Doksorubisin ile İndüklenmiş Ovaryan Toksisitede Visnaginin Koruyucu Etkisi

Abstract

Doksorubisine bağlı ovaryan toksisitede ovaryan rezervi korumak amacıyla farklı tedavi yaklaşımları uygulanmaktadır. Visnagin doksorubisine bağlı kardiyotoksisitede tedavi edici etkinliği gösterilmiş organik bir kimyasaldır.  Bununla birlikte doksorubisine bağlı ovaryan toksisitede visnaginin etkinliği bilinmemektedir. Doksorubisine bağlı ovaryan toksisitenin oluşturulduğu sıçanlarda visnaginin tedavi edici etkinliğini değerlendiren bu çalışmada; doksorubisinin ovaryan rezervi belirleyen primordiyal follikül sayısını, bunun yanında preantral ve antral follikül sayısını azalttığı saptandı. İntraperitoneal 30 mg/kg visnagin tedavisinin primordiyal follikül rezervini, gelişmekte olan ve olgun follikül sayılarını koruduğu, atretik follikül sayısını azalttığı görüldü. Doksorubisin ile indüklenmiş ovaryan toksisitenin visnagin tedavisi ile azaltıldığı ve ovaryan follikül rezervini koruduğu sonucuna varıldı.

Keywords

• Doksorubisin,Visnagin,Ovaryan Toksisite

Protective Effect of Visnagin on Doxorubicin-Induced Ovarian Toxicity

Abstract

Different treatment approaches are used to for preserve ovarian reserve in ovarian toxicity due to doxorubicin. Visnagin is an organic chemical that shows therapeutic activity on doxorubicin-induced cardiotoxicity. However, the efficacy of visnagin on ovarian toxicity due to doxorubicin is unknown. In this study evaluating the therapeutic effect of visnagin in rats with ovarian toxicity induced by doxorubicin, it was determined that doxorubicin decreased the number of primordial follicles that determined ovarian reserve, as well as the number of preantral and antral follicles. Intraperitoneal administration of 30 mg/kg of visnagin treatment decreased the number of atretic follicles and preserved primordial, developing and mature follicle counts. As a result, it was concluded that ovarian toxicity induced by doxorubicin was reduced with visnagin treatment and the visnagin treatment preserved of ovarian follicle reserve.

Keywords

• Doxorubicin,Visnagin,Ovarian toxicity

References

1. Monsuez J.-J, Charniot J.-C, Vignat N, & Artigou J.-Y Cardiac side-effects of cancer chemotherapy. International Journal of Cardiology 2010; 144(1), 3–15.
2. Van Dyke T. p53 and tumor suppression. The New England Journal of Medicine, 2007; 356(1), 79–81.
3. Bar-Joseph H, Ben-Aharon I, Rizel S, Stemmer SM, Tzabari M, et al. Doxorubicin-induced apoptosis in germinal vesicle (GV) oocytes. Reproductive Toxicology 2010;30: 566–572.
4. Liu Y, Asnani A, Zou L, Bentley V. L, Yu M, Wang Y, Peterson R. T Visnagin protects against doxorubicin-induced cardiomyopathy through inhibtion of mitochondrial malate dehydrogenase. 2014; 6(266): 266ra170.
5. Duarte J, Torres A. I, Zarzuelo A Cardiovascular effects of visnagin on rats. Planta Med. 2000; 66, 35-39.
6. Vanachayangkul P, Byer K, Khan S, Butterweck V. An aqueous extract of Ammi visnaga fruits and its constituents khellin and visnagin prevent cell damage caused by oxalate in renal epithelial cells. Phytomedicine, 2010;17, 653-658.
7. Ross MH, Pawlina W. Histology A Text And Atlas with Corralated Cell and Molacular Biology. 6th edition ed. Vol. LWW. 833-837, 2011.
8. Garrett W M, Guthrie H. D Expression of Androgen Receptors and Steroidogenic Enzymes in Relation to Follicular Growth and Atresia Following Ovulation in Pigs, Biology of Reproduction, 1996; 55, 949-55.

9. Ben-Aharon I, Bar-Joseph H, Tzarfaty G, Kuchinsky L, Rizel S, Stemmer SM, Shalgi R Doxorubicin-induced ovarian toxicity. Reprod Biol Endocrinol. 2010; 8:20.
10. McLaughlin M, Kelsey T.W, Wallace W.H.B, Anderson R.A, Telfer E.E Non-growing follicle density is increased following adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) chemoterapy in the adult human ovary. Human Reproduction. Vol.32, No. I pp. 2017; 165-174.
11. Oktay K, Oktem O, Reh A, Vahdat L Measuring the impact of chemotherapy on fertility in women with breast cance. J Clin Oncol. 2006; 24:4044-4046.
12. Agarwal A, Gupta, S, Sharma R.K, Role of oxidative stress in female reproduction. Reprod. Biol. Endocrinol. 2005; 3, 28.
13. Chow AY, Chin C, Dahl G, Rosenthal DN Anthracyclines cause endothelial injury in pediatric cancer patients: a pilot study. J Clin Oncol. 2006; 24:925-928.
14. Wu S, Ko YS, Teng MS, Ko YL, Hsu LA, Hsueh C, Chou YY, Liew CC, Lee YS Adriamycin-induced cardiomyocyte and endothelial cell apoptosis: in vitro and in vivo studies. J Mol Cell Cardiol. 2002; 34:1595-1607.
15. Zhang T, He W.N, Feng L.L, Huang H.G Effect Of Doxorubicin-İnduced Ovarian Toxicity On Mouse Ovarian Granulosa Cells. Regulatory Toxicology And Pharmacology 2017; 86 1e10.
16. Isobe N, Yoshimura Y Localization of apoptotic cells in the cystic ovarian follicles of cows: a DNA-end labeling histochemical study. Theriogenology. 2000; 53, 897–904.
17. Slot K, Voorendt M, Boer-Brouwer M, Vugt H, Teerds K Estrous cycle dependent changes in expression and distribution of Fas, Fas ligand, Bcl-2, Bax, and pro- and active caspase-3 in the rat ovary. Journal of Endocrinology. 2006; 188:179–192.
18. Vaskivuo TE, Anttonen M, Herva R, Billig H, Dorland M, Te Velde ER, Stenback H, Heikinheimo M, Tapanainen JS Survival of human ovarian follicles from fetal to adult life: apoptosis, apoptosis-related proteins, and transcription factor GATA-4. J Clin Endocrinol Metab. 2001; 86:3421–3429.
19. Glamoclija V, Vilovic K, Saraga-Babic M, Baranovic A, Sapunar D Apoptosis and active caspase-3 expression in human granulosa cells. Fertil Steril. 2005; 83:426–431.
20. Gewirtz D.A, A critical evaluation of the mechanisms of action proposed for the antitumor effects of the anthracycline antibiotics adriamycin and daunorubicin. Biochem. Pharmacol. 1999; 57, 727e741.
21. Attia, S.M, Al-Bakheet, S.A, Al-Rasheed, N.M Proanthocyanidins produce significant attenuation of doxorubicin-induced mutagenicity via suppression of oxidative stress. Oxid. Med. Cell. Longev. 2010; 3, 404e413.
22. Yeh Y.C, Liu T.J, Wang L.C, Lee H.W, Ting C.T, Lee W.L, Hung C.J, Wang K.Y, Lai H.C, Lai H.C, A standardized extract of Ginkgo biloba suppresses doxorubicin-induced oxidative stress and p53-mediated mitochondrial apoptosis in rat testes. Br. J. Pharmacol. 2009; 156, 48e61.
23. Roti Roti, E.C, Salih, S.M, Dexrazoxane ameliorates doxorubicin-induced injury in mouse ovarian cells. Biol. Reprod. 2012; 86, 96.
24. Roti Roti EC, Ringelstetter AK, Kropp J, Abbott DH, Salih SM Bortezomib Prevents Acute Doxorubicin Ovarian Insult and Follicle Demise, Improving the Fertility Window and Pup Birth Weight in Mice. PLoSONE9 2014; (9): e 108174.
25. Elon C, Roti Roti, M. Salih Dexrazoxane Ameliorates Doxorubicin-Induced Injury in Mouse Ovarian Cells. Bıology Of Reproductıon 2012; 86(3):96,1–11.
26. Lee J.K, Jung J.S, Park S.H, Park S.H, Sim Y.B, Kim S.M, Han T.S, Suh H.W Anti-inflammatory Effect of Visnagin in Lipopolysaccharide-stimulated BV-2 Microglial Cells. Arch Pharm Res Vol 33, No: 11, 2010; 1843-1850.
27. Kwon M.S, Lee J.K, Park S.H, Sim Y.B, Jung J.S, Won M.H, Kim S.M, Suh H.W Neuroprotective Effect of Visnagin on Kainic Acid-induced Neuronal Cell Death in the Mice Hippocampus Korean J Physiol Pharmacol Vol 14. 2010; 257－263.
28. Duarte J, Perez-Vizcaino F, Torres AI, Zarzuelo A, Jimenez J, Tamargo J Vasodilator effects of visnagin in isolated rat vascular smooth muscle. Eur J Pharmacol. 1995; 286:115-122.
29. Vanachayangkul P, Chow N, Khan SR, Butterweck V Prevention of renal crystal deposition by an extract of Ammi visnaga L. and its constituents khellin and visnagin in hyperoxaluric rats. Urol Res 39: 2011;189-195.
30. Hassan Y, Aboul-Eneın, Kladna A, Kruk I, Lıchszteld K, Mıchalska T Effect of Psoralens on Fenton-Like Reaction Generating Reactive Oxygen Species. Biopolymers (Biospectroscopy), 2003; Vol. 72, 59–68.
31. Zhang JG, Viale M, Esposito M, Lindup WE Tiopronin protects against the nephrotoxicity of sisplatin in the rat. Hum Exp Toxicol. 1999; 18(12):713-7.
32. Abalo R, Cabezos PA, Vera G, López-Pérez AE, Martín MI Cannabinoids may worsen gastric dysmotility induced by chronic cisplatin in the rat. Neurogastroenterol Motil. 2013; 25(5):373-82.