Decrease in Oxidative Stress Parameters after Post‐Ischaemic Recombinant Human Erythropoietin Administration in the Hippocampus of Rats Exposed to Focal Cerebral Ischaemia
Author(s) -
MršićPelčić Jasenka,
Pilipović Kristina,
Pelčić Goran,
Vitezić Dinko,
Župan Gordana
Publication year - 2017
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12833
Subject(s) - oxidative stress , erythropoietin , neuroprotection , medicine , ischemia , endocrinology , hippocampus , glutathione peroxidase , superoxide dismutase , nimodipine , thiobarbituric acid , hippocampal formation , pharmacology , brain damage , anesthesia , lipid peroxidation , calcium
Abstract Recombinant human erythropoietin (rhEpo) is a multi‐functional drug with antioxidant potential. However, the underlying molecular mechanisms of its action are still unclear. The purpose of this study was to investigate the effects of rhEpo on the brain infarct volume as well as on the levels of the neuronal damage, oxidative stress parameters and active caspase‐3, nuclear factor erythroid 2‐related factor 2 (Nrf2) and haemeoxygenase‐1 (HO‐1) expressions in the hippocampi of rats exposed to the right middle cerebral artery occlusion (MCAO) for 1 hr. Ischaemic animals received either vehicle or rhEpo (5000 IU/kg, i.p.) immediately or 3 hr after the induction of ischaemia. Sham‐operated, vehicle‐treated animals served as the control group. Rats were killed 24 hr after the onset of the ischaemic or sham experimental procedure. MCAO caused ipsilateral brain infarction within the striatum and cortex. In the CA1 region of the hippocampi, we did not find significant neuronal loss, but a statistically significant rise in the active caspase‐3 and Nrf2 protein expressions was registered. We detected also significant increases in the hippocampal levels of oxidative stress parameters (thiobarbituric acid‐reactive substances, superoxide dismutase, glutathione peroxidase). Post‐ischaemic administration of rhEpo significantly reduced the brain infarct volume, decreased levels of all tested oxidative stress parameters and increased the Nrf2 expression level. These findings suggest that decrease in oxidative stress parameters in the hippocampus could be an early indicator of post‐ischaemic neuroprotective effect of rhEpo in rats exposed to focal cerebral ischaemia and that this effect could be attributable to additional post‐ischaemic activation of Nrf2 endogenous antioxidant system.
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