Time-course correlation of early toxic events in three models of striatal damage: modulation by proteases inhibition.

Metabolic alterations in the nervous system can be produced at early stages of toxicity and are linked with oxidative stress, energy depletion and death signaling. Proteases activation is responsible for triggering deadly cascades during cell damage in toxic models. In this study we evaluated the early time-course of toxic events (oxidative damage to lipids, mitochondrial dysfunction and LDH leakage, all at 1, 3 and 6h) in rat striatal slices exposed to quinolinic acid (QUIN, 100 microM) as an excitotoxic/pro-oxidant model, 3-nitropropionic acid (3-NP, 1mM) as an inhibitor of mitochondrial succinate dehydrogenase, and a combined model produced by the co-administration of these two toxins at subtoxic concentrations (21 and 166 microM for QUIN and 3-NP, respectively).

Antioxidant strategy to rescue synaptosomes from oxidative damage and energy failure in neurotoxic models in rats: protective role of S-allylcysteine.

The functional preservation of nerve endings since the early stages of toxicity in a given damaging insult-either acute or chronic-by means of antioxidant and neuroprotective agents is a primary need to design therapeutic strategies for neurodegenerative disorders, with particular emphasis on those diseases with excitotoxic and depleted energy metabolism components. S-allylcysteine (SAC), a well-known antioxidant agent, was tested as a post-treatment in different in vitro and in vivo neurotoxic models. Quinolinic acid (QUIN) was used as a typical excitotoxic/pro-oxidant inducer, 3-nitropropionic acid (3-NP) was employed as a mitochondrial function inhibitor, and their combination (QUIN + 3-NP) was also evaluated in in vitro studies.

Protective effect of tert-butylhydroquinone on the quinolinic-acid-induced toxicity in rat striatal slices: role of the Nrf2-antioxidant response element pathway.

Tert-butylhydroquinone (tBHQ) is a xenobiotic with reported antioxidant properties. tBHQ has been shown to induce nuclear translocation of the transcription factor NF-E2-related factor 2 (Nrf2) to further activate the antioxidant response element (ARE). In turn, the Nrf2/ARE pathway is responsible for the induction of phase 2 antioxidant enzymes that detoxify oxidant promoters from different toxic insults.

Early nerve ending rescue from oxidative damage and energy failure by L: -carnitine as post-treatment in two neurotoxic models in rat: recovery of antioxidant and reductive capacities.

Cell rescue is a primary need during acute and chronic insults to the central nervous system. Functional preservation during the early stages of toxicity in a given degenerative event may represent a significant amelioration of detrimental processes linked to neuronal cell loss. Excitotoxicity and depleted cellular energy are toxic events leading to cell death in several neurodegenerative disorders.

Targeting oxidative/nitrergic stress ameliorates motor impairment, and attenuates synaptic mitochondrial dysfunction and lipid peroxidation in two models of Huntington's disease.

In this study, we reproduced two toxic models resembling some motor/kinetic deficits of Huntington's disease induced by bilateral intrastriatal injections of either quinolinic acid (QUIN, 120 nmol/microl per side) or 3-nitropropionic acid (3-NP, 250 nmol/microl per side) to rats. Motor skills (including total distance walked/traveled and total horizontal and vertical activities) were evaluated in a box-field system at 1 and 7 days post-lesion. In order to investigate whether these alterations were associated with the oxidative/nitrergic stress evoked by the nitrogen reactive species peroxynitrite (ONOO(-)) in the striatum, some rats were pretreated with the ONOO(-) decomposition catalyst iron porphyrinate (Fe(TPPS), 10 mg/kg, i.