Cerrahi Menopoz ve Kronik Serebral Hipoperfüzyon Oluşturulmuş Sıçanlarda Spironolaktonun Prefrontal Korteks ve Göz Dokularında Glikojen ve Oksidatif Stres Parametreleri Üzerine Etkisi
Abstract
Amaç: Kronik serebral hipoperfüzyon (KSH), ilerleyici hipokampal hasar ve bilişsel bozukluklarla
birlikte vasküler demansa yol açar. KSH retinadaki kan akımında da azalmaya neden olmaktadır. Bu
çalışmanın amacı KSH oluşturulmuş overektomize sıçanlarda spironolaktonun göz ve prefrontal korteks
(PFC) dokularındaki oksidatif stres ve glikojen seviyelerine etkilerini araştırmaktır.
Gereç ve Yöntemler: Wistar Albino cinsi 32 adet dişi sıçan, her grupta 8 adet olacak şekilde rastgele
4 gruba ayrıldı: 1)Kontrol, 2)KSH, 3)KSH+Spironolakton 25mg/kg 4)KSH+Spironolakton 50mg/kg.
Sıçanlara deneyin başlangıcında bilateral ovariektomi (OVX) uygulandı, OVX’ten 5 hafta sonra ortak
bilateral ortak karotid arter oklüzyonu (2VO) ile KSH modeli oluşturuldu. Spironolakton 2VO’dan üç gün
önce ve 2VO’dan sonra 3 hafta boyunca günde 1 kez oral gavaj yoluyla uygulandı. Deney sonunda
doku glikojen, indirgenmiş glutatyon (GSH), malondialdehid (MDA) ve AA düzeyleri ölçüldü. İstatistiksel
analiz ANOVA ve Bonferroni testleri kullanılarak yapıldı.
Bulgular: KSH, PFC’de oksidatif stres belirteçlerinde artışa ve glikojen düzeyinde bir azalmaya neden
oldu. Benzer şekilde KSH göz dokusunda hem glikojen hem de AA düzeyinde azalmaya neden oldu.
Spironolaktonun 25 mg/kg dozu ile tedavi edilen grupta KSH grubuna kıyasla göz AA ve PFC glikojen
düzeyleri azalırken PFC’deki MDA düzeyi artmış olarak bulundu (p<0.05). 50mg/kg spironolakton uygulanan
grupta ise KSH grubuna kıyasla PFC glikojen düzeyleri ve tüm gruplara kıyasla göz glikojen
düzeyi önemli ölçüde arttığı saptandı (p<0.05).
Sonuç: Sonuçlarımız spironolakton uygulamasının KSH oluşturulmuş overektomize sıçanlarda PFC ve
göz dokularında oksidatif stresi azaltarak ve glikojen düzeylerini artırarak KSH’un neden olduğu retinal
ve serebral hasarı azaltmada etkili olabileceğini göstermektedir
References
- 1. Rajeev V, Fann DY, Dinh QN, Kim HA, De Silva TM, Lai MKP, Chen CL, Drummond GR, Sobey CG, Arumugam TV. Pathophysiology of blood brain barrier dysfunction during chronic cerebral hypoperfusion in vascular cognitive impairment. Theranostics. 2022;12(4):1639-1658.
- 2. van der Flier WM, Skoog I, Schneider JA, Pantoni L, Mok V, Chen CLH, Scheltens P. Vascular cognitive impairment. Nat Rev Dis Primers. 2018;4:18003.
- 3. Farkas E, Luiten PG, Bari F. Permanent, bilateral common carotid artery occlusion in the rat: A model for chronic cerebral hypoperfusion-related neurodegenerative diseases. Brain Res Rev. 2007;54(1):162-80.
- 4. Du R, Meng ZY, Wang JL, Wang YL. Efficacy of Osthole in Management of Hypoperfused Retina. J Ophthalmol. 2018;2018:6178347.
Effect of Spironolactone on Glycogen and Oxidative Stress Parameters in Prefrontal Cortex and Eye Tissues in Rats in Which Surgical Menopause and Chronic Cerebral Hypoperfusion Performed
Abstract
Aim: Chronic cerebral hypoperfusion (CCH) leads to vascular dementia with progressive hippocampal damage and cognitive impairments.
CCH also causes a decrease in blood flow in the retina.The aim of this study was to investigate the effects of spironolactone on oxidative
stress and glycogen levels in the eye and prefrontal cortex (PFC) tissues in ovariectomized rats with CCH.
Material and Methods: 32 female Wistar Albino rats were randomly divided into 4 groups, 8 in each group: 1)Control, 2)KSH, 3)
KSH+Spironolactone 25mg/kg 4)KSH+Spironolactone 50mg/kg. The rats underwent bilateral ovariectomy (OVX) at the start of the
experiment, a CCH model was created with permanent occlusion of the common carotid arteries (2VO) 5 weeks after OVX. Spironolactone
was administered by oral gavage three days before 2VO and once daily for 3 weeks after 2VO. At the end of the experiment, tissue glycogen,
reduced glutathione (GSH), malondialdehyde (MDA) and ascorbic acid (AA) levels were measured. Statistical analysis was performed using
ANOVA and Bonferroni tests.
Results: CCH caused an increase in oxidative stress markers and a decrease in glycogen level in PFC. Similarly, CCH caused a decrease
in both glycogen and AA levels in the eye tissue. In the group treated with 25mg/kg spironolactone, the AA and PFC glycogen levels of the
eyes decreased, while the MDA levels in the PFC were increased compared to the CCH group(p<0.05). In the group administered 50mg/kg
spironolactone, PFC glycogen levels and eye glycogen levels were significantly increased compared to the CCH group(p<0.05).
Conclusion: Our results show that spironolactone administration can be effective in reducing retinal and cerebral damage caused by CCH
by reducing oxidative stress and increasing glycogen levels in PFC and eye tissues in ovariectomized rats with CCH
References
- 1. Rajeev V, Fann DY, Dinh QN, Kim HA, De Silva TM, Lai MKP, Chen CL, Drummond GR, Sobey CG, Arumugam TV. Pathophysiology of blood brain barrier dysfunction during chronic cerebral hypoperfusion in vascular cognitive impairment. Theranostics. 2022;12(4):1639-1658.
- 2. van der Flier WM, Skoog I, Schneider JA, Pantoni L, Mok V, Chen CLH, Scheltens P. Vascular cognitive impairment. Nat Rev Dis Primers. 2018;4:18003.
- 3. Farkas E, Luiten PG, Bari F. Permanent, bilateral common carotid artery occlusion in the rat: A model for chronic cerebral hypoperfusion-related neurodegenerative diseases. Brain Res Rev. 2007;54(1):162-80.
- 4. Du R, Meng ZY, Wang JL, Wang YL. Efficacy of Osthole in Management of Hypoperfused Retina. J Ophthalmol. 2018;2018:6178347.
Details
| Primary Language | Turkish |
|---|---|
| Subjects | Health Care Administration |
| Journal Section | Research Article |
| Authors | |
| Publication Date | August 31, 2022 |
| Acceptance Date | July 18, 2022 |
| Published in Issue | Year 2022 Volume: 6 Issue: 2 |
