Esra ŞEN, Seda SARIBAL SAYGI, Aysun ÖNAL, Ayşe AKBAŞ, Berrin AVCI, Zeynep KAHVECİ

Sıçan Ovaryum Dokusunda Doksorubisin ile İndüklenmiş Folliküler Apoptotik Aktivasyonda Dialil Disülfit’in Koruyucu Etkisi

Bu çalışmada önemli bir kemoterapötik ajan olan doksorubisinin ovaryum üzerindeki toksisitesini belirlemek ve ovaryan toksisite üzerine yüksek antioksidan kapasiteye sahip olan dialil disülfitin etkinliğini değerlendirmek amaçlandı. Çalışma kapsamında 35 adet Wistar albino cinsi dişi sıçan 5 alt gruba ayrıldı: Grup I: Kontrol-Doksorubisin Grubu, Grup II: Kontrol-Dialil disülfit Grubu, Grup III: Doksorubisin Uygulanan Grup, Grup IV: Dialil disülfit Uygulanan Grup, Grup V: Doksorubisin + Dialil disülfit Uygulanan Grup. Morfolojik değerlendir-me hematoksilen eozin boyaması ile gerçekleştirildi. Apoptotik aktivasyon TUNEL yöntemi ile değerlendirildi. Doksorubisin uygulamasının primordiyal, sekonder ve graaf follikül sayılarında azalmaya sebep olduğu gözlemlenirken, atretik follikül sayılarını ise arttırdığı saptandı. Dialil disülfit tedavisinin doksorubisin ile indüklenmiş ovaryan toksisiteyi azaltabileceği ve ovaryan follikül rezervinin korunmasında etkili olabileceği sonucuna varıldı.

Anahtar Kelimeler:

apoptoz, Dialil disülfit, Doksorubisin

Effect of Diallyl Disulfide on Doxorubicin-induced Follicular Apoptotic Activation in Rat Ovarian Tissue

The aim of this study was to determine the toxicity of doxorubicin, an important chemotherapeutic agent, on the ovary and to evaluate the efficacy of dialyl disulfide which has high antioxidant capacity on ovarian toxicity. In this study, 35 female Wistar albino rats were divided into 5 subgroups: Group I: Control-Doxorubicin Group, Group II: Control-Dialyl disulfide Group, Group III: Doxorubicin Applied Group, Group IV: Diallyl disulfide Applied Group, Group V: Doxorubicin + Diallyl disulfide Group. Morphological evaluation was performed with hematoxylin eosin staining. Apoptotic activation was evaluated by TUNEL method. Doxorubicin caused a decrease in the number of primor-dial, secondary and graaf follicles, and increased atretic follicle counts. It was concluded that dialyl disulfide treatment may reduce doxoru-bicin-induced ovarian toxicity and may be effective in maintaining ovarian follicular reserve.

PDF

___

Mohan P, Rapoport N. Doxorubicin as a Molecular Nanotheranostic Agent: Effect of Doxorubicin Encapsulation in Micelles or Nanoemulsions on the Ultrasound-Mediated Intracellular Delivery and Nuclear Trafficking. Mol Pharm. 2010;7(6):1959-73.
Arcamone F, Cassinelli G, Fantini G et al. Adriamycin, 14-Hydroxydaunomycin, a new antitumor antibiotic from S. peucetius var. caesius. Biotechnol Bioeng. 2000;67(6):704-13.
Bendale Y, Bendale V, Paul S. Evaluation of cytotoxic activity of platinum nanoparticles against normal and cancer cells and its anticancer potential through induction of apoptosis. Integr Med Res. 2017;6(2):141-48.
Vallejo MJ, Salazar L, Grijalva M. Oxidative Stress Modulation and ROS-Mediated Toxicity in Cancer: A Review on In Vitro Models for Plant-Derived Compounds. Oxidative Medicine and Cellular Longevity. 2017;doi:10.1155/2017/4586068.
Louis J, Limarzi LR, Best WR. Treatment of Chronic Granulocytic Leukemia with Myleran. A.M.A Archives of Internal Medicine. 1957;97(3):299-08.
Falcone T, Attaran M, Bedaiwy MA, Goldberg JM. Ovarian Function Preservation in the Cancer Patient. Fertil Steril. 2004;81(2):243-57.
Blumenfeld Zeev. Chemotherapy and Fertility. Best Pract Res Clin Obstet Gynaecol. 2012;26(3):379-90.
Irving-Rodgers HF, Krupa M, Rodgers RJ. Cholesterol Side-Chain Cleavage Cytochrome P450 and 3β-Hydroxysteroid Dehydrogenase Expression and the Concentrations of Steroid Hormones in the Follicular Fluids of Different Phenotypes of Healthy and Atretic Bovine Ovarian Follicles. Biol Reprod. 2004;69(6):2022-28.
Adaki S, R Adaki, K Shah, Karagir A. Garlic: Review of Literature. Indian J Cancer. 2014;51(4):577-81.
Pedraza-Chaverrí J, González-Orozco AE, Maldonado PD, Barrera D, Medina-Campos ON, Hernández-Pando R. Diallyl Disulfide Ameliorates Gentamicin-Induced Oxidative Stress and Nephropathy in Rats. Eur J Pharmacol. 2003;473(1):71-78.
Ross MH, Pawlina W. Histology A Text And Atlas with Corralated Cell and Molacular Biology. 6th edition. LWW. 2011. 833-837.
Losa M, Barzaghi RL, Mortini P, Franzin A, Mangili F, Terreni MR, Giovanelli M. Determination of the Proliferation and Apoptotic Index in Adrenocorticotropin-Secreting Pituitary Tumors Comparison between Micro- and Macroadenomas. Am J Pathol. 2000;156(1):245-51.
Maltaris T, Seufert R, Fischl F et al. The Effect of Cancer Treatment on Female Fertility and Strategies for Preserving Fertility. Eur J Obstet Gynecol Reprod Biol. 2007; 130(2):148-55.
Oktem O, Oktay K. A Novel Ovarian Xenografting Model to Characterize the Impact of Chemotherapy Agents on Human Primordial Follicle Reserve. Cancer Res. 2007;67(21):10159-62.
Oktay K, Sönmezer M. Chemotherapy and Amenorrhea: Risks and Treatment Options. Curr Opin Obstet Gynecol. 2008;20(4):408-15.
Lass A. Assessment of Ovarian Reserve. Is There Still a Role for Ovarian Biopsy in the Light of New Data?. Hum Reprod. 2004;19(3):467-69.
La Ferla B, Airoldi C, Zona C et al. Natural Glycoconjugates with Antitumor Activity. Nat. Prod. Rep. 2011;28(3):630-48.
Thorn CF, Oshiro C, Marsh S et al. (2011) Doxorubicin Pathways: Pharmacodynamics and Adverse Effects. Pharmacogenet Genom. 2011;21(7):440-46.
Xiao S, Zhang J, Liu M, Iwahata H, Rogers HB, Woodruff TK. Doxorubicin Has Dose-Dependent Toxicity on Mouse Ovarian Follicle Development, Hormone Secretion, and Oocyte Maturation. Toxicol Sci. 2017;157(2):320-29.
Xiao S, Zhang J, Liu M, Iwahata H, Rogers HB, Woodruff TK. Doxorubicin Has Dose-Dependent Toxicity on Mouse Ovarian Follicle Development, Hormone Secretion, and Oocyte Maturation. Toxicol Sci. 2017;157(2):320-29.
Yucebilgin MS, Terek MC, Ozsaran A et al. Effect of Chemotherapy on Primordial Follicular Reserve of Rat: An Animal Model of Premature Ovarian Failure and Infertility. Aust Nz J Obstet Gyn. 2004;44(1):6-9.
Roti Roti, E.C, Salih, S.M. Dexrazoxane ameliorates doxorubicin-induced injury in mouse ovarian cells. Biol Reprod. 2012;86(3):96.
Blumenfeld Z. How to Preserve Fertility in Young Women Exposed to Chemotherapy? The Role of GnRH Agonist Cotreatment in Addition to Cryopreservation of Embrya, Oocytes, or Ovaries. Oncologist. 2007;12(9):1044-54.
Block E. The Chemistry of Garlic and Onions. Sci Am. 1985;252(3):114-19.