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Dexpanthenol ameliorates doxorubicin-induced lung injury by regulating endoplasmic reticulum stress and apoptosis

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Abstract

Doxorubicin (DOX), which is used as a chemotherapeutic agent in the treatment of tumors, has limited use due to its toxicity in various organs and tissues. One of the organs where DOX has a toxic effect is the lung. DOX shows this effect by increasing oxidative stress, inflammation, and apoptosis. Dexpanthenol (DEX), a homologue of pantothenic acid, has anti-inflammatory, antioxidant, and anti-apoptotic properties. Therefore, the purpose of our investigation was to explore how DEX could counteract the harmful effects of DOX on the lungs. Thirty-two rats were used in the study, and 4 groups were formed (control, DOX, DOX + DEX, and DEX). In these groups, parameters of inflammation, ER stress, apoptosis, and oxidative stress were evaluated by immunohistochemistry, RT-qPCR, and spectrophotometric methods. In addition, lung tissue was evaluated histopathologically in the groups. While CHOP/GADD153, caspase-12, caspase-9, and Bax gene expressions increased in the DOX group, Bcl-2 gene expression levels significantly decreased. In addition, changes in Bax and Bcl-2 were supported immunohistochemically. There was a significant increase in oxidative stress parameters and a significant decrease in antioxidant levels. In addition, an increase in inflammatory marker (TNF-α and IL-10) levels was determined. There was a decrease in CHOP/GADD153, caspase-12, caspase-9, and Bax gene expressions and an increase in Bcl-2 gene expression in the DEX-treated group. In addition, it was determined that there was a decrease in oxidative stress levels and inflammatory findings. The curative effect of DEX was supported by histopathological findings. As a result, it was experimentally determined that DEX has a healing effect on oxidative stress, ER stress, inflammation, and apoptosis in lung damage caused by DOX toxicity.

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Acknowledgements

We would like to thank Suleyman Demirel University Scientific Research Projects Coordination Unit for their contributions (Project ID: TSG-2022-8783).

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Authors and Affiliations

  1. Department of Medical Genetics, University of Süleyman Demirel, Isparta, 32300, Turkey

    Muhammet Yusuf Tepebaşı

  2. Department of Medical Biochemistry, University of Süleyman Demirel, Isparta, Turkey

    Halil İbrahim Büyükbayram

  3. Department of Pathology, University of Mehmet Akif Ersoy, Burdur, Turkey

    Özlem Özmen & Şerife Taşan

  4. Department of Medical Biology, University of Süleyman Demirel, Isparta, Turkey

    Esma Selçuk

Authors
  1. Muhammet Yusuf Tepebaşı
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  2. Halil İbrahim Büyükbayram
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  3. Özlem Özmen
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  4. Şerife Taşan
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  5. Esma Selçuk
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Contributions

 MYT and ES conducted genetic analysis, prepared the article design, designed figures and tables, and compiled literature resources. HIB made biochemical analyzes and article editing. ÖÖ and ŞT performed histopathological and immunohistochemical experiments and analysis of the results. The authors declare that all data is produced in-house and is paper mill free.

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Correspondence to Muhammet Yusuf Tepebaşı.

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Ethical approval

The experiment was carried out in accordance with the guidelines for the treatment and experimentation of animals provided in the pertinent European Communities Council Directive (86/609/EEC), and it was given the go-ahead by the Suleyman Demirel University Committee on Animal Research (Approval No. 01.26.2023/01-122).

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The authors declare no competing interests.

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Tepebaşı, M.Y., Büyükbayram, H.İ., Özmen, Ö. et al. Dexpanthenol ameliorates doxorubicin-induced lung injury by regulating endoplasmic reticulum stress and apoptosis. Naunyn-Schmiedeberg's Arch Pharmacol 396, 1837–1845 (2023). https://doi.org/10.1007/s00210-023-02497-3

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  • DOI: https://doi.org/10.1007/s00210-023-02497-3

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