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

Neurochem Res. 2016 Sep;41(9):2352-66. doi: 10.1007/s11064-016-1949-2. Epub 2016 May 21.


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.

Keywords: Doxorubicin; Mitochondrial complexes; Monoamines; Naringin; Oxidative stress; Sertraline.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects*
  • Corticosterone / blood
  • Depression / drug therapy
  • Depression / metabolism
  • Doxorubicin / pharmacology
  • Flavanones / pharmacology*
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Male
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Neuroprotective Agents / pharmacology
  • Oxidative Stress / drug effects
  • Rats, Wistar
  • Serotonin / metabolism*
  • Sertraline / pharmacology*


  • Flavanones
  • Neuroprotective Agents
  • Serotonin
  • Doxorubicin
  • naringin
  • Sertraline
  • Corticosterone