Tempol improves optic nerve histopathology and ultrastructures in cisplatin-induced optic neuropathy in rats by targeting oxidative stress—Endoplasmic reticulum stress—Autophagy signaling pathways

IntroductionOptic neuropathy is an affection of the optic neurons, which ends with blindness and occurs either primarily due to direct affection of the optic nerve or secondarily as a complication of chronic diseases and/or adverse effects of their therapy. The search for novel therapeutic tools is...

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Main Authors: Amira Ebrahim Alsemeh, Mohey A. E. Hulail, Hanan E. L. Mokhtar, Reham Talaat Eldemerdash, Ioan Banatean-Dunea, Liana Mihaela Fericean, Maha Abdelhamid Fathy, Ahmed Hamed Arisha, Tarek Khamis
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-10-01
Series:Frontiers in Cellular Neuroscience
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Online Access:https://www.frontiersin.org/articles/10.3389/fncel.2023.1256299/full
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author Amira Ebrahim Alsemeh
Mohey A. E. Hulail
Hanan E. L. Mokhtar
Reham Talaat Eldemerdash
Ioan Banatean-Dunea
Liana Mihaela Fericean
Maha Abdelhamid Fathy
Ahmed Hamed Arisha
Ahmed Hamed Arisha
Tarek Khamis
Tarek Khamis
author_facet Amira Ebrahim Alsemeh
Mohey A. E. Hulail
Hanan E. L. Mokhtar
Reham Talaat Eldemerdash
Ioan Banatean-Dunea
Liana Mihaela Fericean
Maha Abdelhamid Fathy
Ahmed Hamed Arisha
Ahmed Hamed Arisha
Tarek Khamis
Tarek Khamis
author_sort Amira Ebrahim Alsemeh
collection DOAJ
description IntroductionOptic neuropathy is an affection of the optic neurons, which ends with blindness and occurs either primarily due to direct affection of the optic nerve or secondarily as a complication of chronic diseases and/or adverse effects of their therapy. The search for novel therapeutic tools is crucial in addressing the limited therapeutic approaches for optic neuropathy. Therefore, the present study was developed to investigate the possible ameliorative effect of tempol against cisplatin-induced optic neuropathy and its underlying mechanism.MethodsForty-eight adult male albino Wistar rats were divided into four equal groups—control, tempol (TEM), cisplatin (CIS), and tempol and cisplatin combined (TEM+CIS). Optic nerve oxidative stress (MDA, SOD, and GPx), gene expression of endoplasmic reticulum stress (ATF-6, XBP-1, BIP, CHOP, and JNK), autophagy 6 (LC3, Beclin-1, and p62) markers, nerve growth factor-1, immunohistochemical expression of (LC3 and p62), histopathological, and electron microscopic examination were performed.ResultsHistopathological and ultrastructure examination validated that cisplatin caused optic neuropathy by inducing oxidative stress, upregulating ER stress markers, and downregulating autophagy markers, and NGF-1 expression. TEM + CIS showed improvement in optic nerve structure and ultrastructure along with oxidative stress, ER stress mRNA, autophagy (immunohistochemical proteins and mRNA) markers, and nerve growth factor mRNA expression.ConclusionsBased on previous findings, tempol represents a valid aid in cisplatin-induced optic neuropathy by implicating new molecular drug targets (ER stress and autophagy) for optic neuropathy therapy.
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spelling doaj.art-6fb02d6ed6154524858568dadda33b102023-10-05T11:49:53ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022023-10-011710.3389/fncel.2023.12562991256299Tempol improves optic nerve histopathology and ultrastructures in cisplatin-induced optic neuropathy in rats by targeting oxidative stress—Endoplasmic reticulum stress—Autophagy signaling pathwaysAmira Ebrahim Alsemeh0Mohey A. E. Hulail1Hanan E. L. Mokhtar2Reham Talaat Eldemerdash3Ioan Banatean-Dunea4Liana Mihaela Fericean5Maha Abdelhamid Fathy6Ahmed Hamed Arisha7Ahmed Hamed Arisha8Tarek Khamis9Tarek Khamis10Human Anatomy and Embryology Department, Faculty of Medicine, Zagazig University Egypt, Zagazig, EgyptHuman Anatomy and Embryology Department, Faculty of Medicine, Zagazig University Egypt, Zagazig, EgyptHuman Anatomy and Embryology Department, Faculty of Medicine, Zagazig University Egypt, Zagazig, EgyptHuman Anatomy and Embryology Department, Faculty of Medicine, Zagazig University Egypt, Zagazig, EgyptDepartment of Biology, Faculty of Agriculture, University of Life Sciences, King Mihai I” from Timisoara [ULST], Timisoara, RomaniaDepartment of Biology, Faculty of Agriculture, University of Life Sciences, King Mihai I” from Timisoara [ULST], Timisoara, RomaniaMedical Physiology Department, Faculty of Medicine, Zagazig University, Zagazig, EgyptDepartment of Animal Physiology and Biochemistry, Faculty of Veterinary Medicine, Badr University in Cairo, Badr City, EgyptDepartment of Physiology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, EgyptDepartment of Pharmacology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, EgyptLaboratory of Biotechnology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, EgyptIntroductionOptic neuropathy is an affection of the optic neurons, which ends with blindness and occurs either primarily due to direct affection of the optic nerve or secondarily as a complication of chronic diseases and/or adverse effects of their therapy. The search for novel therapeutic tools is crucial in addressing the limited therapeutic approaches for optic neuropathy. Therefore, the present study was developed to investigate the possible ameliorative effect of tempol against cisplatin-induced optic neuropathy and its underlying mechanism.MethodsForty-eight adult male albino Wistar rats were divided into four equal groups—control, tempol (TEM), cisplatin (CIS), and tempol and cisplatin combined (TEM+CIS). Optic nerve oxidative stress (MDA, SOD, and GPx), gene expression of endoplasmic reticulum stress (ATF-6, XBP-1, BIP, CHOP, and JNK), autophagy 6 (LC3, Beclin-1, and p62) markers, nerve growth factor-1, immunohistochemical expression of (LC3 and p62), histopathological, and electron microscopic examination were performed.ResultsHistopathological and ultrastructure examination validated that cisplatin caused optic neuropathy by inducing oxidative stress, upregulating ER stress markers, and downregulating autophagy markers, and NGF-1 expression. TEM + CIS showed improvement in optic nerve structure and ultrastructure along with oxidative stress, ER stress mRNA, autophagy (immunohistochemical proteins and mRNA) markers, and nerve growth factor mRNA expression.ConclusionsBased on previous findings, tempol represents a valid aid in cisplatin-induced optic neuropathy by implicating new molecular drug targets (ER stress and autophagy) for optic neuropathy therapy.https://www.frontiersin.org/articles/10.3389/fncel.2023.1256299/fulloptic neuropathyautophagyendoplasmic reticulum stresstempolcisplatin (Cis)
spellingShingle Amira Ebrahim Alsemeh
Mohey A. E. Hulail
Hanan E. L. Mokhtar
Reham Talaat Eldemerdash
Ioan Banatean-Dunea
Liana Mihaela Fericean
Maha Abdelhamid Fathy
Ahmed Hamed Arisha
Ahmed Hamed Arisha
Tarek Khamis
Tarek Khamis
Tempol improves optic nerve histopathology and ultrastructures in cisplatin-induced optic neuropathy in rats by targeting oxidative stress—Endoplasmic reticulum stress—Autophagy signaling pathways
Frontiers in Cellular Neuroscience
optic neuropathy
autophagy
endoplasmic reticulum stress
tempol
cisplatin (Cis)
title Tempol improves optic nerve histopathology and ultrastructures in cisplatin-induced optic neuropathy in rats by targeting oxidative stress—Endoplasmic reticulum stress—Autophagy signaling pathways
title_full Tempol improves optic nerve histopathology and ultrastructures in cisplatin-induced optic neuropathy in rats by targeting oxidative stress—Endoplasmic reticulum stress—Autophagy signaling pathways
title_fullStr Tempol improves optic nerve histopathology and ultrastructures in cisplatin-induced optic neuropathy in rats by targeting oxidative stress—Endoplasmic reticulum stress—Autophagy signaling pathways
title_full_unstemmed Tempol improves optic nerve histopathology and ultrastructures in cisplatin-induced optic neuropathy in rats by targeting oxidative stress—Endoplasmic reticulum stress—Autophagy signaling pathways
title_short Tempol improves optic nerve histopathology and ultrastructures in cisplatin-induced optic neuropathy in rats by targeting oxidative stress—Endoplasmic reticulum stress—Autophagy signaling pathways
title_sort tempol improves optic nerve histopathology and ultrastructures in cisplatin induced optic neuropathy in rats by targeting oxidative stress endoplasmic reticulum stress autophagy signaling pathways
topic optic neuropathy
autophagy
endoplasmic reticulum stress
tempol
cisplatin (Cis)
url https://www.frontiersin.org/articles/10.3389/fncel.2023.1256299/full
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