Angiotensin II Type 1 receptor blockade attenuates the neuropathological changes in the spinal cords of diabetic rats with modulation of nuclear factor erythroid 2-related factor 2/ heme oxygenase 1 system.

Autor: Elsayed HRH; Department of Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura, Egypt; Department of Anatomy and Neurobiology, College of Medicine & Health Sciences, National University of Science and Technology, Sohar, Oman. Electronic address: easy_anatomy@mans.edu.eg., Ali EMT; Department of Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura, Egypt; Department of Anatomy, Faculty of Medicine, Taibah University, Madinah, Saudi Arabia., Rabei MR; Department of Medical Physiology, Faculty of Medicine, Mansoura University, Mansoura, Egypt; Department of Basic Medical Sciences, Faculty of Medicine, Ibn Sina University for Medical Sciences, Amman, Jordan., El Nashar EM; Department of Anatomy, College Medicine, King Khalid University, Abha, Saudi Arabia., Alghamdi MA; Department of Anatomy, College Medicine, King Khalid University, Abha, Saudi Arabia; Genomics and Personalized Medicine Unit, The Center for Medical and Health Research, King Khalid University, Abha, Saudi Arabia., Al-Zahrani NS; Department of Clinical Biochemistry, College of Medicine, King Khalid University, Abha, Saudi Arabia., Alshehri SH; Department of Orthopedics, College of Medicine, King Khalid University, Abha, Saudi Arabia., Aldahhan RA; Department of Anatomy, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia., Morsy AI; Department of Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Jazyk: angličtina
Zdroj: Tissue & cell [Tissue Cell] 2024 Jun; Vol. 88, pp. 102420. Date of Electronic Publication: 2024 May 23.
DOI: 10.1016/j.tice.2024.102420
Abstrakt: Peripheral and central neuropathies frequently complicate worldwide diabetes. Compared to peripheral neuropathy, central neuropathy didn`t gain a major research interest. Angiotensin II is reported to be involved in diabetic neuropathic pain but its role in the central pathological changes in the spinal cord is not clear. Here, we study the role of Losartan; an Angiotensin II receptor 1 (AT1) antagonist in suppression of the diabetes-induced changes in the spinal cord. Three groups of rats were applied; a negative control group, a streptozotocin (STZ) diabetic group, and a group receiving STZ and Losartan. After two months, the pathological alteration in the spinal cord was investigated, and an immunohistochemical study was performed for neuronal, astrocytic, and microglial markers; nuclear protein (NeuN), Glial fibrillary acidic protein (GFAP), and Ionized calcium-binding adaptor molecule 1 (Iba1), respectively, and for an apoptosis marker; caspase-3, and the inflammatory marker; nuclear factor kappa B (NF-kB) signaling, heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2); physiological antioxidant system. The results showed that Losartan caused recovery of spinal cord changes, by inhibiting the microglial and astrocytic activation, suppressing neuronal apoptosis and NF-kB expression with activation of Nrf2/HO-1 (P<0.0005). It is suggested, herein, that Losartan can suppress diabetes-induced glial activation, inflammation, neuronal apoptosis, and oxidative stress in the spinal cord; the mechanisms that may underlie the role of AT1 antagonism in suppressing diabetic neuropathic pain.
Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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