Crocetin alleviates myocardial ischemia/reperfusion injury by regulating inflammation and the unfolded protein response

Yang, Ming; Mao, Genxiang; Ouyang, Lili; Shi, Chenhui; Hu, Pengfei; Huang, Shouqiang

doi:10.3892/mmr.2019.10891

Cited by 15 publications

(17 citation statements)

References 28 publications

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“…crT significantly decreases lPo, enhances glutathione peroxidase (GSH-Px) and Sod activity and improves the histopathology of the myocardium in hypertrophic tissue (32). Moreover, crT regulates myocardial enzymes to reduce cardiac cytotoxicity and apoptosis levels (32,40). However, it is yet to be elucidated whether crT attenuates aTo-induced cardiotoxicity and reduces arsenic accumulation.…”

Section: Ameliorative Effects and Mechanism Of Crocetin In Arsenic Trmentioning

confidence: 99%

Ameliorative effects and mechanism of crocetin in arsenic trioxide‑induced cardiotoxicity in rats

Zhao

Zheng

et al. 2020

Mol Med Rep

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arsenic trioxide (aTo) is commonly used to treat patients with acute promyelocytic leukemia since it was authorized by the u.S. Food and drug administration in the 1970s, but its applicability has been limited by its cardiotoxic effects. Therefore, the aim of the present study was to investigate the cardioprotective effects and underlying mechanism of crocetin (crT), the critical ingredient of saffron. Sprague-dawley rats were then randomly divided into four groups (n=10/group): i) control group; ii) aTo group, iii) crT-low (20 mg/kg) group; and iv) crT-high (40 mg/kg) group. rats in the control and aTo groups were intraperitoneally injected with equal volumes of 0.9% sodium chloride solution, and crT groups were administered with either 20 and 40 mg/kg crT. Following 6 h, all groups except the control group were intraperitoneally injected with 5 mg/kg aTo over 10 days. cardiotoxicity was indicated by changes in electrocardiographic (ecG) patterns, morphology and marker enzymes. Histomorphological changes in the heart tissue were observed by pathological staining. The levels of superoxide dismutase, glutathione peroxidase, malondialdehyde and catalase in the serum were analyzed using colometric commercial assay kits, and the levels of reactive oxygen species in the heart tissue were detected using the fluorescent probe dihydroethidium. The expression levels of inflammatory factors and activities of apoptosis-related proteins were analyzed using immunohistochemistry. The protein expression levels of silent information regulator of transcription 1 were measured using western blotting. cardiotoxicity was induced in male Sprague-dawley rats with aTo (5 mg/kg). crT (20 and 40 mg/kg) and aTo were co-administered to evaluate possible cardioprotective effects. CRT significantly reduced the heart rate and J-point elevation induced by aTo in rats. Histological changes were evaluated via hematoxylin and eosin staining. crT decreased the levels of creatine kinase and lactate dehydrogenase, increased the activities of superoxide dismutase, glutathione-peroxidase and catalase, and decreased the levels of malondialdehyde and reactive oxygen species. Moreover, crT downregulated the expression levels of the pro-inflammatory factors IL-1, TnF-α, il-6, Bax and p65, as well as increased the expression of Bcl-2. It was also identified that CRT enhanced silent information regulator of transcription 1 protein expression. Thus, the present study demonstrated that crT treatment effectively ameliorated aTo-induced cardiotoxicity. The protective effects of crT can be attributed to the inhibition of oxidative stress, inflammation and apoptosis. Therefore, CRT represents a promising therapeutic method for improving the cardiotoxic side effects caused by aTo treatment, and additional clinical applications are possible, but warrant further investigation.

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Section: Ameliorative Effects and Mechanism Of Crocetin In Arsenic Trmentioning

confidence: 99%

Ameliorative effects and mechanism of crocetin in arsenic trioxide‑induced cardiotoxicity in rats

Zhao

Zheng

et al. 2020

Mol Med Rep

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“…MI/R can cause severe acute inflammation ( Liu et al, 2019 ; Lu et al, 2019 ; Yang et al, 2020 ). Specifically, during MI/R, with the reflow of oxygen and blood, the heart produces a large number of stress reactions.…”

Section: Introductionmentioning

confidence: 99%

Panax quinquefolius L. Saponins Protect Myocardial Ischemia Reperfusion No-Reflow Through Inhibiting the Activation of NLRP3 Inflammasome via TLR4/MyD88/NF-κB Signaling Pathway

et al. 2021

Front. Pharmacol.

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At present, many patients who undergo reperfusion immediately after percutaneous coronary intervention will undergo microvascular obstruction and reduction in myocardial blood flow. This phenomenon is called “no-reflow (NR),” and there is still no effective therapy for NR. Studies showed Panax quinquefolius L. saponins (PQS) have effect on MI/R injury, while the effect and mechanism of PQS on MI/R induced NR are not clear. In this study, we established a MI/R model to investigate whether PQS decrease NR phenomenon via suppression of inflammation. We found that PQS significantly alleviated the symptoms of NR by reducing ischemia, infarction, and NR area; improving cardiac function; preventing pathological morphology changes of myocardium; depressing leukocytes’ aggregation and adhesion; and suppressing the excessive inflammation. Further study demonstrated that PQS remarkably inhibited TLR4, MyD88, p-NF-κB, and NLRP3 inflammasome-associated protein, and these effects could be reversed by LPS. These results indicated that PQS may protect NR by inhibiting the activation of NLRP3 inflammasome via TLR4/MyD88/NF-κB signaling pathway in part, suggesting that PQS exist potential in preventing NR induced by MI/R.

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“…Furthermore, atorvastatin, one of the most frequently used lipid-lowering drugs, statins, was shown to attenuate I/R-induced oxidative stress and inflammation in rat hearts via the Nrf2/HO-1 pathway, resulting in limitation of infarct size [ 101 ]. Recent studies documented that activation of HO-1 is associated with cardioprotection afforded by α 2 -adrenoceptor agonist dexmedetomidine [ 102 ], as well as by a natural compound, crocetin [ 103 ], or hydrogen-rich water [ 104 ]. Finally, an important role of HO-1 in cardioprotection against I/R injury was confirmed in HO-1 knock-out mouse hearts subjected to ex vivo I/R.…”

Section: Heme Oxygenase System In I/r Injury and Cytoprotectionmentioning

confidence: 99%

The Molecular Mechanisms of Iron Metabolism and Its Role in Cardiac Dysfunction and Cardioprotection

Ravingerová

Kindernay

Barteková

et al. 2020

IJMS

106

105

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Iron is an essential mineral participating in different functions of the organism under physiological conditions. Numerous biological processes, such as oxygen and lipid metabolism, protein production, cellular respiration, and DNA synthesis, require the presence of iron, and mitochondria play an important role in the processes of iron metabolism. In addition to its physiological role, iron may be also involved in the adaptive processes of myocardial “conditioning”. On the other hand, disorders of iron metabolism are involved in the pathological mechanisms of the most common human diseases and include a wide range of them, such as type 2 diabetes, obesity, and non-alcoholic fatty liver disease, and accelerate the development of atherosclerosis. Furthermore, iron also exerts potentially deleterious effects that may be manifested under conditions of ischemia/reperfusion (I/R) injury, myocardial infarction, heart failure, coronary artery angioplasty, or heart transplantation, due to its involvement in reactive oxygen species (ROS) production. Moreover, iron has been recently described to participate in the mechanisms of iron-dependent cell death defined as “ferroptosis”. Ferroptosis is a form of regulated cell death that is distinct from apoptosis, necroptosis, and other types of cell death. Ferroptosis has been shown to be associated with I/R injury and several other cardiac diseases as a significant form of cell death in cardiomyocytes. In this review, we will discuss the role of iron in cardiovascular diseases, especially in myocardial I/R injury, and protective mechanisms stimulated by different forms of “conditioning” with a special emphasis on the novel targets for cardioprotection.

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Crocetin alleviates myocardial ischemia/reperfusion injury by regulating inflammation and the unfolded protein response

Cited by 15 publications

References 28 publications

Ameliorative effects and mechanism of crocetin in arsenic trioxide‑induced cardiotoxicity in rats

Ameliorative effects and mechanism of crocetin in arsenic trioxide‑induced cardiotoxicity in rats

Panax quinquefolius L. Saponins Protect Myocardial Ischemia Reperfusion No-Reflow Through Inhibiting the Activation of NLRP3 Inflammasome via TLR4/MyD88/NF-κB Signaling Pathway

The Molecular Mechanisms of Iron Metabolism and Its Role in Cardiac Dysfunction and Cardioprotection

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