Nrf2/HO-1 Pathway Mediates the Protective Impact of Metrnl on Oxaliplatin-Induced Peripheral Neuropathy in Rats
Khodir, S., El-Haroun, H., Gaafar, A., A. Zayed, M., Rizk, S., lashin, M., S. Mohamed, A., Ahmed, K. (2025). Nrf2/HO-1 Pathway Mediates the Protective Impact of Metrnl on Oxaliplatin-Induced Peripheral Neuropathy in Rats. EKB Journal Management System, 45(1), 1-17. doi: 10.21608/besps.2024.319683.1177
Suzan A Khodir; Hala El-Haroun; Ahmed Mohamed Gaafar; Mohamed A. Zayed; Sara Kamal Rizk; Mohamed Elsaeed lashin; Amira S. Mohamed; Karima El-Sayed Ahmed. "Nrf2/HO-1 Pathway Mediates the Protective Impact of Metrnl on Oxaliplatin-Induced Peripheral Neuropathy in Rats". EKB Journal Management System, 45, 1, 2025, 1-17. doi: 10.21608/besps.2024.319683.1177
Khodir, S., El-Haroun, H., Gaafar, A., A. Zayed, M., Rizk, S., lashin, M., S. Mohamed, A., Ahmed, K. (2025). 'Nrf2/HO-1 Pathway Mediates the Protective Impact of Metrnl on Oxaliplatin-Induced Peripheral Neuropathy in Rats', EKB Journal Management System, 45(1), pp. 1-17. doi: 10.21608/besps.2024.319683.1177
Khodir, S., El-Haroun, H., Gaafar, A., A. Zayed, M., Rizk, S., lashin, M., S. Mohamed, A., Ahmed, K. Nrf2/HO-1 Pathway Mediates the Protective Impact of Metrnl on Oxaliplatin-Induced Peripheral Neuropathy in Rats. EKB Journal Management System, 2025; 45(1): 1-17. doi: 10.21608/besps.2024.319683.1177

Nrf2/HO-1 Pathway Mediates the Protective Impact of Metrnl on Oxaliplatin-Induced Peripheral Neuropathy in Rats

Bulletin of Egyptian Society for Physiological Sciences
Volume 45, Issue 1, January 2025, Page 1-17  XML PDF (1017.6 K)
Document Type: Review Article
DOI: 10.21608/besps.2024.319683.1177
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Authors
Suzan A Khodirorcid 1; Hala El-Harounorcid 2; Ahmed Mohamed Gaafar1; Mohamed A. Zayed1; Sara Kamal Rizk3; Mohamed Elsaeed lashin4; Amira S. Mohamedorcid 5; Karima El-Sayed Ahmed email orcid 6
1Medical Physiology Department, Faculty of Medicine, Menoufia University, Shebin El-Kom, Menoufia, Egypt.
2Histology and Cell Biology Department, Faculty of Medicine, Menoufia University, Shebin El-Kom, Menoufia
3Medical Biochemistry and Molecular Biology Department, Faculty of medicine, Menoufia University, Egypt.
4Neuropsychiatry Department, Faculty of Medicine, Menoufia University.
5Pharmacology Department, Faculty of medicine, Suez Canal University.
6Physiology department, faculty of medicine, Suez canal university
Abstract
Abstract

Introduction: While oxaliplatin (OXL) is an effective cancer chemotherapy, OXL-based therapy's practical usefulness is limited by its adverse effects, which include peripheral neuropathy (PN).Objective: to assess the potential underlying processes and the protective impact of metrnl in PN caused by OXL. Materials and Methods: There were three groups of thirty adult male albino rats: control, OXL and OXL+Metrnl groups (10/group). Electromyography (EMG) and nerve conduction velocity (NCV) were applied to rats, together with behavioral testing for pain and sensory abnormalities. The expression of several genes was evaluated in the sciatic nerve, including tissue MDA, (SOD), TNF-α, interleukin (IL)-6, IL-10, caspase-3, BDNF, nuclear factor E2‐related factor 2 (Nrf2), and homo-oxygenase 1 (HO-1). Additionally, histopathological evaluations of the gastrocnemius and sciatic nerve were carried out.

Results The OXL group exhibited mechanical and cold allodynia, as well as significantly higher levels of MDA, TNF-α, IL-6, and caspase-3 than the control group. It also significantly reduced NCV, EMG recordings, IL-10, as well as down-regulating BDNF, Nrf2 and HO-1 gene expression in the sciatic nerve. OXL-induced PN changes were significantly ameliorated in the OXL+Metrnl groups. Conclusion: Metrnl has valuable protective effects on OXL-induced PN via anti-oxidant, anti-inflammatory, inhibition of apoptosis and neurotrophic effects in addition to up-regulation of Nrf2 and HO-1 gene expressions.
Keywords
BDNF; HO1; Metrnl; Nrf2; Oxaliplatin
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