Neuroprotective Effects of Trimetazidine against Cisplatin-Induced Peripheral Neuropathy: Involvement of AMPK-Mediated PI3K/mTOR, Nrf2, and NF-κB Signaling Axes.
2区 生物学Q1 Biochemistry, Genetics and Molecular Biology
Marawan A Elbaset, Sherif M Afifi, Tuba Esatbeyoglu, Sahar S Abdelrahman, Dalia O Saleh
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引用次数: 0
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.
期刊介绍:
Oxidative Medicine and Cellular Longevity is a unique peer-reviewed, Open Access journal that publishes original research and review articles dealing with the cellular and molecular mechanisms of oxidative stress in the nervous system and related organ systems in relation to aging, immune function, vascular biology, metabolism, cellular survival and cellular longevity. Oxidative stress impacts almost all acute and chronic progressive disorders and on a cellular basis is intimately linked to aging, cardiovascular disease, cancer, immune function, metabolism and neurodegeneration. The journal fills a significant void in today’s scientific literature and serves as an international forum for the scientific community worldwide to translate pioneering “bench to bedside” research into clinical strategies.