Melatonin protects against oxygen and glucose deprivation by decreasing extracellular glutamate and Nox-derived ROS in rat hippocampal slices.
Therapeutic interventions on pathological processes involved in the ischemic cascade, such as oxidative stress, neuroinflammation, excitotoxicity and/or apoptosis, are of urgent need for stroke treatment. Melatonin regulates a large number of physiological actions and its beneficial properties have been reported. The aim of this study was to investigate whether melatonin mediates neuroprotection in rat hippocampal slices subjected to oxygen-glucose-deprivation (OGD) and glutamate excitotoxicity. Thus, we describe here that melatonin significantly reduced the amount of lactate dehydrogenase released in the OGD-treated slices, reverted neuronal injury caused by OGD-reoxygenation in CA1 and CA3 hippocampal regions, restored the reduction of GSH content of the hippocampal slices induced by OGD, and diminished the oxidative stress produced in the reoxygenation period. Furthermore, melatonin afforded maximum protection against glutamate-induced toxicity and reversed the glutamate released almost basal levels, at 10 and 30μM concentration, respectively. Consequently, we propose that melatonin might strongly and positively influence the outcome of brain ischemia/reperfusion.
Paediatric Unit, La Paz University Hospital, Paseo de la Castellana 261, 28046-Madrid, Spain.
Paloma
P
Patiño
Instituto de Investigación Sanitaria, Servicio de Farmacología Clínica, Hospital Universitario de la Princesa, Madrid, Spain; Instituto Teófilo Hernando and Department of Pharmacology, Universidad Autónoma de Madrid, C/Arzobispo Morcillo 4, 28029 Madrid, Spain.
Esther
E
Parada
Instituto de Investigación Sanitaria, Servicio de Farmacología Clínica, Hospital Universitario de la Princesa, Madrid, Spain; Instituto Teófilo Hernando and Department of Pharmacology, Universidad Autónoma de Madrid, C/Arzobispo Morcillo 4, 28029 Madrid, Spain.
Victor
V
Farré-Alins
Pharmacy School, Contestado University, 89460-000 Canoinhas, SC, Brazil.
Simone
S
Molz
EuroEspes Biomedical Research Center, Institute for CNS Disorders and Genomic Medicine, 15166-La Corunna, Spain; Chair of Genomic Medicine, Camilo José Cela University, Madrid, Spain.
Ramón
R
Cacabelos
Laboratory of Medicinal Chemistry, Institute of General Organic Chemistry (CSIC); Juan de la Cierva, 3; 28006-Madrid Spain.
José
J
Marco-Contelles
Instituto de Investigación Sanitaria, Servicio de Farmacología Clínica, Hospital Universitario de la Princesa, Madrid, Spain; Instituto Teófilo Hernando and Department of Pharmacology, Universidad Autónoma de Madrid, C/Arzobispo Morcillo 4, 28029 Madrid, Spain.
Manuela G
MG
López
Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, 88040-900, Florianópolis, SC, Brazil.
Carla I
CI
Tasca
Department of Toxicology and Pharmacology, Faculty of Veterinary Medicine, Complutense University of Madrid, 28040-Madrid, Spain.
Eva
E
Ramos
Department of Toxicology and Pharmacology, Faculty of Veterinary Medicine, Complutense University of Madrid, 28040-Madrid, Spain. Electronic address: manarome@ucm.es.
Alejandro
A
Romero
Instituto de Investigación Sanitaria, Servicio de Farmacología Clínica, Hospital Universitario de la Princesa, Madrid, Spain; Instituto Teófilo Hernando and Department of Pharmacology, Universidad Autónoma de Madrid, C/Arzobispo Morcillo 4, 28029 Madrid, Spain. Electronic address: javier.egea@inv.uam.es.
Javier
J
Egea
D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D003847:Deoxyglucose / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D045604:Extracellular Fluid / Q000187:drug effects*; D005947:Glucose / Q000172:deficiency*; D018698:Glutamic Acid / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*
D000975:Antioxidants; D017382:Reactive Oxygen Species; D018698:Glutamic Acid; D003847:Deoxyglucose; D007770:L-Lactate Dehydrogenase; D005978:Glutathione; D005947:Glucose; D008550:Melatonin; D010100:Oxygen
Cerebral ischemia; Glutamate; Melatonin; Neurotoxicity; OGD-reoxygenation; Rat hippocampal slices