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RETRACTED ARTICLE: Simvastatin-loaded nano-niosomes efficiently downregulates the MAPK-NF-κB pathway during the acute phase of myocardial ischemia-reperfusion injury

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This article was retracted on 26 April 2023

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Abstract

Background

Simvastatin can potentially mitigate acute inflammatory phase of myocardial ischemia-reperfusion injury. However, these effects negatively influenced by its poor bioavailability, low water solubility and high metabolism. Here, we investigated the effects of SIM-loaded nano-niosomes on a rat model of MI/R injury to find a drug delivery method to tackle the barriers.

Methods

Nano-niosomes’ characteristics were identified using dynamic light scattering and transmission electron microscopy. Fifty male Wistar rats were divided into five groups: Sham; MI/R; MI/R + nano-niosome; MI/R + SIM; MI/R + SIM-loaded nano-niosomes. Left anterior descending artery was ligated for 45 min, and 3 mg/kg SIM, nano-niosomes, or SIM-loaded nano-niosomes was intramyocardially injected ten min before the onset of reperfusion. ELISA assay was used to assess cardiac injury markers (cTnI, CK-MB) and inflammatory cytokines (TNF-α, IL-6, TGF-β, MPC-1). Expression level of MAPK-NF-κB and histopathological changes were evaluated by western blot and hematoxylin & eosin staining, respectively.

Results

the size of nano-niosome was 137 nm, reached to 163 nm when simvastatin was loaded. To achieve optimized niosomes span 80, a drug/cholesterol ratio of 0.4 and seven min of sonication time was applied. Optimized entrapment efficiency of SIM-loaded nano-niosomes was 98.21%. Inflammatory cytokines and the expression level of MAPK and NF-κB were reduced in rats receiving SIM-loaded nano-niosomes compared to MI/R + SIM and MI/R + SIM-loaded nano-niosomes.

Conclusion

Our results showed that SIM-loaded nano-niosomes could act more efficiently than SIM in alleviating the acute inflammatory response of reperfusion injury via downregulating the activation of MAPK-NF-κB.

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Data Availability

All datasets generated are available on request.

Change history

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Acknowledgements

This study was funded by a research grant from the Physiology Research Center, Iran University of Medical Science, Tehran, Iran.

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The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

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    Authors and Affiliations

    1. Department of Cellular and Molecular Biology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran

      Maryam Naseroleslami

    2. Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran

      Masoomeh Sharifi & Nahid Aboutaleb

    3. Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

      Masoomeh Sharifi & Nahid Aboutaleb

    4. Department of Medical Biotechnology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran

      Neda Mousavi Niri

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    1. Maryam Naseroleslami
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    4. Nahid Aboutaleb
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    Contributions

    The study was designed by [Nahid Aboutaleb]. [Masoomeh Sharifi] and [Maryam Naseroleslami] performed the animal model and experimental study. Data analyses and interpretation were accomplished by [Neda Mousavi Niri]. The first draft of the manuscript was written and proofread by [Nahid Aboutaleb] and [Masoomeh Sharifi]. All authors read and approved the final manuscript.

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    Correspondence to Nahid Aboutaleb.

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    The authors declare no conflict of interest.

    Competing Interests

    The authors have no relevant financial or non-financial interests to disclose.

    Ethics approval

    Guidelines for using animals in this study were approved by the Committee of the Care and Use of Laboratory Animals at Iran University of Medical Sciences, ethical number: IR.IUMS.REC.1398.625. The Committee is credited by the Ministry of Health and Medical Education, which is initially works on the basis of The Declaration of Helsinki, the fifth revision.

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    Maryam Naseroleslami and Masoomeh Sharifi authors have equally contributed to this work.

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    Naseroleslami, M., Sharifi, M., Mousavi Niri, N. et al. RETRACTED ARTICLE: Simvastatin-loaded nano-niosomes efficiently downregulates the MAPK-NF-κB pathway during the acute phase of myocardial ischemia-reperfusion injury. Mol Biol Rep 49, 10377–10385 (2022). https://doi.org/10.1007/s11033-022-07891-3

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