Antioxidant and pro-oxidant properties of boldine on hippocampal slices exposed to oxygen-glucose deprivation in vitro.
Boldine is one of the most potent natural antioxidants and displays some important pharmacological activities, such as cytoprotective and anti-inflammatory activities, which may arise from its free radical scavenging properties. Given that the pathogenesis of brain ischemia/reperfusion has been associated with an excessive generation of oxygen free radicals, the aim of this study was to evaluate the neuroproperties of boldine using hippocampal slices from Wistar rats exposed to oxygen and glucose deprivation (OGD), followed by reoxygenation, to mimic an ischemic condition. The OGD ischemic condition significantly impaired cellular viability, increased lactate dehydrogenase (LDH) leakage and increased free radical generation. In non-OGD slices, incubation with 100microM boldine significantly increased LDH released into incubation media and decreased mitochondrial activity, suggesting an increase of tissue damage caused by boldine. However, slices incubated with 10microM boldine during and after OGD exposure had significantly increased cellular viability with no effect on cell damage. Total reactive antioxidant potential (TRAP) levels measured for this alkaloid showed an antioxidant potential three times higher than Trolox, which acts as a peroxyl radical scavenger. Moreover, boldine prevented the increase in lipoperoxidation levels induced by ischemia, but higher concentrations potentiated this parameter. These results confirm the potent antioxidant properties of this alkaloid, and add evidence to support the need for further investigations in order to confirm the potential pro-oxidant effects of boldine at higher doses.
Konrath
Eduardo L
EL
Curso de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Santin
Katiane
K
Nassif
Melissa
M
Latini
Alexandra
A
Henriques
Amélia
A
Salbego
Christianne
C
D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001060:Aporphines / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000172:deficiency*; D006624:Hippocampus / Q000187:drug effects*; D000860:Hypoxia / Q000473:pathology*; D066298:In Vitro Techniques; D008297:Male; D056913:Mediator Complex Subunit 1; D010100:Oxygen / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D000975:Antioxidants; D001060:Aporphines; C538857:Med1 protein, rat; D056913:Mediator Complex Subunit 1; D017392:Thiobarbituric Acid Reactive Substances; D014157:Transcription Factors; C011686:boldine; D005947:Glucose; D010100:Oxygen