ANTI-OXIDATIVE PROTECTION OF VITAMIN E AGAINST DOXORUBICIN INDUCED OVARIAN TOXICITY IN ANIMAL MODEL
DOI:
https://doi.org/10.69656/pjp.v20i2.1635Keywords:
Vitamin E, Antioxidant, Ovarian toxicity, Chemotherapy, DoxorubicinAbstract
Background: Chemotherapy has diverse pathologic consequences on the female reproductive system. Current study aimed to ascertain whether vitamin-E administration shielded female rats against doxorubicin-induced ovarian damage. Methods: This laboratory experimental study was conducted at the Department of Anatomy, Khyber Medical University, Peshawar. In this study, 24 female rats weighing between 200 and 250 gm were used and divided into three groups, the control group, research group-I, and research group-II. All animals got weighed at the start of the study and again prior to their sacrifice. On the 28th day, animals were sacrificed, and organs were taken out. To observe any change in the ovarian follicles, 5 um thick sections were cut on a rotary microtome and stained with Hematoxylin and Eosin (H&E) and Massan Trichome. The SPSS-25 was used to analyse the data. The difference between and within groups was measured using the independent sample t-test and chi square test. p?0.05 was considered statistically significant. Results: Rats in both the control and experimental groups-II showed a substantial rise in mean weight (p<0.05), however rats in experimental group-I showed a significant drop in mean body weight (p>0.05) after the experiments. The number of primordial and secondary ovarian follicles did not differ significantly across groups (p>0.05), however there was a significant difference in the number of primary ovarian follicles, atretic follicles, and nuclear fragments (p<0.05). Conclusion: In female rats, simultaneous administration of vitamin E has demonstrated protective effects against doxorubicin-induced ovarian damage.
Pak J Physiol 2024;20(2):41-5
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Kim J, Park EY, Kim O, Schilder JM, Coffey DM, Cho CH, et al. Cell origins of high-grade serous ovarian cancer. Cancers (Basel) 2018;10(11):433.
Partridge AH, Ruddy KJ, Gelber S, Schapira L, Abusief M, Meyer M, et al. Ovarian reserve in women who remain premenopausal after chemotherapy for early stage breast cancer. Fertil Steril 2010;94(2):638–44.
Morgan S, Anderson RA, Gourley C, Wallace WH, Spears N. How do chemotherapeutic agents damage the ovary? Hum Reprod Update 2012;18(5):525–35.
Bedoschi G, Navarro PA, Oktay K. Chemotherapy-induced damage to ovary: mechanisms and clinical impact. Future Oncol 2016;12(19):2333–44.
Lambertini M, Ginsburg ES, Partridge AH. Update on fertility preservation in young women undergoing breast cancer and ovarian cancer therapy. Curr Opin Obstet Gynecol 2015;27(1):98–107.
Tacar O, Sriamornsak P, Dass CR. Doxorubicin: an update on anticancer molecular action, toxicity and novel drug delivery systems. J Pharm Pharmacol 2013;65(2):157–70.
Pusapati RV, Rounbehler RJ, Hong S, Powers JT, Yan M, Kiguchi K, et al. ATM promotes apoptosis and suppresses tumorigenesis in response to Myc. Proc Nat Acad Sci USA 2006;103(5):1446–51.
Kerr J, Brogan L, Myers M, Hutt K, Mladenovska T, Ricardo S, et al. The primordial follicle reserve is not renewed after chemical or ?-irradiation mediated depletion. Reproduction 2012;143(4):469–76.
Estaquier J, Vallette F, Vayssiere J-L, Mignotte B. The mitochondrial pathways of apoptosis. Adv Exp Med Biol 2012;942:157–83.
Galli F, Azzi A, Birringer M, Cook-Mills JM, Eggersdorfer M, Frank J, et al. Vitamin E: Emerging aspects and new directions. Free Radic Biol Med 2017;102:16–36.
Miyazawa T, Burdeos GC, Itaya M, Nakagawa K, Miyazawa T. Vitamin E: regulatory redox interactions. IUBMB life 2019;71(4):430–41.
Swamy AV, Gulliaya S, Thippeswamy A, Koti BC, Manjula DV. Cardioprotective effect of curcumin against doxorubicin-induced myocardial toxicity in albino rats. Indian J Pharmacol 2012;44(1):73–7.
Azman A, Khalid B, Ima-Nirwana S. The effects of vitamin E on bodyweight and fat mass in intact and ovariectomized female rats. Med J Islamic World Acad Sci 2001;14(4):125–38.
Morgan S, Lopes F, Gourley C, Anderson RA, Spears N. Cisplatin and doxorubicin induce distinct mechanisms of ovarian follicle loss; imatinib provides selective protection only against cisplatin. PloS One 2013;8(7):e70117.
Bar-Joseph H, Ben-Aharon I, Rizel S, Stemmer SM, Tzabari M, Shalgi R. Doxorubicin-induced apoptosis in germinal vesicle (GV) oocytes. Reprod Toxicol 2010;30(4):566–72.
Zhang T, He WH, Feng LL, Huang HG. Effect of doxorubicin-induced ovarian toxicity on mouse ovarian granulosa cells. Regul Toxicol Pharmacol 2017;86:1–10.
Brayboy LM, Oulhen N, Long S, Voigt N, Raker C, Wessel GM. Multidrug resistance transporter-1 and breast cancer resistance protein protect against ovarian toxicity, and are essential in ovarian physiology. Reprod Toxicol 2017;69:121–31.
Al-Kawlani B, Murrieta-Coxca JM, Chaiwangyen W, Fröhlich K, Fritzsche A, Winkler S, et al. Doxorubicin induces cytotoxicity and miR-132 expression in granulosa cells. Reprod Toxicol 2020;96:95–101.
Renu K, Pureti LP, Vellingiri B, Valsala Gopalakrishnan A. Toxic effects and molecular mechanism of doxorubicin on different organs–an update. Toxin Rev 2022;41(2):650–74.
Samare-Najaf M, Zal F, Safari S. Primary and secondary markers of doxorubicin-induced female infertility and the alleviative properties of quercetin and vitamin E in a rat model. Reprod Toxicol 2020;96:316–26.
Granados-Principal S, Quiles JL, Ramirez-Tortosa CL, Sanchez-Rovira P, Ramirez-Tortosa M. New advances in molecular mechanisms and the prevention of adriamycin toxicity by antioxidant nutrients. Food Chem Toxicol 2010;48(6):1425–38.
Jab?o?ska-Trypu? A, Kr?towski R, Kalinowska M, ?widerski G, Cechowska-Pasko M, Lewandowski W. Possible mechanisms of the prevention of doxorubicin toxicity by cichoric acid—antioxidant nutrient. Nutrients 2018;10(1):44.
Tocchetti CG, Cadeddu C, Di Lisi D, Femmino S, Madonna R, Mele D, et al. From molecular mechanisms to clinical management of antineoplastic drug-induced cardiovascular toxicity: a translational overview. Antioxid Redox Signal 2019;30(18):2110–53.
Roti Roti EC, Salih SM. Dexrazoxane ameliorates doxorubicin-induced injury in mouse ovarian cells. Biol Reprod 2012;86(3):96.
Mohajeri M, Sahebkar A. Protective effects of curcumin against doxorubicin-induced toxicity and resistance: A review. Crit Rev Oncol Hematol 2018;122:30–51.
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