional disorders in mitochondria and the heart's electrical activity in a rat model of myocardial injury induced with isoprenaline (ISO, 150 mg/kg/day for two consecutive days, ) was studied. The delayed ISO-induced myocardial damage was accompanied by an increase in the duration of RR and QT intervals, and long-term application of aqTAX partially restored the disturbed intraventricular conduction. It was shown that the injections of ISO lead to profound ultrastructural alterations of myofibrils and mitochondria in cardiomyocytes in the left ventricle myocardium, including the impairment of the ordered arrangement of mitochondria between myofibrils as well as a decrease in the size and the number of these organelles per unit area. In addition, a reduction in the protein level of the subunits of the respiratory chain complexes I-V and the activity of the antioxidant enzymes catalase, glutathione peroxidase, and Mn-SOD in mitochondria was observed. The application of aqTAX caused an increase in the efficiency of oxidation phosphorylation and a partial restoration of the morphometric parameters of mitochondria in the heart tissue of animals with the experimental pathology. These beneficial effects of aqTAX are associated with the inhibition of lipid peroxidation and the normalization of the enzymatic activities of glutathione peroxidase and Mn-SOD in rat cardiac mitochondria, which may reduce the oxidative damage to the organelles. Taken together, these data allow one to consider this compound as a promising cardioprotector in the complex therapy of heart failure.
线粒体损伤和相关的氧化应激被认为是心脏病理学的主要致病因素。一种最有效的天然抗氧化剂是紫杉叶素，尤其是其水溶性形式。在此，研究了为期 14 天的口服应用水溶性紫杉叶素（aqTAX，15mg/kg 体重）对异丙肾上腺素（ISO，连续两天每天 150mg/kg）诱导的大鼠心肌损伤模型中线粒体超微结构和功能障碍以及心脏电活动进展的影响。延迟的 ISO 诱导的心肌损伤伴随着 RR 和 QT 间期的延长，长期应用 aqTAX 部分恢复了室内传导的紊乱。结果表明，ISO 的注射导致左心室心肌细胞肌原纤维和线粒体的超微结构发生深刻变化，包括线粒体在肌原纤维之间排列有序的破坏，以及这些细胞器的大小和数量每单位面积减少。此外，还观察到呼吸链复合物 I-V 的亚基蛋白水平和线粒体中过氧化氢酶、谷胱甘肽过氧化物酶和 Mn-SOD 的活性降低。aqTAX 的应用导致氧化磷酸化效率的提高，并部分恢复了实验病理学动物心脏组织中线粒体的形态计量参数。aqTAX 的这些有益作用与抑制脂质过氧化和谷胱甘肽过氧化物酶和 Mn-SOD 的酶活性在大鼠心脏线粒体中的正常化有关，这可能减少对细胞器的氧化损伤。总之，这些数据使人们可以将这种化合物视为心力衰竭综合治疗中很有前途的心脏保护剂。
