Benazepril hydrochloride protects against doxorubicin cardiotoxicity by regulating the PI3K/Akt pathway.
Benazepril hydrochloride protects against doxorubicin cardiotoxicity by regulating the PI3K/Akt pathway.
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盐酸贝那普利通过调节 PI3K/Akt 通路预防阿霉素心脏毒性
DOI：
10.3892/etm.2021.10516
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发表时间：
2021-10
影响因子：
2.7
通讯作者：
Wu S
中科院分区：
文献类型：
--
作者：
Zhan L;Wang X;Zhang Y;Zhu G;Ding Y;Chen X;Jiang W;Wu S
阿霉素（DOX）刺激活性氧的产生，从而损害线粒体功能。血管紧张素转换酶抑制剂（ACEI）已被确定为表现出对心血管疾病的保护作用。本研究旨在验证ACEI盐酸苯那普利（HCl）可以保护DOX诱导的心脏毒性的假设。采用体外培养的大鼠胚胎心肌成肌细胞系H9 c2细胞建立DOX损伤模型。用盐酸苯那普利、DOX或DOX与盐酸苯那普利的混合物处理H9 c2细胞，以测定心肌酶包括乳酸脱氢酶（LDH）、超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶的活性以及培养液中丙二醛的浓度。未进行任何处理的细胞用作对照。与未处理的对照细胞相比，DOX处理的H9 c2细胞的心肌酶活性水平增加。此外，与盐酸苯那普利的共同治疗显著降低了由于DOX介导的细胞损伤而发生的细胞凋亡水平。机制实验表明，盐酸苯那普利预处理可通过PI 3 K/Akt信号通路对抗DOX诱导的氧化应激，抑制细胞凋亡。相比之下，Akt抑制剂（MK 2206）抑制盐酸苯那普利对DOX诱导的H9 c2细胞损伤的保护作用，如H9 c2细胞中LDH释放增加所揭示的。这些结果表明，盐酸苯那普利可能作为DOX的佐剂在长期临床使用中给药。
Doxorubicin (DOX) stimulates the generation of reactive oxygen species, thereby impairing mitochondrial functions. Angiotensin-converting enzyme inhibitors (ACEIs) have been identified to exhibit protective effects on cardiovascular diseases. The present study aimed to test the hypothesis that an ACEI benazepril hydrochloride (HCl) may protect against DOX-induced cardiotoxicity. The DOX injury model was established using rat embryonic cardiac myoblast cells (H9c2 cell line) treated with DOX in vitro. H9c2 cells were treated with benazepril-HCl, DOX or a mixture of DOX and benazepril-HCl to measure the activities of myocardial enzymes including lactate dehydrogenase (LDH), superoxide dismutase, catalase and glutathione peroxidase, in addition to the concentration of malondialdehyde in the culture medium. Cells without any treatment were used as a control. DOX treatment increased the levels of activity of myocardial enzymes in H9c2 cells compared with those in the untreated control cells. Additionally, co-treatment with benazepril-HCl significantly reduced the levels of apoptosis occurring due to DOX-mediated cellular damage. The mechanistic experiment revealed that pretreatment with benazepril-HCl counteracted the DOX-induced oxidative stress and suppressed the activation of apoptosis via the PI3K/Akt signaling pathway. By contrast, an Akt inhibitor (MK2206) inhibited the protective effects of benazepril-HCl against DOX-induced H9c2 cell injury, as revealed by increased LDH release in H9c2 cells. These results suggested that benazepril-HCl may potentially be administered as an adjuvant for DOX in long-term clinical use.
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影响因子：
2.6
作者：
King JN;Font A;Rousselot JF;Ash RA;Bonfanti U;Brovida C;Crowe ID;Lanore D;Pechereau D;Seewald W;Strehlau G
通讯作者：
Strehlau G
影响因子：
5.6
作者：
Muñoz-Durango N;Fuentes CA;Castillo AE;González-Gómez LM;Vecchiola A;Fardella CE;Kalergis AM
通讯作者：
Kalergis AM
评估爆发骨折中氧化应激水平和抗氧化剂活性。
DOI：
10.12659/msm.908312
发表时间：
2018-01-11
期刊：
Medical science monitor : international medical journal of experimental and clinical research
影响因子：
--
作者：
Kuyumcu F;Aycan A
通讯作者：
Aycan A
影响因子：
3.9
作者：
Gujral, Dorothy M.;Lloyd, Guy;Bhattacharyya, Sanjeev
通讯作者：
Bhattacharyya, Sanjeev
影响因子：
3.5
作者：
Haybar, Habib;Shahrabi, Saeid;Pezeshki, SeyedmohammadSadegh
通讯作者：
Pezeshki, SeyedmohammadSadegh