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

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)S197-S207
JournalPharmacognosy Magazine
Volume14
Issue number55
DOIs
Publication statusPublished - 01-04-2018

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Doxorubicin
Episodic Memory
Locomotion
Reactive Oxygen Species
Flow Cytometry
Acridine Orange
Ethidium
Memory Disorders
Neurites
In Vitro Techniques
Cognitive Dysfunction
naringin
Bromides
Flavonoids
Hydrocortisone
Wistar Rats
Cell Cycle
Therapeutics
Apoptosis
Staining and Labeling

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science
  • Drug Discovery

Cite this

Ramalingayya, Grandhi Venkata ; Nayak, Pawan G. ; Shenoy, Rekha R. ; Mallik, Sanchari Basu ; Gourishetti, Karthik ; Hussain, Shalam M. ; Rao, Chamallamudi Mallikarjuna ; Nandakumar, Krishnadas. / Naringin ameliorates doxorubicin-induced neurotoxicity in vitro and cognitive dysfunction in vivo. In: Pharmacognosy Magazine. 2018 ; Vol. 14, No. 55. pp. S197-S207.
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abstract = "Objectives: The primary objective of the study was to study the neuroprotective potential of naringin (NAR) against doxorubicin (DOX){\^a}€‘induced neurotoxicity in vitro and DOX{\^a}€‘induced cognitive deficits (chemobrain) in vivo. Materials and Methods: In vitro methods, viz., 3{\^a}€‘[4,5dimethylthiazol{\^a}€‘2{\^a}€‘yl]{\^a}€‘2,5{\^a}€‘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{\^a}€‘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{\^a}€‘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{\^a}€‘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.",
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Naringin ameliorates doxorubicin-induced neurotoxicity in vitro and cognitive dysfunction in vivo. / Ramalingayya, Grandhi Venkata; Nayak, Pawan G.; Shenoy, Rekha R.; Mallik, Sanchari Basu; Gourishetti, Karthik; Hussain, Shalam M.; Rao, Chamallamudi Mallikarjuna; Nandakumar, Krishnadas.

In: Pharmacognosy Magazine, Vol. 14, No. 55, 01.04.2018, p. S197-S207.

Research output: Contribution to journalArticle

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T1 - Naringin ameliorates doxorubicin-induced neurotoxicity in vitro and cognitive dysfunction in vivo

AU - Ramalingayya, Grandhi Venkata

AU - Nayak, Pawan G.

AU - Shenoy, Rekha R.

AU - Mallik, Sanchari Basu

AU - Gourishetti, Karthik

AU - Hussain, Shalam M.

AU - Rao, Chamallamudi Mallikarjuna

AU - Nandakumar, Krishnadas

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Y1 - 2018/4/1

N2 - 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.

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