ORIGINAL PAPER Paraquat-induced Oxidative Stress in Drosophila melanogaster : Effects of Melatonin, Glutathione, Serotonin, Minocycline, Lipoic Acid and Ascorbic Acid Ernesto Bonilla Æ Shirley Medina-Leendertz Æ Virginia Villalobos Æ Leunardy Molero Æ Aquiles Boho ´ rquez Accepted: 5 October 2006 / Published online: 4 November 2006 Ó Springer Science+Business Media, LLC 2006 Abstract The efficacy of melatonin, glutathione, serotonin, minocycline, lipoic acid and ascorbic acid in counteracting the toxicity of paraquat in Drosophila melanogaster was examined. Male Oregon wild strain flies were fed for 5 days with control food or food containing the test substance. They were transferred in groups of five to vials containing only filter paper soaked with 20 mM paraquat in 5% sucrose solution. Survival was determined 24 and 48 h later. All the substances assayed increased the survival of D. mela- nogaster. At equimolar concentrations (0.43 mM) melatonin was more effective than serotonin, lipoic acid and ascorbic acid. However, lower concentrations of glutathione (0.22 mM) and minocycline (0.05 mM) were as efficient as melatonin. The highest survival rate (38.6%) after 48 h of paraquat treatment was found with 2.15 mM of lipoic acid. No synergistic effect of melatonin with glutathione, serotonin, minocycline, lipoic acid and ascorbic acid was detected. Keywords Paraquat Á Drosophila melanogaster Á Melatonin Á Glutathione Á Serotonin Á Minocycline Á Lipoic acid Á Ascorbic acid Introduction Paraquat (1,1¢dimethyl-4-4¢-bipyridynium dichloride) a quaternary nitrogen herbicide, is a highly toxic sub- stance for humans and animals; many cases of acute poisoning and death have been reported [1]. The toxicity of paraquat is due to the generation of the superoxide anion which can lead to the synthesis of more toxic reactive oxygen species (ROS) such as hydroxyl radicals and hydrogen peroxide [2]. On the other hand, the oxidation of reduced nicotinamide adenine dinucleotide phosphate (NADPH) as a con- sequence of paraquat administration results in the disruption of biochemical processes requiring NADPH [3, 4]. Melatonin (N-acetyl-5-methoxytryptamine) is a potent hydroxyl radicals scavenger [5]. This hormone crosses the cell membrane to enter the cytosol and it also has access to every subcellular compartment due to its high solubility in lipids and its hydrophilicity [6]. Tan et al. [7] presented evidence of the ability of endogenous melatonin to scavenge free radicals. They demonstrated, after surgical removal of the pineal glands of rats, that physiological melatonin concentra- tions are sufficient to partially reduce the destruction of DNA by free radicals. Glutathione (c-glutamyl-cysteinyl-glycine) is an important source of reducing equivalents during oxidative stress [8]. Glutathione (GSH) is synthesized from cysteine, glutamate and glycine by the action of the enzymes glutamate–cysteine ligase and glutathione synthetase. GSH may be oxidized to its disulfide GSSG. This oxidation is among the earliest cellu- lar responses to an increase in the production of ROS [9]. The glutathione disulfide glutathione couple E. Bonilla (&) Neurochemistry Section, Instituto de Investigaciones Clı ´nicas ‘‘Dr. Ame ´ rico Negrette’’, Universidad del Zulia, Apartado 23, Maracaibo 4001, Venezuela e-mail: ebonillaro@yahoo.com E. Bonilla Á S. Medina-Leendertz Centro de Investigaciones Biome ´ dicas, IVIC-Zulia, Maracaibo, Venezuela V. Villalobos Á L. Molero Á A. Boho ´ rquez Biology Department, Facultad Experimental de Ciencias, Universidad del Zulia, Maracaibo, Venezuela Neurochem Res (2006) 31:1425–1432 DOI 10.1007/s11064-006-9194-8 123