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MitoQ and its hyaluronic acid–based nanopreparation mitigating gamma radiation–induced intestinal injury in mice: alleviation of oxidative stress and apoptosis

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Abstract

Perturbations produced by ionizing radiation on intestinal tissue are considered one of highly drastic challenges in radiotherapy. Animals were randomized into five groups. The first group was allocated as control, and the second was subjected to whole body γ-irradiation (10 Gy). The third was administered HA NP (17.6 mg/kg/day; i.p.) and then irradiated. The fourth one received MitoQ (2 mg/kg/day; i.p.) and then irradiated. The last group received MitoQ/HA NP (2 mg/kg/day; i.p.) for 5 days prior to irradiation. Mice were sacrificed a week post-γ-irradiation for evaluation. MitoQ/HA NP ameliorated mitochondrial oxidative stress as indicated by rising (TAC) and glutathione peroxidase and decreasing malondialdehyde, showing its distinguished antioxidant yield. That impacted the attenuation of apoptosis, which was revealed by the restoration of the anti-apoptotic marker and lessening proapoptotic caspase-3. Inflammatory parameters dwindled via treatment with MitoQ/HA NP. Moreover, this new NP exerts its therapeutic action through a distinguished radioprotective pathway (Hmgb1/TLR-4.) Subsequently, these antioxidants and their nanoparticles conferred protection to intestinal tissue as manifested by histopathological examination. These findings would be associated with its eminent antioxidant potential through high mitochondria targeting, enhanced cellular uptake, and ROS scavenging. This research underlines MitoQ/HA NP as a new treatment for the modulation of intestinal damage caused by radiotherapy modalities.

Graphical Abstract

This illustrates that gamma radiation–induced intestinal injury in mice is indicated by an increase in mitochondrial oxidative stress, reactive oxygen species, and intestinal inflammation. The apoptosis marker was increased after irradiation that leads to intestinal damage through the TLR-4 and Hmgb-1 pathways. MitoQ and its hyaluronic acid–based nanopreparation improve all previously mentioned parameters.

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Acknowledgements

We thank Prof. Ahmed Osman, Professor of Pathology at the Faculty of Veterinary Medicine, Cairo University, Egypt, for carrying out the histological examination.

Funding

The authors would like to thank the Deanship of Scientific Research at Umm Al-Qura University, Makkah, Saudi Arabia, for supporting this work by grant code 19-MED-1–01-0038.

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Authors and Affiliations

  1. Department of Pharmaceutics, Faculty of Pharmacy, Helwan University, Cairo, Egypt

    Mohamed Dawoud

  2. Department of Pharmaceutics, Faculty of Pharmacy, Umm Al-Qura, University, Makkah, Saudi Arabia

    Mohamed Dawoud

  3. Labeled Compounds Department, Hot Laboratories Centre, Egyptian Atomic Energy Authority, Cairo, Egypt

    Khalid M. Attallah & Ismail T. Ibrahim

  4. Drug Radiation Research Department, National Center for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority, Cairo, Egypt

    Heba M. Karam & Ayman A. Ibrahim

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  1. Mohamed Dawoud
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  4. Heba M. Karam
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Heba M. Karam and Ayman A. Ibrahim. The first draft of the manuscript was written by Ayman A. Ibrahim. All authors read and approved the final manuscript. The authors declare that all data were generated in-house and that no paper mill was used.

Corresponding author

Correspondence to Heba M. Karam.

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Competing interests

The authors declare no competing interests.

Ethical approval

All animals’ procedures were approved by the Animal Care Committee of the National Centre for Radiation Research and Technology (NCRRT), Cairo, Egypt, which complies with the Guide for Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH Publication No. 85–23, revised 2011).

Rats were obtained from the animal house belonging to the National Center for Radiation Research and Technology (NCRRT), Cairo, Egypt. Mice were maintained in colony cages at 25˚C ± 5˚C, a humidity of 60 ± 5% and housed in suitable illumination conditions (12 h/ 12 h light/dark cycle) and were fed standard pellet diet and fresh water ad libitum. Animals were left one week for acclimatization in the lab environment before starting the experiment. Animals were treated gently; pressure, squeezing, and tough maneuvers were avoided.

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Study highlights

• MitoQ is a potent antioxidant and ameliorates γ-radiation-induced intestinal injury.

• MitoQ/HA NP mitigated intestinal damage produced by γ-irradiation.

• MitoQ/HA NP reduced radiation-induced intestinal oxidative stress and apoptosis.

• MitoQ/HA NP attenuated radiation-induced inflammation in the intestine and Hmgb1/TLR4.

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Dawoud, M., Attallah, K.M., Ibrahim, I.T. et al. MitoQ and its hyaluronic acid–based nanopreparation mitigating gamma radiation–induced intestinal injury in mice: alleviation of oxidative stress and apoptosis. Naunyn-Schmiedeberg's Arch Pharmacol (2024). https://doi.org/10.1007/s00210-024-02948-5

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