Potent neuroprotective role of novel melatonin derivatives for management of central neuropathy induced by acrylamide in rats

Eur J Med Chem. 2010 Nov;45(11):5452-9. doi: 10.1016/j.ejmech.2010.09.017. Epub 2010 Sep 17.

Abstract

Acrylamide (ACR) has been shown to be a neurotoxic agent for both laboratory animals and human. The present study aimed at synthesizing new functionalized melatonin derivatives bearing promising heterocyclic moiety that could be expected to have protective effect against ACR-induced neurotoxicity in adult female rats. The novel melatonin derivatives 4, 6, 7 and 11 were synthesized and their chemical structures were confirmed by studying their analytical and spectral data. The administration of ACR [i.p., 50 mg kg(-1) body weight (b. wt.)] alone resulted in significant increase in brain malondialdehyde level (MDA) and lactate dehydrogenase (LDH) activity whereas it caused significant decrease in brain monoamines levels and antioxidant enzymes activity. Treatment with melatonin derivatives 4, 6, 7 and 11 (i.p., 50 mg kg(-1) b. wt) prior to ACR produced significant decrease in brain MDA level and LDH activity with concomitant significant increase in brain monoamines and antioxidant enzymes activity. It could be concluded that the new synthesized melatonin derivatives exhibited promising protective activity against ACR-induced neurotoxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrylamide / toxicity*
  • Animals
  • Antioxidants / metabolism
  • Brain / enzymology
  • Brain / metabolism
  • Female
  • L-Lactate Dehydrogenase / metabolism
  • Magnetic Resonance Spectroscopy
  • Malondialdehyde / metabolism
  • Melatonin / analogs & derivatives
  • Melatonin / therapeutic use*
  • Nervous System Diseases / chemically induced
  • Nervous System Diseases / drug therapy*
  • Nervous System Diseases / metabolism
  • Oxidants / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Spectrometry, Mass, Electrospray Ionization
  • Spectrophotometry, Infrared

Substances

  • Antioxidants
  • Oxidants
  • Acrylamide
  • Malondialdehyde
  • L-Lactate Dehydrogenase
  • Melatonin