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

• Published in: Naunyn-Schmiedeberg's archives of pharmacology Vol. 397; no. 7; pp. 5193 - 5205
• Main Authors: Dawoud, Mohamed, Attallah, Khalid M., Ibrahim, Ismail T., Karam, Heba M., Ibrahim, Ayman A.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.07.2024; Springer Nature B.V
• Subjects: Animals; Antioxidants; Antioxidants - pharmacology; Apoptosis; Apoptosis - drug effects; Apoptosis - radiation effects; Biomedical and Life Sciences; Biomedicine; Caspase-3; Gamma Rays - adverse effects; Glutathione peroxidase; HMGB1 protein; Hyaluronic acid; Hyaluronic Acid - pharmacology; Inflammation; Intestine; Intestines - drug effects; Intestines - pathology; Intestines - radiation effects; Ionizing radiation; Male; Mice; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondria - radiation effects; Nanoparticles; Neurosciences; Organophosphorus Compounds - pharmacology; Oxidative stress; Oxidative Stress - drug effects; Oxidative Stress - radiation effects; Pharmacology/Toxicology; Radiation Injuries, Experimental - drug therapy; Radiation Injuries, Experimental - metabolism; Radiation Injuries, Experimental - pathology; Radiation Injuries, Experimental - prevention & control; Radiation therapy; Radiation-Protective Agents - pharmacology; Radiation-Protective Agents - therapeutic use; Reactive oxygen species; Ubiquinone - analogs & derivatives; Ubiquinone - pharmacology; γ Radiation; Intestinal injury; Gamma radiation; MitoQ; Hyaluronic acid
• ISSN: 0028-1298; 1432-1912; 1432-1912
• DOI: 10.1007/s00210-024-02948-5

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.