Neuroprotective effects of Trimetazidine against Cisplatin‐induced peripheral neuropathy: Involvement of AMPK‐mediated PI3K/mTOR, Nrf2, and NF‐κB signaling axes

authored by: Marawan A. Elbaset, Sherif M. Afifi, Tuba Esatbeyoglu, Sahar S. Abdelrahman, Dalia O. Saleh, Jeannette Vasquez-Vivar
Abstract: Cisplatin-induced peripheral neuropathy (CIPN) is a common and debilitating side effect of cisplatin chemotherapy used in cancer treatment. This study explored the neuroprotective effects of Trimetazidine (TRI) against CIPN by preserving nerve integrity, reducing neuro-oxidative stress, and alleviating neuroinflammation. Using a rat model of CIPN, we evaluated TRI's impact on motor coordination, pain sensitivity, and peripheral nerve histopathology. Also, its effects on neuro-oxidative stress and neuroinflammatory markers were assessed. The findings showed that rats with CIPN had worse motor coordination and increased sensitivity to pain but that these symptoms were alleviated by TRI therapy in a dose-dependent way. Nerve conduction velocities were normalized, and expression of genes involved in neuropathy signaling was suppressed after TRI therapy. Antioxidant benefits were also shown in TRI, with oxidative damage being reduced and the cellular energy balance being restored. By inhibiting the production of inflammatory markers, it also demonstrated anti-inflammatory properties. Histopathological examination revealed that TRI, especially when administered at a higher dose, inhibited the degeneration and demyelination of nerve fibers. The anti-inflammatory properties of TRI in the sciatic nerves were further shown by the fact that its administration reduced iNOS expression. In conclusion, AMPK-mediated PI3K/mTOR, Nrf2, and NF-κB signaling pathways may all be involved in the therapeutic benefits of TRI for CIPN. These results indicate that TRI may be useful for reducing the side effects of CIPN and enhancing patient outcomes during cisplatin chemotherapy.
Organisation(s): Institute of Food Science and Human Nutrition
Molecular Food Chemistry and Food Development
Institute of Food and One Health
External Organisation(s): National Research Centre (NRC)
University of Bologna
Cairo University
Type: Article
Journal: Oxidative Medicine and Cellular Longevity
Volume: 2024
ISSN: 1942-0900
Publication date: 20.08.2024
Publication status: Published
Peer reviewed: Yes
Sustainable Development Goals: SDG 3 - Good Health and Well-being
Electronic version(s): https://doi.org/10.1155/2024/6612009 (Access: Open)

BibTeX

@article{0f36b5f2a4b24a0d8bdab0b46e78b868,
title = "Neuroprotective effects of Trimetazidine against Cisplatin‐induced peripheral neuropathy: Involvement of AMPK‐mediated PI3K/mTOR, Nrf2, and NF‐κB signaling axes",
abstract = "Cisplatin-induced peripheral neuropathy (CIPN) is a common and debilitating side effect of cisplatin chemotherapy used in cancer treatment. This study explored the neuroprotective effects of Trimetazidine (TRI) against CIPN by preserving nerve integrity, reducing neuro-oxidative stress, and alleviating neuroinflammation. Using a rat model of CIPN, we evaluated TRI's impact on motor coordination, pain sensitivity, and peripheral nerve histopathology. Also, its effects on neuro-oxidative stress and neuroinflammatory markers were assessed. The findings showed that rats with CIPN had worse motor coordination and increased sensitivity to pain but that these symptoms were alleviated by TRI therapy in a dose-dependent way. Nerve conduction velocities were normalized, and expression of genes involved in neuropathy signaling was suppressed after TRI therapy. Antioxidant benefits were also shown in TRI, with oxidative damage being reduced and the cellular energy balance being restored. By inhibiting the production of inflammatory markers, it also demonstrated anti-inflammatory properties. Histopathological examination revealed that TRI, especially when administered at a higher dose, inhibited the degeneration and demyelination of nerve fibers. The anti-inflammatory properties of TRI in the sciatic nerves were further shown by the fact that its administration reduced iNOS expression. In conclusion, AMPK-mediated PI3K/mTOR, Nrf2, and NF-κB signaling pathways may all be involved in the therapeutic benefits of TRI for CIPN. These results indicate that TRI may be useful for reducing the side effects of CIPN and enhancing patient outcomes during cisplatin chemotherapy.",
author = "Elbaset, {Marawan A.} and Afifi, {Sherif M.} and Tuba Esatbeyoglu and Abdelrahman, {Sahar S.} and Saleh, {Dalia O.} and Jeannette Vasquez-Vivar",
note = "Publisher Copyright: {\textcopyright} 2024 Marawan A. Elbaset et al.",
year = "2024",
month = aug,
day = "20",
doi = "10.1155/2024/6612009",
language = "English",
volume = "2024",
journal = "Oxidative Medicine and Cellular Longevity",
issn = "1942-0900",
publisher = "Hindawi Publishing Corporation",
}