Progesterone downscales oxidative stress and boosts antioxidant defense capacity in rat model of permanent common carotid artery occlusion
2018
Аутори:
Guševac, IvanaTatalović, Nikola
Zarić, Marina
Martinović, Jelena
Mitrović, Nataša
Blagojević, Duško
Grković, Ivana
Drakulić, Dunja
Тип документа:
Конференцијски прилог (Објављена верзија)
,
© Federation of European Neurocience Societies
Метаподаци
Приказ свих података о документуАпстракт:
Potent neurosteroid progesterone (P4) strongly influences functional recovery in
various models of neurological diseases. However, its protective antioxidative
potential is not well established in stance of chronic cerebral hypoperfusion (CCH)
that induces ischemic milieu in the brain. CCH results in a cascade of events
leading to uncontrolled generation of 4-hydroxynonenal (HNE), a hallmark of
oxidative stress that can be abolished by mitochondrial antioxidant enzyme
manganese superoxide dismutase (MnSOD). Post-ischemic brain regeneration
requires preservation of cerebral blood flow that could be achieved by production of
vasodilatator nitric oxide (NO), synthesized by endothelial NO synthase (eNOS)
whose actions are regulated by phosphorylation at various sites. Decreased
phosphorylation of eNOS at Thr495 during antioxidative response, promotes its
activity and NO production, contributing to neuroprotection. Given the scarcity of
data about P4 antioxidative actions in prefrontal cortex during CCH, current study
assessed the level of HNE and NO, as well as MnSOD activity and the extent of
eNOS phosphorylation at Thr495 in rats subjected to sham operation and injected
with vehicle (commercial flax oil) or animals with permanent occlusion of common
carotid arteries and treated either with vehicle or P4 (1.7 mg/kg/day) for 7 days.
Results indicate that P4 decreases CCH-induced HNE generation and MnSOD
activity, diminishes inactivation of eNOS and increases production of protective NO.
In conclusion, P4 might downscale oxidative stress and boost antioxidant defense
capacity in CCH model, pointing investigated parameters as potential targets of P4
neuroprotective actions. Financially supported by MNTPR RS, grants 173044 and
41014.
Финансирање / пројекти:
- Молекуларни механизми редокс сигналинга у хомеостази, адаптацији и патологији (RS-173014)
- Ћелијска и молекулска основа неуроинфламације: потенцијала циљна места за транслациону медицину и терапију (RS-41014)
У:
- 11th FENS Forum of Neuroscience; 2018 Jul 7-11; Berlin, Germany. Brussels, Belgium: Federation of European Neurocience Societies; 2018. 1971.