ABSTRACT
OBJECTIVES: In this study, we evaluated the effect of the proanthocyanidins-rich fraction (PRF) obtained from Croton celtidifolius bark in an experimental animal model of spinal cord injury and cell death induced by glutamate. METHODS: Experiments were conducted using adult male Wistar rats (10 weeks old and weighing 270-300g). Experimental groups were randomly allocated into the following groups: spinal cord injury (SCI) + vehicle group: rats were subjected to SCI plus intraperitoneal administration of vehicle (saline 10 ml/kg); SCI + PRF: rats were subjected to SCI plus intraperitoneal administration of PRF (10 mg/kg) at 1 and 6 h after injury and sham operated. KEY FINDINGS: The treatment with the proanthocyanidin-rich fraction significantly improved not only motor recovery and grip force but also H2 O2 or glutamate-induced cell death and reactive oxygen species generation induced by glutamate in dorsal root ganglion cells. In this study we demonstrate that the neuroprotective effect triggered by the proanthocyanidins-rich fraction appears to be mediated in part by the inhibition of N-methyl-D-aspartate-type glutamate receptors. CONCLUSIONS: Taken together, our results demonstrate that PRF treatment ameliorates spinal cord injury and glutamatergic excitotoxicity and could have a potential therapeutic use.
Subject(s)
Croton/chemistry , Glutamic Acid/adverse effects , Neuroprotective Agents/therapeutic use , Phytotherapy , Proanthocyanidins/therapeutic use , Receptors, Glutamate/metabolism , Spinal Cord Injuries/drug therapy , Animals , Antioxidants/pharmacology , Antioxidants/therapeutic use , Cell Death/drug effects , Disease Models, Animal , Ganglia, Spinal/drug effects , Ganglia, Spinal/metabolism , Male , Movement/drug effects , Muscle Strength/drug effects , Neuroprotective Agents/pharmacology , Plant Bark , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Proanthocyanidins/pharmacology , Rats, Wistar , Reactive Oxygen Species/metabolism , Spinal Cord Injuries/physiopathologyABSTRACT
Some studies suggest that mitochondrial dysfunction may be related to the pathophysiology of bipolar disorder. In this work, we evaluated the activity of citrate synthase in rats, and the effects of the treatment with mood stabilizers (lithium and valproate) on the enzyme activity. In the first experiment (reversal treatment), amphetamine or saline were administered to rats for 14 days, and between day 8 and 14, rats were treated with either lithium, valproate or saline. In the second experiment (prevention treatment), rats were pretreated with lithium, valproate or saline, and between day 8 and 14, rats were administered amphetamine or saline. In reversal and prevention models, amphetamine administration significantly inhibited citrate synthase activity in rat hippocampus. In amphetamine-pretreated animals, valproate administration reversed citrate synthase activity inhibition induced by amphetamine. In the prevention model, pretreatment with lithium prevented amphetamine-induced citrate synthase inhibition. Our results showed that amphetamine inhibited citrate synthase activity and that valproate reversed and lithium prevented the enzyme inhibition.
