Omega-3 polyunsaturated fatty acids in large doses attenuate seizures, cognitive impairment, and hippocampal oxidative DNA damage in young kindled rats

Neurosci Lett. 2015 Jan 1:584:173-7. doi: 10.1016/j.neulet.2014.10.003. Epub 2014 Oct 12.

Abstract

Omega-3 (OM3) dietary polyunsaturated fatty acids have promising seizure-protective effects, as well as enhancing effects of cognitive development and memory-related learning. This study aimed to explore the effect of large doses of OM3 on cognitive impairment and hippocampal oxidative DNA damage produced by seizures in epileptic children using a PTZ-kindled young rat model. Cognitive functions, biomarkers of oxidative stress, and DNA damage were assessed in PTZ-kindled young rats (30 mg/kg, i.p. once every other day for 13 injections) pretreated with OM3 (200-500 mg/kg, p.o.). Pretreatment with OM3 at the tested doses significantly attenuated PTZ-induced seizures and decreased cognitive impairment in both passive avoidance and elevated plus maze tests in the PTZ-kindled rats. Moreover, OM3 significantly attenuated the increase in hippocampal malondialdehyde and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels, as well as the decrease in reduced glutathione (GSH) levels and GSH-peroxidase activity induced by PTZ kindling, in a dose-related manner. Relatively large dose levels of OM3 (200-500 mg/kg) effectively attenuated seizures and their associated cognitive deficits, and reduced oxidative stress and hippocampal DNA damage in PTZ-kindled young rats.

Keywords: DNA damage; Epilepsy and cognition; Omega-3; Oxidative stress; Passive avoidance; Pentylenetetrazole kindling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Avoidance Learning / drug effects
  • Cognition Disorders / metabolism
  • Cognition Disorders / prevention & control*
  • Cognition Disorders / psychology
  • DNA Damage / drug effects*
  • Dose-Response Relationship, Drug
  • Fatty Acids, Omega-3 / pharmacology*
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Kindling, Neurologic
  • Male
  • Oxidative Stress / drug effects
  • Rats, Wistar
  • Seizures / metabolism
  • Seizures / prevention & control*
  • Seizures / psychology

Substances

  • Fatty Acids, Omega-3