Melatonin and amphetamine a potential neuroprotector agents against 2,4-dichlorophenoxyacetic acid injured cerebellar granule cells in cultures

BONGIOVANNI BETTINA

Córdoba

Congreso; XXXIII Reunión Anual de la Sociedad Argentina de Farmacología Experimental (SAFE); 2006

Sociedad Argentina de Farmacología Experimental (SAFE)

2,4-Dichlorophoxyacetic (2,4-D), a worldwide-used herbicide, has been associated with a range of adverse health effects on human being and different animal species. We laboratory has previously reported apoptosis in rat cerebellar granule cell (CGC) cultures by 2,4-D, a process generally believed to be mediated by oxidative stress. Since melatonin has remarkable antioxidant properties and amphetamine has accelerate recovery of function in animals with brain injury, the objective of this study was to determine if the 2,4-D (1 mM) toxicity mechanism involves an alteration in the oxidative cellular homeostasis and if melatonin or d-amphetamine acts as a neuronal protector. Cellular viability, generation of reactive oxygen (ROS) and nitrogen (RNS) species, reduced glutathione (GSH) levels, and the activities of the antioxidant enzymes were measured. In CGC exposed to 2,4-D, cell viability, GSH levels and catalase activity decreased significantly whereas ROS generation and selenium-glutathione peroxidase activity augmented. Whereas, these effects of were partly reverted in cultures exposed to 2,4-D plus melatonin (0.1 and 0.5 mM) or d-amphetamine (1 and 10 uM). In conclusion, melatonin and amphetamine could act as neuroprotector of the 2,4-D toxic effects because they decrease the oxidative stress and cell death.