Brusatol Over İskemi Reperfüzyonu ile İndüklenmiş Over Dokusu Oksidatif Yaralanmasını Azaltır

Yıl 2021, Cilt: 7 Sayı: 2, 206 - 211, 12.07.2021

Fazile Nur Ekinci Akdemir , Ayhan Tanyeli , Mustafa Can Güler , Ersen Eraslan , Emsal Pınar Topdağı Yılmaz , Yunus Emre Topdağı

https://doi.org/10.53394/akd.959254

Cited By: 2

Öz

Objective: In the scope of this study, it was tried to examine the probable benefits of brusatol against
ovarian tissue injury originating from bilateral ovarian torsion/detorsion (T/D).
Material and Methods: In this study, experimental animals were randomized to 4 groups. Groups
were programmed as sham group I (control), group II (T/D), group III (DMSO+T/D) and group
IV (Brusatol+T/D). Group I; the abdomen region was barbered, disinfected, opened by incision and
closed respectively, but no T/D model was performed. Group II, as described in group I, after opening
and closing abdominal incision, 3 hours of torsion was applied and it was followed by a 3-hour of
detorsion. Group III, 1% DMSO was applied intraperitoneally 0,3 ml as every other day for 10
days and the last dose was given 30 minutes prior to detorsion. Group IV; brusatol was administered
intraperitoneally 0,5 mg/ml once every 2 days for 10 days and the last dose was applied 30 minutes
prior to detorsion. Then, all processes were carried out as described in group II. Following detorsion
period, in pursuit of sacrificing the rats, ovarian tissues were removed.
Results: Oxidant parameters (MDA, MPO, TOS, OSI) and pro-inflammatory cytokine (TNF-α,
IL-1β) levels increased significantly while antioxidant levels (SOD, TAS) reduced in group II and III
compared to group I (p<0.05). On the contrary, brusatol application (group IV) reversed all of these
values compared to group II and III (p<0.05).
Conclusion: As a conclusion, brusatol was evaluated to have protective effects against T/D-induced
ovarian injury in rats.

Anahtar Kelimeler

Brusatol, Ovary, Torsion-Detorsion, Ischemia Reperfusion, Rat

Brusatol Over İskemi Reperfüzyonu ile İndüklenmiş Over Dokusu Oksidatif Yaralanmasını Azaltır

Öz

Amaç: Bu çalışmanın kapsamında bilateral over torsiyon/detorsiyonundan (T/D) kaynaklanan over
dokusu yaralanmasına karşı brusatolün olası yararları araştırılmaya çalışıldı.
Gereç ve Yöntemler: Bu çalışmada deney hayvanları 4 gruba randomize edildi. Gruplar grup
I (sham-kontrol), grup II (T/D), grup III (DMSO+T/D) ve grup IV (Brusatol+T/D) olarak
programlandı. Grup I; karın bölgesi traşlanıp, dezenfekte edildi, kesi ile açıldı ve tekrar kapatıldı,
ancak T/D modeli uygulanmadı. Grup II'de, grup I'de tarif edildiği gibi, abdominal insizyon
yapıldıktan sonra 3 saat torsiyon uygulandı ve bunu 3 saatlik detorsiyon izledi. Grup III, %1 DMSO,
10 gün boyunca her gün olduğu gibi intraperitonal olarak 0,3 ml uygulandı ve son doz detorsiyondan
30 dakika önce uygulandı. Daha sonra, tüm işlemler grup II' de tarif edildiği gibi gerçekleştirildi.
Grup IV; brusatol, 10 gün boyunca her 2 günde bir 0,5 mg/ml intraperitonal olarak uygulandı ve
detorsiyondan 30 dakika önce son dozu verildi. Detorsiyon süresinin ardından sıçanların sakrifiye
edilerek over dokuları çıkarıldı.
Bulgular: Grup II ve III' te grup I ile karşılaştırıldığında, oksidan parametreler (MDA, MPO,
TOS, OSI) ve proinflamatuar sitokin (TNF-α, IL-1β) düzeyleri artarken, antioksidan (SOD, TAS)
parametreler önemli ölçüde azaldı (p<0.05). Aksine, brusatol uygulaması (grup IV), grup II ve III' e
kıyasla bu değerlerin hepsini tersine çevirdi (p<0.05).
Sonuç: Sonuç olarak, brusatol’ ün sıçanlarda T/D kaynaklı over hasarına karşı koruyucu etkileri
olduğu değerlendirildi.

Anahtar Kelimeler

Brusatol, Over, Torsiyon-Detorsiyon, İskemi Reperfüzyon, Sıçan

Kaynakça

• 1. Hibbard LT. Adnexal torsion. Am J Obstet Gynecol 1985; 152(4): 456-61.
• 2. Houry D, Abbott JT. Ovarian torsion: a fifteen-year review. Ann Emerg Med 2001;38(2):156-9.
• 3. Tuncer AA, Bozkurt MF, Koken T, Dogan N, Pektaş MK, Baskin Embleton D. The Protective Effects of Alpha-Lipoic Acid and Coenzyme Q10 Combination on Ovarian Ischemia-Reperfusion Injury: An Experimental Study. Adv Med 2016; 2016: 3415046.
• 4. Mashiach S, Bider D, Moran O, Goldenberg M, Ben-Rafael Z. Adnexal torsion of hyperstimulated ovaries in pregnancies after gonadotropin therapy. Fertil Steril 1990;53(1): 76-80.
• 5. Yuk JS, Kim LY, Shin JY, Choi DY, Kim TY, Lee JH. A national population-based study of the incidence of adnexal torsion in the Republic of Korea. International journal of gynaecology and obstetrics: the official organ of the Int Fed Gynaecol Obstet 2015; 129(2): 169-70.
• 6. Sengul O, Ferah I, Polat B, Halici Z, Bayir Y, Yilmaz M, Kilic N, Keles ON. Blockade of endothelin receptors with bosentan limits ischaemia/reperfusion-induced injury in rat ovaries. Eur J Obstet Gynecol Reproduc Biol 2013; 170(2): 458-63
• 7. Park ES, Kim J, Ha TU, Choi JS, Hong KS, Rho J TDAG51 deficiency promotes oxidative stress-induced apoptosis through the generation of reactive oxygen species in mouse embryonic fibroblasts. Experimental & molecular medicine. 2013; 45: 35.
• 8. Kohen R, Nyska A. Oxidation of biological systems: oxidative stress phenomena, antioxidants, redox reactions, and methods for their quantification. Toxicol Pathol 2002; 30(6): 620-50.
• 9. Girotti AW. Lipid hydroperoxide generation, turnover, and effector action in biological systems. J Lipid Res 1998; 39(8): 1529-42.
• 10. Feillet-Coudray C, Rock E, Coudray C, Grzelkowska K, Azais-Braesco V, Dardevet D, Mazur A. Lipid peroxidation and antioxidant status in experimental diabetes. Clinica chimica acta; Int J Clin Chem 1999; 284(1): 31-43.
• 11. Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem 2005; 38(12): 1103-11.
• 12. Bozkurt S, Arikan DC, Kurutas EB, Sayar H, Okumus M, Coskun A, Bakan V. Selenium has a protective effect on ischemia/reperfusion injury in a rat ovary model: biochemical and histopathologic evaluation. J Pediatr Surg 2012; 47(9): 1735-41.
• 13. Carden DL, Granger DN. Pathophysiology of ischaemia- reperfusion injury. J Pathol 2000; 190(3): 255-66. 14. Filho DW, Torres MA, Bordin AL, Crezcynski-PasaTB, Boveris A. Spermatic cord torsion, reactive oxygen and nitrogen species and ischemia-reperfusion injury. Mol Aspects Med 2004; 25(1-2): 199-210.
• 15. Eltzschig HK, Collard CD. Vascular ischaemia and reperfusion injury. Br Med Bull 2004; 70: 71-86.
• 16. Dinarello CA. Proinflammatory cytokines. Chest 2000; 118(2): 503-8.
• 17. Van Antwerpen P, Boudjeltia KZ, Babar S, Legssyer I, Moreau P, Moguilevsky N, Vanhaeverbeek M, Ducobu J, Nève J. Thiol-containing molecules interact with the myeloperoxidase/H2O2/chloride system to inhibit LDL oxidation. Biochem Biophys Res Com 2005; 337(1): 82-8.
• 18. Hasiakos D, Papakonstantinou K, Kontoravdis A, GogasL, Aravantinos L, Vitoratos N. Adnexal torsion during pregnancy: report of four cases and review of the literature. J Obstet Gynaecolo Res 2008; 34(4 Pt 2): 683-7.
• 19. Tang W, Xie J, Xu S, Lv H, Lin M, Yuan S, Bai J, Hou Q , Yu S. Novel nitric oxide-releasing derivatives of brusatol as anti-inflammatory agents: design, synthesis, biological evaluation, and nitric oxide release studies. J Med Chem 2014; 57(18): 7600-12.
• 20. Liu JH, Qin JJ, Jin HZ, Hu XJ, Chen M, Shen YH, Yan SK, Zhang WD. A new triterpenoid from Brucea javanica. Arch Pharm Res 2009; 32(5): 661-6.
• 21. Ali FF, Ahmed, AF, Elroby Ali DM. Underlying mechanisms behind the protective effect of angiotensin (1–7) in experimental rat model of ovarian ischemia reperfusion injury. Life Sci 2019; 235: 116840.
• 22. Zhou J, Wang T, Dou Y, Huang Y, Qu C, Gao J, Huang Z, Xie Y, Huang P, Lin Z, Su Z. Brusatol ameliorates 2, 4, 6-trinitrobenzenesulfonic acid-induced experimental colitis in rats: Involvement of NF-κB pathway and NLRP3 inflammasome. Int immunopharmacol. 2018; 64: 264- 274 . 23. Ohkawa H, Ohishi N, Yagi K. Assay for Lipid Peroxides in Animal-Tissues by Thiobarbituric Acid Reaction. Anal Biochem 1979; 95(2): 351-8.
• 24. Sun Y, Oberley LW, Li Y. A Simple Method for Clinical Assay of Superoxide-Dismutase. Clin Chem 1988; 34(3): 497-500.
• 25. Bradley PP, Priebat DA, Christensen RD, Rothstein G. Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. J Invest Dermatol 1982; 78(3): 206-9.
• 26. Demiryilmaz I, Sener E, Cetin N, Akcay F, Suleyman H. A comparative investigation of biochemical and histopathological effects of thiamine and thiamine pyrophosphate on ischemia-reperfusion induced oxidative damage in rat ovarian tissue. Arch Pharm Res 2013;36(9):1133-9.
• 27. Cohen SB, Oelsner G, Seidman DS, Admon D, Mashiach S, Goldenberg M. Laparoscopic detorsion allows sparing of the twisted ischemic adnexa. The Journal of the Am Assoc Gynecol Lap 1999; 6(2): 139-43.
• 28. Yapca OE, Turan MI, Cetin N, Borekci B, Gul MA. Use of thiamine pyrophosphate to prevent infertility developing in rats undergoing unilateral ovariectomy and with ischemia reperfusion induced in the contralateral ovary. Eur J Obstet Gynecol Reproduc Biol 2013; 170(2): 521-5.
• 29. Yigiter M, Halici Z, Odabasoglu F, Keles ON, Atalay F, Unal B, Salman AB. Growth hormone reduces tissue damage in rat ovaries subjected to torsion and detorsion: biochemical and histopathologic evaluation. Eur J Obstet Gynecol Reproduc Biol 2011; 157(1): 94-100.
• 30. Zhang Y, Zhu J, Guo L, Zou Y, Wang F, Shao H, Li J, Deng X. Cholecystokinin protects mouse liver against ischemia and reperfusion injury. Int immunopharmacol 2017; 48: 180-6.
• 31. Takada M, Nadeau KC, Shaw GD, Marquette KA, Tilney NL. The cytokine-adhesion molecule cascade in ischemia/reperfusion injury of the rat kidney. Inhibition by a soluble P-selectin ligand. J Clin Invest 1997; 99(11): 2682-90.
• 32. Daemen MA, van ‘t Veer C, Denecker G, Heemskerk VH, Wolfs TG, Clauss M, Vandenabeele P, Buurman WA. Inhibition of apoptosis induced by ischemia-reperfusion prevents inflammation. J Clin Invest 1999; 104(5): 541-9. 33. Liu X, Xu H, Zhang Y, Wang P, Gao W. Brusatol inhibits amyloid-beta-induced neurotoxicity in U-251 cells via regulating the Nrf2/HO-1 pathway. Journal of cellular biochemistry. 2019;120(6):10556-63.
• 34. Zhou J, Wang T, Dou Y, Huang Y, Qu C, Gao J, HuangZ, Xie Y, Huang P, Lin Z, Su Z.Brusatol ameliorates 2, 4, 6-trinitrobenzenesulfonic acid-induced experimental colitis in rats: Involvement of NF-kappaB pathway and NLRP3 inflammasome. Int immunopharmacol 2018; 64:264-74.
• 35. Turpaev K, Krizhanovskii C, Wang X, Sargsyan E, Bergsten P, Welsh N. The protein synthesis inhibitor brusatol normalizes high-fat diet-induced glucose intolerance in male C57BL/6 mice: role of translation factor eIF5A hypusination. FASEB J 2019; 33(3): 3510-22.
• 36. Evans JP, Winiarski BK, Sutton PA, Jones RP, Ressel L, Duckworth CA, Pritchard DM, Lin ZX, Fretwell VL, Tweedle EM, Costello E, Goldring CE, Copple IM, Park BK, Palmer DH, Kitteringham NR. Correction: The Nrf2 inhibitor brusatol is a potent antitumour agent in an orthotopic mouse model of colorectal cancer. Oncotarget 2019; 10(6): 685.