Naringin ameliorates doxorubicin-induced neurotoxicity In vitro and cognitive dysfunction In vivo

Grandhi Venkata Ramalingayya; Pawan G Nayak; Rekha R Shenoy; Sanchari Basu Mallik; Karthik Gourishetti; Shalam M Hussain; Chamallamudi Mallikarjuna Rao; Krishnadas Nandakumar

Articles

Abstract

Pharmacognosy Magazine,2018,14,55s,s197-s207.

DOI:10.4103/pm.pm_364_17

Published:June 2018

Type:Original Article

Authors:

Author(s) affiliations:

Grandhi Venkata Ramalingayya¹, Pawan G Nayak², Rekha R Shenoy², Sanchari Basu Mallik², Karthik Gourishetti², Shalam M Hussain³, Chamallamudi Mallikarjuna Rao², Krishnadas Nandakumar²
¹ Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka; Discovery Biology, Suven Life Sciences Ltd., Hyderabad, Telangana, India
² Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India
³ Department of Pharmacology and Toxicology, Unaizah College of Pharmacy, Qassim University, Al Malida, KSA

Abstract:

Objectives: The primary objective of the study was to study the neuroprotective potential of naringin (NAR) against doxorubicin (DOX)-induced neurotoxicity in vitro and DOX-induced cognitive deficits (chemobrain) in vivo. Materials and Methods: In vitro methods, viz., 3-[4,5dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assay, flow cytometry, acridine orange/ethidium bromide staining, and neuritogenic and reactive oxygen species (ROS) assays, assessed neuroprotective potential of NAR and its aglycone naringenin (NGN) in IMR-32 cells. Chemobrain was developed in Wistar rats on chronic administration of ten cycles of DOX, and episodic memory was assessed using novel object recognition task. Serum cortisol, locomotor activity, and hematological biochemical and histological analysis were carried out. Results: A protective effect of NAR or NGN was observed upon pretreatment with the respective compounds in IMR-32 cells challenged with DOX. Flow cytometry revealed that flavonoids reduced cell cycle changes produced by DOX. In addition, an increase in apoptosis, intracellular ROS generation, and inhibition of neurite growth was noticed in IMR-32 cells with DOX treatment, which was significantly prevented by NAR or NGN pretreatment. Interestingly, NAR (50 mg/kg, p.o.) significantly ameliorated episodic memory deficit associated with DOX without influencing locomotion, upon chronic treatment. NAR also prevented histological changes to major organs observed with DOX. Conclusion: NAR showed neuroprotective potential and may be used as an adjuvant therapy for amelioration of neurocognitive complications associated with chemotherapy in cancer survivors.