Targeting Oxidative Stress, Autophagy, and Apoptosis by Quercetin to Ameliorate Cisplatin-induced Peripheral Neuropathy in Rats

Heba A Mahmoud; Hemat E El Horany; Marwa Aboalsoud; Rania Nagi Abd-Ellatif; Amal Ahmed El Sheikh; Alshimaa Aboalsoud

doi:10.4103/jmau.jmau_78_22

Targeting Oxidative Stress, Autophagy, and Apoptosis by Quercetin to Ameliorate Cisplatin-induced Peripheral Neuropathy in Rats

J Microsc Ultrastruct. 2023 Jan 5;11(2):107-114. doi: 10.4103/jmau.jmau_78_22. eCollection 2023 Apr-Jun.

Authors

Heba A Mahmoud¹, Hemat E El Horany^{2

3}, Marwa Aboalsoud⁴, Rania Nagi Abd-Ellatif², Amal Ahmed El Sheikh⁵, Alshimaa Aboalsoud¹

Affiliations

¹ Department of Pharmacology, Faculty of Medicine, Tanta University, Tanta, Egypt.
² Department of Medical Biochemistry, Faculty of Medicine, Tanta University, Tanta, Egypt.
³ Department of Biochemistry, College of Medicine, Hail University, Hail, Dammam, Saudi Arabia.
⁴ Department of Clinical Oncology, Faculty of Medicine, Tanta University, Tanta, Egypt.
⁵ Department of Anatomy, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.

Abstract

Background: Quercetin is a flavonoid, with antioxidant and autophagy-modulating activities. Cisplatin is one of the platinum-based anticancer drugs. Early development of peripheral neuropathy as an adverse effect of cisplatin interferes with the continuation of therapy. Oxidative stress and autophagy impairment may play a role.

Aim: This study aimed to explore the possible protective effects of quercetin against cisplatin-induced peripheral neuropathy.

Methods: Twenty-four male Wistar rats were divided into three groups: Group 1 (control group) and Group 2 (cisplatin group) where peripheral neuropathy was induced using single ip injection of cisplatin. Group 3 (cisplatin + quercetin group) received single ip injection of cisplatin and was then treated with quercetin for 14 days. At the end of the experiment, nociception was evaluated by tail immersion test, and then, blood was collected for analysis of nerve growth factor. Sciatic nerve was used to assess histopathological changes and light chain 3-II by immunohistochemical staining. Reduced glutathione, malondialdehyde, mTOR, and caspase-3 were estimated in sciatic nerve tissue homogenate.

Results: This research work revealed that quercetin significantly improved cisplatin-induced nociceptive impairment, attenuated cisplatin-induced oxidative stress, autophagy, and apoptosis to protect against neuronal death.

Conclusion: From the current study, quercetin can act as a promising protective agent against cisplatin-induced peripheral neuropathy.

Keywords: Apoptosis; autophagy; cisplatin; neuropathy; quercetin.