SİSPLATİN İLE İNDUKLENEN PREMATÜR OVER YETMEZLİĞİ SIÇAN MODELİNDE DİOSMİN UYGULAMASININ ETKİLERİ

Amaç Sisplatin kaynaklı erken yumurtalık yetmezliği (POF) modelinde diosmin uygulamasının biyokimyasal ve histopatolojik potansiyel yararlı etkilerini incelemeyi amaçladık. Gereç ve Yöntem Yirmi sekiz sıçan dört gruba ayrıldı. A Grubu sıçanlar (n:7) plasebo grubu olarak belirlendi. Kalan yirmi bir sıçana, POF modeli oluşturmak için 10 gün boyunca 1.5 mg/kg/gün sisplatin intraperitoneal olarak uygulandı. Daha sonra rastgele 3 alt gruba ayrıldılar. Grup B, sisplatine bağlı yumurtalık yetmezliği grubu olarak belirlendi. POF modeli oluşturulurken C grubu sıçanlara aynı anda 10 gün süreyle 100mg/kg/gün diosmin verildi. D grubuna ise POF modeli oluşturulduktan sonra 10 gün süreyle 100mg/kg/gün diosmin verildi. Yirminci günün sonunda AMH, FSH, SOD ve Estradiol değerlerinin incelenmesi için kan örnekleri alındı. Ayrıca histopatolojik inceleme için sol overler rezeke edildi. Bulgular Sisplatin ile indüklenen grupta, diğer gruplara kıyasla daha düşük SOD, AMH ve E2 seviyeleri izlendi (p0.05). Grup C, grup D ve sham grupları arasında FSH değerlerinde anlamlı (p>0.05) fark gözlenmedi. Grup C ve D arasında sham grubuna göre sekonder folikül ve antral folikül sayısında anlamlı (p>0.05) fark saptanmadı. Primordial folikül sayısı grup C'de grup B'ye göre anlamlı derecede yüksekti (p

Anahtar Kelimeler:

Antimüllerian Hormon, Diosmin, Overyan Folikül, Primer Yumurtalık Yetmezliği

EFFECTS OF DIOSMIN ADMINISTRATION ON CISPLATIN-INDUCED PREMATURE OVARIAN FAILURE IN A RAT MODEL

m We aimed to examine the potential beneficial effects of diosmin administration on cisplatin - induced premature ovarian failure (POF) in a rat model Material and Methods Twenty-eight rats were divided into four groups. Group A rats (n:7) were determined as the sham group. The remaining rats received an intraperitoneal injection of 1.5 mg/kg/day cisplatin for 10 days to create a POF model. Then, they were randomly divided into 3 subgroups. Group B was determined as POF group. Group C rats were given 100mg/kg/day diosmin for 10 days simultaneously while creating POF model. Group D rats were given 100mg/kg/day diosmin for 10 days after POF model was created. Twentieth day blood samples were taken and left ovaries were resected for examination. Results CIS-induced rats showed reduced levels of SOD, AMH and E2 compared to sham group rats (p0.05) between the sham group, group C and D. No significant (p>0.05) difference in FSH value was observed between group C, D and sham groups. There was no significant (p>0.05) difference in the number of secondary and antral follicles between group C and D compared to the sham group. Primordial follicle count was significantly higher in group C than group B (p

Keywords:

Anti-Mullerian Hormone, Diosmin, Ovarian Follicle, Primary Ovarian Insufficiency,

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Referans1. Beck-Peccoz P, Persani L. Premature ovarian failure. Orphanet J Rare Dis. 2006;1:9. Published 2006 Apr 6. doi:10.1186/1750-1172-1-9
Referans2. Mauri D, Gazouli I, Zarkavelis G, et al. Chemotherapy Associated Ovarian Failure. Front Endocrinol (Lausanne). 2020;11:572388. Published 2020 Dec 8. doi:10.3389/fendo.2020.572388
Referans3. Molina JR, Barton DL, Loprinzi CL. Chemotherapy-induced ovarian failure: manifestations and management. Drug Saf. 2005;28(5):401-416. doi:10.2165/00002018-200528050-00004
Referans4. Coulam CB, Adamson SC, Annegers JF. Incidence of premature ovarian failure. Obstet Gynecol. 1986;67(4):604-606.
Referans5. Blumenfeld Z, Evron A. Endocrine prevention of chemotherapy-induced ovarian failure. Curr Opin Obstet Gynecol. 2016;28(4):223-229. doi:10.1097/GCO.0000000000000278
Referans6. Woad KJ, Watkins WJ, Prendergast D, Shelling AN. The genetic basis of premature ovarian failure. Aust N Z J Obstet Gynaecol. 2006;46(3):242-244. doi:10.1111/j.1479-828X.2006.00585.x
Referans7. Bines J, Oleske DM, Cobleigh MA. Ovarian function in premenopausal women treated with adjuvant chemotherapy for breast cancer. J Clin Oncol. 1996;14(5):1718-1729. doi:10.1200/JCO.1996.14.5.1718
Referans8. Huwait E, Mobashir M. Potential and Therapeutic Roles of Diosmin in Human Diseases. Biomedicines. 2022;10(5):1076. Published 2022 May 6. doi:10.3390/biomedicines10051076
Referans9. Gerges SH, Wahdan SA, Elsherbiny DA, El-Demerdash E. Pharmacology of Diosmin, a Citrus Flavone Glycoside: An Updated Review. Eur J Drug Metab Pharmacokinet. 2022;47(1):1-18. doi:10.1007/s13318-021-00731-y
Referans10. Jin H, Yamamoto N, Uchida K, Terai S, Sakaida I. Telmisartan prevents hepatic fibrosis and enzyme-altered lesions in liver cirrhosis rat induced by a choline-deficient L-amino acid-defined diet. Biochem Biophys Res Commun. 2007;364(4):801-807. doi:10.1016/j.bbrc.2007.10.083
Referans11. Yuemaier M, Tuerhong M, Keremu A, et al. Research on Establishment of Abnormal Phlegmatic Syndrome with Premature Ovarian Failure Rat Model and Effects of Balgham Munziq Treatment. Evid Based Complement Alternat Med. 2018;2018:3858209. Published 2018 Mar 26. doi:10.1155/2018/3858209
Referans12. Mirshekar MA, Fanaei H, Keikhaei F, Javan FS. Diosmin improved cognitive deficit and amplified brain electrical activity in the rat model of traumatic brain injury. Biomed Pharmacother. 2017;93:1220-1229. doi:10.1016/j.biopha.2017.07.014
Referans13. Kilicoglu SS, Tanrikulu Y, Kismet K, et al. The effect of diosmin on pancreatic injury induced by hepatic ischemia reperfusion in rats. Bratisl Lek Listy. 2013;114(3):119-124. doi:10.4149/bll_2013_026
Referans14. Ozler A, Turgut A, Soydinç HE, et al. The biochemical and histologic effects of adnexal torsion and early surgical intervention to unwind detorsion on ovarian reserve: an experimental study. Reprod Sci. 2013;20(11):1349-1355. doi:10.1177/1933719113485300
Referans15. Female reproductive system. Young B, Heath WJ, editors. Wheater’s Functional Histology: a text and colour atlas. fourth ed., Sydney: Churchill Livingstone; 2000.
Referans16. Gui H, Jin Y, Lin A, Wang P, Wang Y, Zhu H. Rosmarinic acid relieves cisplatin-induced ovary toxicity in female mice via suppression of oxidative stress and inflammation. J Biochem Mol Toxicol. 2021;35(9):e22839. doi:10.1002/jbt.22839
Referans17. Zhang Z, Liu Q, Yang J, et al. The proteomic profiling of multiple tissue damage in chickens for a selenium deficiency biomarker discovery. Food Funct. 2020;11(2):1312-1321. doi:10.1039/c9fo02861g
Referans18. Yasui K, Baba A. Therapeutic potential of superoxide dismutase (SOD) for resolution of inflammation. Inflamm Res. 2006;55(9):359-363. doi:10.1007/s00011-006-5195-y
Referans19. Eraslan G, Sarıca ZS, Bayram LÇ, Tekeli MY, Kanbur M, Karabacak M. The effects of diosmin on aflatoxin-induced liver and kidney damage. Environ Sci Pollut Res Int. 2017;24(36):27931-27941. doi:10.1007/s11356-017-0232-7
Referans20. Ali N, AlAsmari AF, Imam F, et al. Protective effect of diosmin against doxorubicin-induced nephrotoxicity. Saudi J Biol Sci. 2021;28(8):4375-4383. doi:10.1016/j.sjbs.2021.04.030
Referans21. Srinivasan S, Pari L. Ameliorative effect of diosmin, a citrus flavonoid against streptozotocin-nicotinamide generated oxidative stress induced diabetic rats. Chem Biol Interact. 2012;195(1):43-51. doi:10.1016/j.cbi.2011.10.003
Referans22. Ahmed S, Mundhe N, Borgohain M, et al. Diosmin Modulates the NF-kB Signal Transduction Pathways and Downregulation of Various Oxidative Stress Markers in Alloxan-Induced Diabetic Nephropathy. Inflammation. 2016;39(5):1783-1797. doi:10.1007/s10753-016-0413-4
Referans23. Bedoschi G, Navarro PA, Oktay K. Chemotherapy-induced damage to ovary: mechanisms and clinical impact. Future Oncol. 2016;12(20):2333-2344. doi:10.2217/fon-2016-0176
Referans24. Moolhuijsen LME, Visser JA. Anti-Müllerian Hormone and Ovarian Reserve: Update on Assessing Ovarian Function. J Clin Endocrinol Metab. 2020;105(11):3361-3373. doi:10.1210/clinem/dgaa513
Referans25. Findlay JK, Hutt KJ, Hickey M, Anderson RA. How Is the Number of Primordial Follicles in the Ovarian Reserve Established?. Biol Reprod. 2015;93(5):111. doi:10.1095/biolreprod.115.133652
Referans26. Calis P, Bozdag G, Karakoc Sokmensuer L, Kender N. Does ischemia-reperfusion injury affect ovarian reserve and follicle viability in a rat model with adnexal torsion?. Eur J Obstet Gynecol Reprod Biol. 2015;185:126-130. doi:10.1016/j.ejogrb.2014.12.006