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

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

doi:10.3389/fncel.2023.1256299

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

Front Cell Neurosci. 2023 Oct 5:17:1256299. doi: 10.3389/fncel.2023.1256299. eCollection 2023.

Affiliations

¹ Human Anatomy and Embryology Department, Faculty of Medicine, Zagazig University Egypt, Zagazig, Egypt.
² Department of Biology, Faculty of Agriculture, University of Life Sciences, King Mihai I" from Timisoara [ULST], Timisoara, Romania.
³ Medical Physiology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
⁴ Department of Animal Physiology and Biochemistry, Faculty of Veterinary Medicine, Badr University in Cairo, Badr City, Egypt.
⁵ Department of Physiology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt.
⁶ Department of Pharmacology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt.
⁷ Laboratory of Biotechnology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt.

Abstract

Introduction: Optic 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.

Methods: Forty-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.

Results: Histopathological 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.

Conclusions: Based 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.

Keywords: autophagy; cisplatin (Cis); endoplasmic reticulum stress; optic neuropathy; tempol.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research received no external funding, and the APC was funded by the project 6PFE of the University of Life Sciences King Mihai I from Timisoara and the Research Institute for Biosecurity and Bioengineering from Timisoara, Romania.