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Melatonin decreases the oxidative stress produced by 2,4-dichlorophenoxyacetic acid in rat cerebellar granule cells

  • B. Bongiovanni
  • P. De Lorenzi
  • A. Ferri
  • C. Konjuh
  • M. Rassetto
  • A. M. Evangelista De Duffard
  • D. P. Cardinali
  • R. Duffard
Article

Abstract

2,4-Dichlorophenoxyacetic acid (2,4-D) is one of the most widely used herbicides due to its relatively moderate toxicity and to its biodegrad-ability in the soil. In toxic concentrations, 2,4- D displays strong neurotoxicity, partly due to generation of free radicals. Since melatonin has remarkable antioxidant properties, the objective of this study was to assess to what extent it was effective in preventing the 2,4-D effect on redox balance of rat cerebellar granule cells (CGC) in vitro. Cellular viability, generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS), reduced glutathione (GSH) levels, and the activities of the antioxidant enzymes Cu/ Zn-superoxide dismutase (Cu/Zn-SOD), Mn-SOD, selenium-glutathione peroxidase (Se-GPx) and catalase (CAT) were measured in CGC exposed to 2,4-D and/or melatonin for 48 h. In CGC cultures exposed to 2,4-D, cell viability, GSH levels and CAT activity decreased significantly whereas ROS generation and Se-GPx activities were augmented. Except for Se-GPx activity, all these changes were counteracted by the concomitant addition of 0.1 or 0.5 mM melatonin. In addition, incubation of CGC with melatonin alone resulted in augmentation of cell viability, GSH levels and Se-GPx activity. RNS generation and SOD activity remained unaffected by either treatment. Since melatonin was able to counteract most of redox changes produced by 2,4-D in CGC in culture, the experimental evidence reported further support the efficacy of melatonin to act as a neuroprotector.

Keywords

2,4-Dichlorophenoxyacetic acid Herbicides Melatonin Free radicals Cerebellar granule cells 

Abbreviations

2,4-D

2,4-Dichlorophenoxyacetic acid

CAT

catalase

CGC

Cerebellar granule cells

CNS

Central nervous system

Cu/Zn-SOD

Cu/Zn-superoxide dismutase

DCF

2′,7′-dichlorofluorescein

DCFH

2′7′-dichlorofluorescin

GSH

reduced glutathione

Mn-SOD

Mn-superoxide dismutase

MTT

3-(4,5-dimethylthiazol-2-eyl)-2,5-diphenyl tetrazolium bromide

NMDA

N-methyl-D-aspartate

NO

nitric oxide

RNS

reactive nitrogen species

ROS

reactive oxygen species

Se-GePx

selenium-glutathione peroxidase

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Copyright information

© FP Graham Publishing Co 2007

Authors and Affiliations

  • B. Bongiovanni
    • 1
  • P. De Lorenzi
    • 1
  • A. Ferri
    • 1
  • C. Konjuh
    • 1
  • M. Rassetto
    • 1
  • A. M. Evangelista De Duffard
    • 1
  • D. P. Cardinali
    • 2
  • R. Duffard
    • 1
  1. 1.Laboratorio de Toxicología Experimental (LATOEX) Facultad de Ciencias Bioquímicas y FarmacéuticasUniversidad Nacional de RosarioRosarioArgentina
  2. 2.Departamento de Fisiología, Facultad de MedicinaUniversidad de Buenos AiresBuenos AiresArgentina

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