Guanosine prevents nitroxidative stress and recovers mitochondrial membrane potential disruption in hippocampal slices subjected to oxygen/glucose deprivation.
Guanosine, the endogenous guanine nucleoside, prevents cellular death induced by ischemic events and is a promising neuroprotective agent. During an ischemic event, nitric oxide has been reported to either cause or prevent cell death. Our aim was to evaluate the neuroprotective effects of guanosine against oxidative damage in hippocampal slices subjected to an in vitro ischemia model, the oxygen/glucose deprivation (OGD) protocol. We also assessed the participation of nitric oxide synthase (NOS) enzymes activity on the neuroprotection promoted by guanosine. Here, we showed that guanosine prevented the increase in ROS, nitric oxide, and peroxynitrite production induced by OGD. Moreover, guanosine prevented the loss of mitochondrial membrane potential in hippocampal slices subjected to OGD. Guanosine did not present an antioxidant effect per se. The protective effects of guanosine were mimicked by inhibition of neuronal NOS, but not of inducible NOS. The neuroprotective effect of guanosine may involve activation of cellular mechanisms that prevent the increase in nitric oxide production, possibly via neuronal NOS.
Programa de Pós-Graduação em Bioquímica, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
Daniel T
DT
Thomaz
Programa de Pós-Graduação em Neurociências, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
Tharine A
TA
Dal-Cim
Programa de Pós-Graduação em Neurociências, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
Wagner C
WC
Martins
Programa de Pós-Graduação em Bioquímica, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
Maurício Peña
MP
Cunha
Programa de Pós-Graduação em Neurociências, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
Débora
D
Lanznaster
Departamento de Bioquímica, CCB, UFSC, Universidade Federal de Santa Catarina, Trindade, 88040-900, Florianópolis, SC, Brazil.|Programa de Pós-Graduação em Bioquímica, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.|Programa de Pós-Graduação em Neurociências, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
Andreza F
AF
de Bem
Departamento de Bioquímica, CCB, UFSC, Universidade Federal de Santa Catarina, Trindade, 88040-900, Florianópolis, SC, Brazil. carla.tasca@ufsc.br.|Programa de Pós-Graduação em Bioquímica, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil. carla.tasca@ufsc.br.|Programa de Pós-Graduação em Neurociências, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil. carla.tasca@ufsc.br.
Carla I
CI
Tasca
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D006151:Guanosine / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*
D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D006151:Guanosine; D019001:Nitric Oxide Synthase; D005947:Glucose
Guanosine; Hippocampal slices; Nitric oxide synthase; Nitroxidative stress; Oxygen/glucose deprivation; Peroxynitrite