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OBSTETRICS AND GYNAECOLOGY / EXPERIMENTAL RESEARCH
Resveratrol (3,4ʹ,5-trihydroxy-trans-stilbene) or caffeic acid phenethyl ester supplementation prevents premature ovarian insufficiency due to chemotherapy
1
Department of Obstetrics and Gynecology, Altinbas University, Istanbul, Turkey
Submission date: 2020-05-07
Final revision date: 2020-08-02
Acceptance date: 2020-08-13
Online publication date: 2020-11-15
Publication date: 2026-06-30
Corresponding author
Arch Med Sci 2026;22(3):1875-1881
KEYWORDS
TOPICS
ABSTRACT
Introduction:
This study was planned to investigate the protective effect of resveratrol (RSV), caffeic acid phenethyl ester (CAPE), and coenzyme Q10 (CoQ10) on chemotherapy-induced premature ovarian insufficiency (POI).
Material and methods:
Twenty-eight female rats were divided into four groups with 7 rats in each group. The groups consisted of a vehicle-treated control group (group 1), rats treated with chemotherapy followed by intraperitoneal RSV injection (group 2) or rats treated with chemotherapy followed by CoQ10 (group 3), or rats treated with chemotherapy followed by intraperitoneal CAPE injection (group 4). Cisplatin was administered intraperitoneally once daily at doses of 2.0 mg/kg for 10 days. Rats in groups 2, 3, and 4 were given RSV (100 mg/kg, i.p.), CoQ10 (20 mg/kg, oral), and CAPE (10 mg/kg, i.p.) respectively. Five animals in the sham group underwent laparotomy for ovarian weight measurements on the first day of cisplatin injection. Animals in the treatment and control groups were sacrificed 2 weeks later, and their ovaries were excised for histopathological analysis. Serum levels of anti-Mullerian hormone (AMH) were also analyzed.
Results:
Rats in groups 2 and 4 showed vaginal smears under estrogenic effect. At the end of the second week, the total body weight and ovarian weight of the animals in group 1 increased. Significantly higher mean follicle count was detected in groups 2 and group 4 compared to group 3. The ovaries of the rats in the control group showed follicles in all stages of development. While the ovaries of the rats in the RSV or CAPE showed significantly decreased numbers of primordial follicles they showed increased numbers of early growing follicles.
Conclusions:
Both RSV and CAPE administration might improve follicle survival and AMH production in rats with chemotherapy-induced POI but further research is necessary.
This study was planned to investigate the protective effect of resveratrol (RSV), caffeic acid phenethyl ester (CAPE), and coenzyme Q10 (CoQ10) on chemotherapy-induced premature ovarian insufficiency (POI).
Material and methods:
Twenty-eight female rats were divided into four groups with 7 rats in each group. The groups consisted of a vehicle-treated control group (group 1), rats treated with chemotherapy followed by intraperitoneal RSV injection (group 2) or rats treated with chemotherapy followed by CoQ10 (group 3), or rats treated with chemotherapy followed by intraperitoneal CAPE injection (group 4). Cisplatin was administered intraperitoneally once daily at doses of 2.0 mg/kg for 10 days. Rats in groups 2, 3, and 4 were given RSV (100 mg/kg, i.p.), CoQ10 (20 mg/kg, oral), and CAPE (10 mg/kg, i.p.) respectively. Five animals in the sham group underwent laparotomy for ovarian weight measurements on the first day of cisplatin injection. Animals in the treatment and control groups were sacrificed 2 weeks later, and their ovaries were excised for histopathological analysis. Serum levels of anti-Mullerian hormone (AMH) were also analyzed.
Results:
Rats in groups 2 and 4 showed vaginal smears under estrogenic effect. At the end of the second week, the total body weight and ovarian weight of the animals in group 1 increased. Significantly higher mean follicle count was detected in groups 2 and group 4 compared to group 3. The ovaries of the rats in the control group showed follicles in all stages of development. While the ovaries of the rats in the RSV or CAPE showed significantly decreased numbers of primordial follicles they showed increased numbers of early growing follicles.
Conclusions:
Both RSV and CAPE administration might improve follicle survival and AMH production in rats with chemotherapy-induced POI but further research is necessary.
REFERENCES (45)
1.
Banu SK, Stanley JA, Sivakumar KK, Arosh JA, Burghardt RC. Resveratrol protects the ovary against chromium-toxicity by enhancing endogenous antioxidant enzymes and inhibiting metabolic clearance of estradiol. Toxicol Appl Pharmacol 2016; 303: 65-78.
2.
Jiang Y, Zhang Z, Cha L, et al. Resveratrol plays a protective role against premature ovarian failure and prompts female germline stem cell survival. Int J Mol Sci 2019; 20: 3605.
3.
Said RS, El-Demerdash E, Nada AS, Kamal MM. Resveratrol inhibits inflammatory signaling implicated in ionizing radiation-induced premature ovarian failure through antagonistic crosstalk between silencing information regulator 1 (SIRT1) and poly(ADP-ribose) polymerase 1 (PARP-1). Biochem Pharmacol 2016; 103: 140-50.
4.
Oktay K, Harvey BE, Partridge AH, et al. Fertility preservation in patients with cancer: ASCO clinical practice guideline update. J Clin Oncol 2018; 36: 1994-2001.
5.
Spears N, Lopes F, Stefansdottir A, et al. Ovarian damage from chemotherapy and current approaches to its protection. Hum Reprod Update 2019; 25: 673-93.
6.
Sinha D, Biswas J, Sung B, Agarwal BB, Bishayee A. Chemopreventive and chemotherapeutic potential of curcumin in breast cancer. Current Drug Targets 2012; 13: 1799-819.
7.
Desai AG, Qazi GN, Ganju RK, et al. Medicinal plants and cancer chemoprevention. Curr Drug Metab 2008; 9: 581-91.
8.
Shukla Y, Singh R. Resveratrol and cellular mechanisms of cancer prevention. Ann N Y Acad Sci 2011; 1215: 1-8.
9.
Kulkarni SS, Cantó C. The molecular targets of resveratrol. Biochim Biophys Acta 2015; 1852: 1114-23.
10.
Bitterman JL, Chung JH. Metabolic effects of resveratrol: addressing the controversies. Cell Mol Life Sci 2015; 72: 1473-88.
11.
Zordoky BNM, Robertson IM, Dyck JRB. Preclinical and clinical evidence for the role of resveratrol in the treatment of cardiovascular diseases. Biochim Biophys Acta 2015; 1852: 1155-77.
13.
Hascalik S, Celik O, Turkoz Y, et al. Resveratrol, a red wine constituent polyphenol, protects from ischemia-reperfusion damage of the ovaries. Gynecol Obstet Invest 2004; 57: 218-23.
14.
Aires V, Limagne E, Cotte AK, Latruffe N, Ghiringhelli F, Delmas D. Resveratrol metabolites inhibit human metastatic colon cancer cells progression and synergize with chemotherapeutic drugs to induce cell death. Mol Nutr Food Res 2013; 57: 1170-81.
15.
Celik O, Turkoz Y, Hascalik S, et al. The protective effect of caffeic acid phenethyl ester on ischemia-reperfusion injury in rat ovary. Eur J Obstet Gynecol Reprod Biol 2004; 117: 183-8.
16.
Grunberger D, Banerjee R, Eisinger K, et al. Preferential cytotoxicity on tumor cells by caffeic acid phenethyl ester isolated from propolis. Experientia 1988; 44: 230-2.
17.
Mansfield KD, Guzy RD, Pan Y, et al. Mitochondrial dysfunction resulting from loss of cytochrome c impairs cellular oxygen sensing and hypoxic HIF-alpha activation. Cell Metab 2005; 1: 393-9.
18.
Bentinger M, Tekle M, Brismar K, Chojnacki T, Swiezewska E, Dallner G. Stimulation of coenzyme Q synthesis. Biofactors 2008; 32: 99-111.
19.
Ozcan P, Fıçıcıoğlu C, Kizilkale O, et al. Can coenzyme Q10 supplementation protect the ovarian reserve against oxidative damage? J Assist Reprod Genet 2016; 33: 1223-30.
20.
Jang H, Lee OH, Lee Y, et al. Melatonin prevents cisplatin-induced primordial follicle loss via suppression of PTEN/AKT/FOXO3a pathway activation in the mouse ovary. J Pineal Res 2016; 60: 336-47.
21.
Dash S, Xiao C, Morgantini C, Lewis GF. New insights into the regulation of chylomicron production. Annu Rev Nutr 2015; 35: 265-94.
22.
Planas JM, Alfaras I, Colom H, Juan ME. The bioavailability and distribution of trans-resveratrol are constrained by ABC transporters. Arch Biochem Biophys 2012; 527: 67-73.
23.
Celik O, Celik E, Turkcuoglu I, et al. Surgical removal of endometrioma decreases the NF-kB1 (p50/105) and NF-kB p65 (Rel A) expression in the eutopic endometrium during the implantation window. Reprod Sci 2013; 20: 762-70.
24.
Myers M, Britt KL, Wreford NG, Ebling FJ, Kerr JB. Methods for quantifying follicular numbers within the mouse ovary. Reproduction 2004; 127: 569-80.
25.
Soleimani R, Heytens E, Darzynkiewicz Z, Oktay K. Mechanisms of chemotherapyinduced human ovarian aging: double strand DNA breaks and microvascular compromise. Aging (Albany NY) 2011; 3: 782-93.
26.
Oktay K, Turan V, Titus S, Stobezki R, Liu L. BRCA mutations, DNA repair deficiency, and ovarian aging. Biol Reprod 2015; 93: 67.
27.
Soleimani R, Heytens E, Oktay K. Enhancement of neoangiogenesis and follicle survival by sphingosine-1-phosphate in human ovarian tissue xenotransplants. PLoS One 2011; 6: e19475.
28.
Wang D, Xiang DB, He YJ, et al. Effect of caffeic acid phenethyl ester on proliferation and apoptosis of colorectal cancer cells in vitro. World J Gastroenterol 2005; 11: 4008-12.
29.
He YJ, Liu BH, Xiang DB, Qiao ZY, Fu T, He YH. Inhibitory effect of caffeic acid phenethyl ester on the growth of SW480 colorectal tumor cells involves beta-catenin associated signaling pathway down-regulation. World J Gastroenterol 2006; 12: 4981-5.
30.
Lee KW, Chun KS, Lee JS, Kang KS, Surh YJ, Lee HJ. Inhibition of cyclooxygenase-2 expression and restoration of gap junction intercellular communication in H-ras-transformed rat liver epithelial cells by caffeic acid phenethyl ester. Ann N Y Acad Sci 2004; 1030: 501-7.
31.
Athar M, Back JH, Kopelovich L, Bickers DR, Kim AL. Multiple molecular targets of resveratrol: anti-carcinogenic mechanisms. Arch Biochem Biophys 2009; 486: 95-102.
32.
Hussain AR, Al-Rasheed M, Manogaran PS, et al. Curcumin induces apoptosis via inhibition of PI3’-kinase/AKT pathway in acute T cell leukemias. Apoptosis 2006; 11: 245-54.
33.
Juan ME, Wenzel U, Daniel H, Planas JM. Resveratrol induces apoptosis through ROS-dependent mitochondria pathway in HT-29 human colorectal carcinoma cells. J Agric Food Chem 2008; 56: 4813-8.
34.
Cicero AFG, Ruscica M, Banach M. Resveratrol and cognitive decline: a clinician perspective. Arch Med Sci 2019; 15: 936-43.
35.
Sergi C, Chiu B, Feulefack J, Shen F, Chiu B. Usefulness of resveratrol supplementation in decreasing cardiometabolic risk factors comparing subjects with metabolic syndrome and healthy subjects with or without obesity: meta-analysis using multinational, randomised, controlled trials. Arch Med Sci Atheroscler Dis 2020; 5: e98-111.
36.
Aberg F, Appelkvist El, Dallner G, Ernster L. Distribution and redox state of ubiquinones in rat and human tissues. Arch Biochem Biophys 1992; 295: 230-4.
37.
Garrido-Maraver J, Cordero MD, Oropesa-Avila M, et al. Clinical applications of coenzyme Q10. Front Biosci 2014; 19: 619-33.
38.
Kucinska M, Piotrowska H, Luczak MW, et al. Effects of hydroxylated Resveratrol analogs on oxidative stress and cancer cells death in human acute T cell leukemia cell line: prooxidative potential of hydroxylated Resveratrol analogs. Chem Biol Interact 2014; 209: 96-110.
39.
Hussain AR, Uddin S, Bu R, et al. Resveratrol suppresses constitutive activation of AKT via generation of ROS and induces apoptosis in diffuse large B cell lymphoma cell lines. PLoS One 2011; 6: e24703.
40.
Detampel P, Beck M, Krähenbühl S, Huwyler J. Drug interaction potential of resveratrol. Drug Metab Rev 2012; 44: 253-65.
41.
Shimizu T, Nakazato T, Xian MJ, Sagawa M, Ikeda Y, Kizaki M. Resveratrol induces apoptosis of human malignant B cells by activation of caspase-3 and p38 MAP kinase pathways. Biochem Pharmacol 2006; 71: 742-50.
42.
Jancova P, Anzenbacher P, Anzenbacherova E. Phase II drug metabolizing enzymes. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2010; 154: 103-16.
43.
Upadhyay G, Singh AK, Kumar A, Prakash O, Singh MP. Resveratrol modulates pyrogallol-induced changes in hepatic toxicity markers, xenobiotic metabolizing enzymes and oxidative stress. Eur J Pharmacol 2008; 596: 146-52.
44.
McIlwain CC, Townsend DM, Tew KD. Glutathione S-transferase polymorphisms: cancer incidence and therapy. Oncogene 2006; 25: 1639-48.
45.
Ersahin AA, Ersahin S, Gungor ND. Surgical removal of hydrosalpinx improves endometrium receptivity by decreasing nuclear factor-kappa B expression. Reprod Sci 2020; 27: 787-92.
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