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Naringin and Sertraline Ameliorate Doxorubicin-Induced Behavioral Deficits Through Modulation of Serotonin Level and Mitochondrial Complexes Protection Pathway in Rat Hippocampus

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Abstract

The present study was designed to investigate the neuroprotective effect of naringin (NR) alone as well as its combination with sertraline (SRT) against doxorubicin (DOX)-induced neurobehavioral and neurochemical anomalies. DOX (15 mg/kg; i.p.) administration caused behavioral alterations, oxidative stress, neuroinflammation, mitochondrial dysfunction and monoamines alteration in male Wistar rats. NR (50 and 100 mg/kg; i.p.) and SRT (5 mg/kg; i.p.) treatment significantly attenuated DOX-induced anxiety and depressive-like behavior as evident from elevated plus maze (EPM) and modified forced swimming test (mFST), respectively. NR treatment significantly attenuated DOX-induced raised plasma corticosterone (CORT), tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) levels in the hippocampus (HC). Furthermore, we found that combination of NR and SRT regimen ameliorated DOX-induced behavioral anomalies through modulation of the 5-HT level and mitochondrial complexes protection pathway along with alleviation of oxidative stress in the HC region. Therefore, NR treatment alone or in combination with SRT could be beneficial against DOX-induced neurotoxicity.

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Abbreviations

DOX:

Doxorubicin

NR:

Naringin

Sod.CMC:

Sodium carboxymethyl cellulose

SRT:

Sertraline

BBB:

Blood-brain barrier

P-gp:

P-glycoprotein

HC:

Hippocampus

EPM:

Elevated plus maze

mFST:

Modified forced swimming test

TNF-α:

Tumor necrosis factor-alpha

IL-1β:

Interleukin-1 beta

CORT:

Corticosterone

MDA:

Malondialdehyde

GSH:

Glutathione

SOD:

Superoxide dismutase

CAT:

Catalase

SDH:

Succinate dehydrogenase

5-HT:

Serotonin

NE:

Norepinephrine

DA:

Dopamine

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Acknowledgments

We would like to thank All India Council for Technical Education, India for fellowship to Mohit Kwatra for this work. The authors are greatly thankful to University Grants Commission Special Assistance Programme (UGC-SAP), Department of Pharmacology at Poona College of Pharmacy, Pune for technical support. The authors are immensely thankful to Dr. Paritosh Parashar for proof reading this article.

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Author notes

  1. Mohit Kwatra

    Present address: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research Guwahati, Guwahati, Assam, 781032, India

Authors and Affiliations

  1. Neurobehavioral Pharmacology Laboratory, Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi, 110062, India

    Mohit Kwatra, Vikas Kumar, Divya Vohora & Razia Khanam

  2. Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research Guwahati, Guwahati, Assam, 781032, India

    Ashok Jangra, Yogita Sharma & Sahabuddin Ahmed

  3. Department of Toxicology and Cancer Biology, College of Medicine, University of Kentucky, Lexington, KY, 40536, USA

    Murli Mishra

  4. Department of Pharmacology, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Erandwane, Pune, Maharashtra, 411038, India

    Pinaki Ghosh

  5. Department of Pharmacology, Gulf Medical University, Ajman, United Arab Emirates

    Razia Khanam

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Correspondence to Mohit Kwatra.

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Kwatra, M., Jangra, A., Mishra, M. et al. Naringin and Sertraline Ameliorate Doxorubicin-Induced Behavioral Deficits Through Modulation of Serotonin Level and Mitochondrial Complexes Protection Pathway in Rat Hippocampus. Neurochem Res 41, 2352–2366 (2016). https://doi.org/10.1007/s11064-016-1949-2

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