@conference{
author = "Guševac Stojanović, Ivana and Tatalović, Nikola and Veljković, Filip and Martinović, Jelena and Zarić Kontić, Marina and Blagojević, Duško and Stojanović, Zoran and Drakulić, Dunja",
year = "2022",
abstract = "Introduction: Cerebral hypoperfusion (CH), a reduced cerebral blood flow, characteristic for aging and neurodegenerative disorders, might be associated with a pro-oxidative state in the brain due to the generation of reactive oxygen species (ROS) that cause neuronal damage. These overgenerated pro-oxidants might be reduced, disabled and neutralized by the endogenous antioxidant enzymes, including superoxide dismutase (SOD) and catalase (CAT). A sex steroid hormone, progesterone, in several experimental models of neuronal injury exerts anti-oxidative properties upregulating anti-oxidative molecules and thus promoting neuroprotection. However, its efficacy in the state of CH is still unknown and it is necessary to better understand the mechanism underlying this hormone’s neuroprotective effects.
Aim: We investigated whether progesterone is able to modulate CH-induced pro-oxidative/anti-oxidative imbalance, as well as SOD and CAT activities, in the prefrontal cortex of three-month-old male Wistar rats subjected to permanent bilateral common carotid artery occlusion (2VO).
Methods: The appropriate actions were undertaken to reduce the distress of the animals in agreement with the European Community Council Directive of 86/609/EEC and 010/63/EU for animal experiments. All experimental procedures were allowed by the Ethical Committee for the Use of Laboratory Animals of VINČA Institute of Nuclear Sciences - National Institute of thе Republic of Serbia, University of Belgrade, Belgrade, Republic of Serbia (protocol authorization numbers 02/11 and 323-07-04253/2016-05). Following chloral hydrate anaesthesia, 8 rats randomly assigned in 2VO groups were double occluded with 5–0 silk suture, while 4 animals from sham operated group were subjected to the same surgical procedure but without actual ligation of carotid arteries. Four hours following the surgical procedure animals from sham operated group, used as controls, were subcutaneously treated with vehicle (commercial flax oil, 1 mg/kg/day, S + V), while animals in 2VO groups were subjected to either progesterone (1.7 mg/kg/day, 2VO + P) or vehicle (commercial flax oil, 1 mg/kg/day, 2VO + V). Following 7 days lasting treatments, pro-oxidative/anti-oxidative balance was assessed according to the method of Alamdari et al. [1]; while activities of anti-oxidative enzymes were determined as described in the study by Tatalović et al. [2]. One-way analysis of variance (ANOVA) test followed by Tukey’s post hoc test was employed to analyse data. The values of p < 0.05 or less were considered statistically significant.
Results: Obtained results demonstrate that compared to controls, 2VO and vehicle treatment induced a significant increase of pro-oxidants levels (p < 0.01) as well as the activities of both investigated anti-oxidative enzymes, although only the CAT activity was significantly increased (p < 0.05). Following progesterone treatment, pro-oxidants levels were lowered to the control level which caused the difference between the 2VO groups (p < 0.05). In parallel, no statistically significant change in SOD activity was observed, while CAT was upregulated (p < 0.05).
Conclusion: Presented results suggest that in the prefrontal cortex in the state of CH, progesterone, by modulating the CAT activity, downregulates overgenerated reactive species, reduces CH-induced oxidative stress and exerts anti-oxidative outcomes.
The Ministry of Education, Science and Technological Development
Disclosure statement: Financially supported by The Ministry of Education, Science and Technological Development, grants No 451-03-1/2022-14/13 and 451-03-68/2022-14/ 200007 and 13451-03-68/2022-14/ 200175
[1] Alamdari, D.H., Ghayour-Mobarhan, M., Tavallaie, S., Parizadeh, M.R., Moohebati, M., Ghafoori, F., et al., 2008. Prooxidant–antioxidant balance as a new risk factor in patients with angiographically defined coronary artery disease. Clinical Biochemistry 41(6),375–380.
[2] Tatalović, N., Vidonja Uzelac, T., Oreščanin Dušić, Z., Nikolić-Kokić, A., Bresjanac, M., Blagojević, D., 2021. Ibogaine-Mediated ROS/Antioxidant Elevation in Isolated Rat Uterus Is β-Adrenergic Receptors and KATP Channels Mediated. Antioxidants 10(11),1792.",
publisher = "European College of Neuropsychopharmacology (ECNP)",
journal = "The 35th ECNP Congress; 2023 Oct 7-10; Barcelona, Spain",
title = "Progesterone exerts protective effects in rat permanent bilateral common carotid artery occlusion model",
number = "P.0477",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5315"
}
