title: Naringin and Sertraline Ameliorate Doxorubicin-Induced Behavioral Deficits Through Modulation of Serotonin Level and Mitochondrial Complexes Protection Pathway in Rat Hippocampus.
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.
authors.affiliation: Neurobehavioral Pharmacology Laboratory, Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi, 110062, India. mohitpharmacology@gmail.com.|Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research Guwahati, Guwahati, Assam, 781032, India. mohitpharmacology@gmail.com.
authors.forename: Mohit
authors.initials: M
authors.lastname: Kwatra
authors.affiliation: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research Guwahati, Guwahati, Assam, 781032, India.
authors.forename: Ashok
authors.initials: A
authors.lastname: Jangra
authors.affiliation: Department of Toxicology and Cancer Biology, College of Medicine, University of Kentucky, Lexington, KY, 40536, USA.
authors.forename: Murli
authors.initials: M
authors.lastname: Mishra
authors.affiliation: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research Guwahati, Guwahati, Assam, 781032, India.
authors.forename: Yogita
authors.initials: Y
authors.lastname: Sharma
authors.affiliation: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research Guwahati, Guwahati, Assam, 781032, India.
authors.forename: Sahabuddin
authors.initials: S
authors.lastname: Ahmed
authors.affiliation: Department of Pharmacology, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Erandwane, Pune, Maharashtra, 411038, India.
authors.forename: Pinaki
authors.initials: P
authors.lastname: Ghosh
authors.affiliation: Neurobehavioral Pharmacology Laboratory, Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi, 110062, India.
authors.forename: Vikas
authors.initials: V
authors.lastname: Kumar
authors.affiliation: Neurobehavioral Pharmacology Laboratory, Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi, 110062, India.
authors.forename: Divya
authors.initials: D
authors.lastname: Vohora
authors.affiliation: Neurobehavioral Pharmacology Laboratory, Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi, 110062, India.|Department of Pharmacology, Gulf Medical University, Ajman, United Arab Emirates.
authors.forename: Razia
authors.initials: R
authors.lastname: Khanam
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003345:Corticosterone / Q000097:blood; D003863:Depression / Q000188:drug therapy / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology; D044950:Flavanones / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D020280:Sertraline / Q000494:pharmacology*
chemical_list: D044950:Flavanones; D018696:Neuroprotective Agents; D012701:Serotonin; D004317:Doxorubicin; C005274:naringin; D020280:Sertraline; D003345:Corticosterone
keywords: Doxorubicin; Mitochondrial complexes; Monoamines; Naringin; Oxidative stress; Sertraline