Resolvin E1 protects against doxorubicin-induced cardiotoxicity by inhibiting oxidative stress, autophagy and apoptosis by targeting AKT/mTOR signaling

Zhang, Jishou; Wang, Menglong; Ding, Wen; Zhao, Mengmeng; Ye, Jing; Xu, Yao; Wang, Zhen; Ye, Di; Li, Dan; Liu, Jianfang; Wan, Jun

doi:10.1016/j.bcp.2020.114188

Cited by 50 publications

(25 citation statements)

References 54 publications

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“…By using rapamycin, we verified the discovery that adriamycin can cause heart damage by enhancing autophagy. Previous studies ( Zhang et al, 2020a ) have shown that adriamycin can enhance autophagy through PI3K/Akt/mTOR signaling. The protein level of PI3K in the heart is also related to HF.…”

Section: Discussionmentioning

confidence: 95%

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Astragaloside IV Attenuates the Myocardial Injury Caused by Adriamycin by Inhibiting Autophagy

et al. 2021

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Astragaloside IV (ASIV) is the main active component of Astragalus, and can ameliorate cardiomyocyte hypertrophy, apoptosis and fibrosis. In this experiment, we studied how ASIV reduces the cardiotoxicity caused by adriamycin and protects the heart. To this end, rats were randomly divided into the control, ADR, ADR + ASIV and ASIV groups (n = 6). Echocardiography was used to observe cardiac function, HE staining was used to observe myocardial injury, TUNEL staining was used to observe myocardial cell apoptosis, and immunofluorescence and Western blotting was used to observe relevant proteins expression. Experiments have shown that adriamycin can damage heart function in rats, and increase the cell apoptosis index, autophagy level and oxidative stress level. Further results showed that ADR can inhibit the PI3K/Akt pathway. ASIV treatment can significantly improve the cardiac function of rats treated with ADR and regulate autophagy, oxidative stress and apoptosis. Our findings indicate that ASIV may reduce the heart damage caused by adriamycin by activating the PI3K/Akt pathway.

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Section: Discussionmentioning

confidence: 95%

“…Studies have shown that the cardiotoxicity caused by ADR is mainly related to the oxidative stress caused by ROS ( Khadka et al, 2018 ), which is a complex multifactor process. It has been shown in the literature that the oxidative stress caused by ROS can directly induce autophagy and apoptosis ( Zhang et al, 2020a ).…”

Section: Discussionmentioning

confidence: 99%

Astragaloside IV Attenuates the Myocardial Injury Caused by Adriamycin by Inhibiting Autophagy

et al. 2021

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“…This includes the development of improved dosage forms of DOX itself, as well as the development of agents that mitigate oxidative stress, inflammation, and apoptosis. This leads to biochemical, molecular, structural and histological alterations and appear as common pathogenic events in DOX-induced acute cardiotoxicity [ 5 , 6 ]. Numerous antioxidants, anti-inflammatory and antiapoptotic agents of natural and synthetic origins, have been shown to exert protective effects in preclinical models of DOX-induced cardiotoxicity.…”

Section: Introductionmentioning

confidence: 99%

Nerolidol Attenuates Oxidative Stress, Inflammation, and Apoptosis by Modulating Nrf2/MAPK Signaling Pathways in Doxorubicin-Induced Acute Cardiotoxicity in Rats

et al. 2021

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The clinical usage of doxorubicin (DOX), a potent anthracycline antineoplastic drug, is often limited by its cardiotoxic effects. Thus, for improving usage of DOX, the aim of this study was to assess the cardioprotective effects of nerolidol (NERO) in a rat model of DOX-induced acute cardiotoxicity and examine underlying molecular mechanisms that contribute to these effects. To induce acute cardiotoxicity male albino Wistar rats were injected with single dose intraperitoneal DOX (12.5 mg/kg). The rats were treated with NERO (50 mg/kg, orally) for five days. DOX-injected rats showed elevated levels of cardiac marker enzymes and enhanced oxidative stress markers along with altered Nrf2/Keap1/HO-1 signaling pathways. DOX administration also induced the activation of NF-κB/MAPK signaling and increased the levels and expression of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) as well as expression of inflammatory mediators (iNOS and COX-2) in the heart. DOX also triggered DNA damage and apoptotic cell death in the myocardium. Additionally, histological studies revealed structural alterations of the myocardium. NERO treatment exhibited protection against the deleterious results of DOX on myocardium, as evidenced by the restoration of altered biochemical parameters, mitigated oxidative stress, inflammation, and apoptosis. The findings of the present study demonstrate that NERO provides cardioprotective effects against DOX-induced acute cardiotoxicity attributed to its potent antioxidant, anti-inflammatory, and antiapoptotic activities through modulating cellular signaling pathways.

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“…Mice were randomly assigned into four groups as control+vehicle, control+OA, DOX+vehicle, and DOX+OA ( n = 10 per group). The mice in our study were intraperitoneally injected with DOX at a dose of 20 mg/kg to establish the model of DOX-related cardiac injury [ 17 ]. To evaluate the effects of OA on DOX-induced acute cardiotoxicity, mice were orally given OA (40 mg/kg) or the same volume of CMC-Na solution for ten days beginning from five days before DOX injection.…”

Section: Methodsmentioning

confidence: 99%

Protective Effects of Oroxylin A against Doxorubicin‐Induced Cardiotoxicity via the Activation of Sirt1 in Mice

Zhang

Yang

2021

Oxidative Medicine and Cellular Longevity

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Doxorubicin- (DOX-) related cardiac injury impairs the life quality of patients with cancer. This largely limited the clinical use of DOX. It is of great significance to find a novel strategy to reduce DOX-related cardiac injury. Oroxylin A (OA) has been identified to exert beneficial effects against inflammatory diseases and cancers. Here, we investigated whether OA could attenuate DOX-induced acute cardiotoxicity in mice. A single dose of DOX was used to induce acute cardiac injury in mice. To explore the protective effects, OA was administered to mice for ten days beginning from five days before DOX injection. The data in our study indicated that OA inhibited DOX-induced heart weight loss, reduction in cardiac function, and the elevation in myocardial injury markers. DOX injection resulted in increased oxidative damage, inflammation accumulation, and myocardial apoptosis in vivo and in vitro, and these pathological alterations were alleviated by treatment of OA. OA activated the sirtuin 1 (Sirt1) signaling pathway via the cAMP/protein kinase A, and its protective effects were blocked by Sirt1 deficiency. OA treatment did not affect the tumor-killing action of DOX in tumor-bearing mice. In conclusion, OA protected against DOX-related acute cardiac injury via the regulation of Sirt1.

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Resolvin E1 protects against doxorubicin-induced cardiotoxicity by inhibiting oxidative stress, autophagy and apoptosis by targeting AKT/mTOR signaling

Cited by 50 publications

References 54 publications

Astragaloside IV Attenuates the Myocardial Injury Caused by Adriamycin by Inhibiting Autophagy

Astragaloside IV Attenuates the Myocardial Injury Caused by Adriamycin by Inhibiting Autophagy

Nerolidol Attenuates Oxidative Stress, Inflammation, and Apoptosis by Modulating Nrf2/MAPK Signaling Pathways in Doxorubicin-Induced Acute Cardiotoxicity in Rats

Protective Effects of Oroxylin A against Doxorubicin‐Induced Cardiotoxicity via the Activation of Sirt1 in Mice

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