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

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 sp...

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Published in:Tissue & cell 2024-06, Vol.88, p.102420, Article 102420
Main Authors: Elsayed, Hassan Reda Hassan, Ali, Eyad Mohamed Tolba, Rabei, Mohammed Rami, El Nashar, Eman Mohamad, Alghamdi, Mansour Abdullah, Al-Zahrani, Norah Saeed, Alshehri, Shaker Hassan, Aldahhan, Rashid A., Morsy, Amira Ibrahim
Format: Article
Language:English
Subjects:
Angiotensin
Astrocytes
Diabetic neuropathy
HO-1
Losartan
Microglia
Neuronal apoptosis
NF-kB
Nrf2
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Summary: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
ISSN:0040-8166
1532-3072
1532-3072
DOI:10.1016/j.tice.2024.102420