Guanosine prevents thermal hyperalgesia in a rat model of peripheral mononeuropathy.
ABSTRACT It is well known that adenine-based purines exert multiple effects on pain transmission. Less attention has been given, however, to the antinociceptive effects of guanine-based purines. The aim of this study was to investigate the effects of intraperitoneal administration of guanosine on a rat model of peripheral mononeuropathy. Additionally, investigation of the mechanism of action of guanosine, its general toxicity and measurements of central nervous system purine levels were performed. Rats received an intraperitoneal administration of vehicle (0.1 mM NaOH) or guanosine (up to 120 mg.kg(-1)) in an acute or chronic regimen. Guanosine significantly reduced thermal hyperalgesia on the ipsilateral side of the sciatic nerve ligation. Additionally, guanosine prevented locomotor deficits and body weight loss induced by the mononeuropathy. Acute systemic administration of guanosine caused an approximately 11-fold increase on central nervous system guanosine levels, but this effect was not observed after chronic treatment. Chronic guanosine administration prevented the increase on cortical glutamate uptake but not the decrease in spinal cord glutamate uptake induced by the mononeuropathy. No significant general toxicity was observed after chronic exposure to guanosine. This study provides new evidence on the mechanism of action of guanine-based purines, with guanosine presenting antinociceptive effects against a chronic pain model. PERSPECTIVE: This study provides a new role for guanosine: chronic pain modulation. Guanosine presents as a new target for future drug development and might be useful for treatment of neuropathic pain.
- SourceAvailable from: Adriano M de Assis[Show abstract] [Hide abstract]
ABSTRACT: It is well known that glutamatergic excitotoxicity and oxidative stress are implicated in the pathogenesis of hepatic encephalopathy (HE). The nucleoside guanosine exerts neuroprotective effects through the antagonism against glutamate neurotoxicity and antioxidant properties. In this study, we evaluated the neuroprotective effect of guanosine in an animal model of chronic HE. Rats underwent bile duct ligation (BDL) and 2 weeks later they were treated with i.p. injection of guanosine 7.5 mg/kg once a day for 1-week. We evaluated the effects of guanosine in HE studying several aspects: a) animal behavior using open field and Y-maze tasks; b) brain rhythm changes in electroencephalogram (EEG) recordings; c) purines and glutamate levels in the cerebral spinal fluid (CSF); and d) oxidative stress parameters in the brain. BDL rats presented increased levels of glutamate, purines and metabolites in the CSF, as well as increased oxidative damage. Guanosine was able not only to prevent these effects but also to attenuate the behavioral and EEG impairment induced by BDL. Our study shows the neuroprotective effects of systemic administration of guanosine in a rat model of HE and highlights the involvement of purinergic system in the physiopathology of this disease.Metabolic Brain Disease 05/2014; · 2.33 Impact Factor
Article: Letter to the Editor.Cell Biochemistry and Function 10/2012; · 1.85 Impact Factor
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ABSTRACT: Chronic cerebral hypoperfusion contributes to a cognitive decline related to brain disorders. Its experimental model in rats is a permanent bilateral common carotid artery occlusion (2VO). Overstimulation of the glutamatergic system excitotoxicity due to brain energetic disturbance in 2VO animals seems to play a pivotal role as a mechanism of cerebral damage. The nucleoside guanosine (GUO) exerts extracellular effects including antagonism of glutamatergic activity. Accordingly, our group demonstrated several neuroprotective effects of GUO against glutamatergic excitotoxicity. Therefore, in this study, we evaluated a chronic GUO treatment effects in rats submitted to 2VO. We evaluated the animals performance in the Morris water maze and hippocampal damage by neurons and astrocytes immunohistochemistry. In addition, we investigated the cerebrospinal fluid (CSF) brain derived neurotrophic factor (BDNF) and serum S100B levels. Additionally, the purine CSF and plasma levels were determined. GUO treatment did not prevent the cognitive impairment promoted by 2VO. However, none of the 2VO animals treated with GUO showed differences in the hippocampal regions compared to control, while 20% of 2VO rats not treated with GUO presented loss of pyramidal neurons and increased glial labeling cells in CA1 hippocampal region. In addition, we did not observe differences in CSF BDNF nor serum S100B levels among the groups. Of note, both the 2VO surgery and GUO treatment changed the purine CSF and plasma profile. In conclusion, GUO treatment did not prevent the cognitive impairment observed in 2VO animals, but our data suggest that GUO could be neuroprotective against hippocampal damage induced by 2VO.Neurological Sciences 12/2011; 33(5):985-97. · 1.41 Impact Factor