MELATONIN MAINTAINS GLUTATHIONE HOMEOSTASIS IN KAINIC ACID-EXPOSED RAT-BRAIN TISSUES

Reduced glutathione (GSH) is a key component of the cellular defense c ascade against injury caused by reactive oxygen species, Because kaini c acid (KA) neurotoxicity is probably mediated at least in part by oxi dative stress, we examined the influence of KA treatment on GSH conten t and GSH-related enzyme activities in adult rats, A single injection of KA (10 mg/kg i.p.) time-dependently decreased forebrain GSH (maxima l reduction at 48 h). KA also markedly lowered GSH levels in amygdala and hippocampus, but not in the corpus striatum, which is resistant to KA injury, The pineal secretory product melatonin has been shown to e xert neuroprotective effects against KA-induced excitotoxicity in rats , Melatonin (2.5 mp/kg i.p., administered four times) partially preven ted all. decreases in GSH of KA-treated rats, These neuroprotective ef fects of melatonin may result from a sparing of glutathione reductase, which decreased in KA-treated but not in KA/melatonin-treated animals . Moreover, KA caused a rapid decrease in the GSH content of cultured cerebellar granule neurons but not astrocytes, These cell types both e xpress functional KA receptors, but only the former are sensitive to r eactive oxygen species-dependent KA injury, Melatonin counteracted the changes in GSH induced by KA in cultured cerebellar granule neurons, Our results suggest that melatonin prevents the neurotoxic effects of reactive oxygen species linked to KA receptor activation by maintainin g cellular GSH homeostasis.