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Talebi, A., Hayati Roodbari, N., Reza Sameni, H., & Zarbakhsh, S. (2020). Impact of coadministration of apigenin and bone marrow stromal cells on damaged ovaries due to chemotherapy in rat: An experimental study. International Journal of Reproductive BioMedicine (IJRM), 13(7), 551–560. https://doi.org/10.18502/ijrm.v13i7.7372
https://doi.org/10.18502/ijrm.v13i7.7372
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- Cited by 2 articles
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Athar Talebi
Athar Talebi
Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
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Nasim Hayati Roodbari
Nasim Hayati Roodbari
Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
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Hamid Reza Sameni
Hamid Reza Sameni
Nervous System Stem Cells Research Center, Semnan University of Medical Sciences, Semnan, Iran
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Sam Zarbakhsh
Sam Zarbakhsh
Nervous System Stem Cells Research Center, Semnan University of Medical Sciences, Semnan, Iran
Published Date
- Jul 22, 2020
Impact of coadministration of apigenin and bone marrow stromal cells on damaged ovaries due to chemotherapy in rat: An experimental study
Abstract
Background: Apigenin is a plant-derived flavonoid with antioxidative and antiapoptotic effects. Bone marrow stromal cells (BMSCs) are a type of mesenchymal stem cells (MSCs) that may recover damaged ovaries. It seems that apigenin may promote the differentiation of MSCs.
Objective: The aim of this study was to investigate the effect of coadministration of apigenin and BMSCs on the function, structure, and apoptosis of the damaged ovaries after creating a chemotherapy model with cyclophosphamide in rat.
Materials and Methods: For chemotherapy induction and ovary destruction, cyclophosphamide was injected intraperitoneally to 40 female Wistar rats (weighing 180–200 gr, 10 wk old) for 14 days. Then, the rats were randomly divided into four groups (n = 10/each): control, apigenin, BMSCs and coadministration of apigenin and BMSCs. Injection of apigenin was performed intraperitoneally and BMSC transplantation was performed locally in the ovaries. The level of anti-mullerian hormone serum by ELISA kit, the number of oocytes by superovulation, the number of ovarian follicles in different stages by H&E staining, and the expression of ovarian Bcl-2 and Bax proteins by western blot were assessed after four wk.
Results: The results of serum anti-mullerian hormone level, number of oocytes and follicles, and Bcl-2/Bax expression ratio showed that coadministration of apigenin and BMSCs significantly recovered the ovarian function, structure, and apoptosis compared to the control, BMSC, and apigenin groups (p < 0.001).
Conclusion: The results suggest that the effect of coadministration of apigenin and BMSCs is maybe more effective than the effect of their administrations individually on the recovery of damaged ovaries following the chemotherapy with cyclophosphamide in rats.
Key words: Apigenin, Bone marrow stromal cells, Chemotherapy, Ovary, Regeneration.
References
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[2] Dolmans MM, Demylle D, Martinez-Madrid B, Donnez J. Efficacy of in vitro fertilization after chemotherapy. Fertil Steril 2005; 83: 897–901.
[3] Hamzeh M, Hosseinimehr SJ, Mohammadi HR, Yaghubi Beklar S, Dashti A, Talebpour Amiri F. Atorvastatin attenuates the ovarian damage induced by cyclophosphamide in rat: An experimental study. Int J Reprod Biomed 2018; 16: 323–334.
[4] Liu T, Qin W, Huang Y, Zhao Y, Wang J. Induction of estrogen-sensitive epithelial cells derived from human induced pluripotent stem cells to repair ovarian function in a chemotherapy-induced mouse model of premature ovarian failure. DNA Cell Biol 2013; 32: 685–698.
[5] Nandy SB, Gangwani L, Nahleh Z, Subramani R, Arumugam A, de la Rosa JM, et al. Recurrence and metastasis of breast cancer is influenced by ovarian hormone’s effect on breast cancer stem cells. Future Oncol 2015; 11: 983–995.
[6] Varghese AC, du Plessis SS, Falcone T, Agarwal A. Cryopreservation/transplantation of ovarian tissue and in vitro maturation of follicles and oocytes: challenges for fertility preservation. Reprod Biol Endocrinol 2008; 6: 47–56.
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[8] Dawn B, Bolli R. Adult bone marrow-derived cells: regenerative potential, plasticity, and tissue commitment. Basic Res Cardiol 2005; 100: 494–503.
[9] Tang AQ, Cao XC, Tian L, He L, Liu F. Apigenin inhibits the self-renewal capacity of human ovarian cancer SKOV3- derived sphere-forming cells. Mol Med Rep 2015; 11: 2221– 2226.
[10] Safari M, Parsaie H, Sameni HR, Aldaghi MR, Zarbakhsh S. Anti-oxidative and anti-apoptotic effects of apigenin on number of viable and apoptotic blastomeres, zona pellucida thickness and hatching rate of mouse embryos. Int J Fertil Steril 2018; 12: 257–262.
[11] Sharma H, Kanwal R, Bhaskaran N, Gupta S. Plant flavone apigenin binds to nucleic acid bases and reduces oxidative DNA damage in prostate epithelial cells. PLoS One 2014; 9: e91588.
[12] Zhang X, Zhou C, Zha X, Xu Z, Li L, Liu Y, et al. Apigenin promotes osteogenic differentiation of human mesenchymal stem cells through JNK and p38 MAPK pathways. Mol Cell Biochem 2015; 407: 41–50.
[13] Samet I, Villareal MO, Motojima H, Han J, Sayadi S, Isoda H. Olive leaf components apigenin 7-glucoside and luteolin 7-glucoside direct human hematopoietic stem cell differentiation towards erythroid lineage. Differentiation 2015; 89: 146–155.
[14] Safari M, Jafari B, Zarbakhsh S, Sameni H, Vafaei AA, Mohammadi NK, et al. G-CSF for mobilizing transplanted bone marrow stem cells in rat model of Parkinson’s disease. Iran J Basic Med Sci 2016; 19: 1318–1324.
[15] Haydari S, Safari M, Zarbakhsh S, Bandegi AR, Miladi- Gorji H. Effects of voluntary exercise on the viability, proliferation and BDNF levels of bone marrow stromal cells in rat pups born from morphine-dependent mothers during pregnancy. Neurosci Lett 2016; 634: 132–137.
[16] Takehara Y, Yabuuchi A, Ezoe K, Kuroda T, Yamadera R, Sano C, et al. The restorative effects of adipose-derived mesenchymal stem cells on damaged ovarian function. Lab Invest 2013; 93: 181–193.
[17] Song D, Zhong Y, Qian C, Zou Q, Ou J, Shi Y, et al. Human umbilical cord mesenchymal stem cells therapy in cyclophosphamide-induced premature ovarian failure rat model. Biomed Res Int 2016; 2016: 2517514.
[18] Anusha C, Sumathi T, Joseph LD. Protective role of apigenin on rotenone-induced rat model of Parkinson’s disease: Suppression of neuroinflammation and oxidative stress-mediated apoptosis. Chem Biol Interact 2017; 269: 67–79.
[19] Ling L, Feng X, Wei T, Wang Y, Wang Y, Wang Z, et al. Human amnion-derived mesenchymal stem cell (hADMSC) transplantation improves ovarian function in rats with premature ovarian insufficiency (POI) at least partly through a paracrine mechanism. Stem Cell Res Ther 2019; 10: 46–63.
[20] Dayangan Sayan C, Tulmac OB, Karaca G, Ozkan ZS, Yalcin S, Devrim T, et al. Could erythropoietin reduce the ovarian damage of cisplatin in female rats? Gynecol Endocrinol 2018; 34: 309–313.
[21] Sameni HR, Seiri M, Safari M, Tabrizi Amjad MH, Khanmohammadi N, Zarbakhsh S. Bone marrow stromal cells with the granulocyte colony-stimulating factor in the management of chemotherapy-induced ovarian failure in a rat model. Iran J Med Sci 2019; 44: 135–145.
[22] Mesbah F, Bordbar H, Talaei Khozani T, Dehghani F, Mirkhani H. The non-preventive effects of human menopausal gonadotropins on ovarian tissues in Nandrolone decanoate-treated female rats: A histochemical and ultra-structural study. Int J Reprod Biomed 2018; 16: 159–174.
[23] Kalhori Z, Soleimani Mehranjani M, Azadbakht M, Shariaatzadeh MA. Ovary stereological features and serum biochemical factors following induction of polycystic ovary syndrome with testosterone enanthate in mice: An experimental study. Int J Reprod Biomed 2018; 16: 267–274.
[24] Bas D, Abramovich D, Hernandez F, Tesone M. Altered expression of Bcl-2 and Bax in follicles within dehydroepiandrosterone-induced polycystic ovaries in rats. Cell Biol Int 2011; 35: 423–429.
[25] Peigné M, Decanter C. Serum AMH level as a marker of acute and long-term effects of chemotherapy on the ovarian follicular content: a systematic review. Reprod Biol Endocrinol 2014; 12: 26–35.
[26] Zarbakhsh S, Safari R, Sameni HR, Yousefi B, Safari M, Khanmohammadi N, et al. Effects of co-administration of bone marrow stromal cells and L-carnitine on the recovery of damaged ovaries by performing chemotherapy model in rat. Int J Fertil Steril 2019; 13: 196–202.
[27] Guo JQ, Gao X, Lin ZJ, Wu WZ, Huang LH, Dong HY, et al. BMSCs reduce rat granulosa cell apoptosis induced by cisplatin and perimenopause. BMC Cell Biol 2013; 14: 18– 26.
[28] Liu S, Zhou J, Zhang X, Liu Y, Chen J, Hu B, et al. Strategies to optimize adult stem cell therapy for tissue regeneration. Int J Mol Sci 2016; 17: 982–997.
[29] Soyman Z, Kelekçi S, Sal V, Şevket O, Bayındır N, Uzun H. Effects of apigenin on experimental ischemia/reperfusion injury in the rat ovary. Balkan Med J 2017; 34: 444–449.
[30] Zhang F, Li F, Chen G. Neuroprotective effect of apigenin in rats after contusive spinal cord injury. Neurol Sci 2014; 35: 583–588.
[31] Liu L, Peng Z, Xu Z, Wei X. Effect of luteolin and apigenin on the expression of Oct-4, Sox2, and c-Myc in dental pulp cells with in vitro culture. Biomed Res Int 2015; 2015: 534952.
[32] Jung UJ, Cho YY, Choi MS. Apigenin ameliorates dyslipidemia, hepatic steatosis and insulin resistance by modulating metabolic and transcriptional profiles in the liver of high-fat diet-induced obese mice. Nutrients 2016; 8: 305–320.
[33] Wang S, He G, Chen M, Zuo T, Xu W, Liu X. The role of antioxidant enzymes in the ovaries. Oxid Med Cell Longev 2017; 2017: 4371714.
[34] Mao AS, Shin JW, Mooney DJ. Effects of substrate stiffness and cell-cell contact on mesenchymal stem cell differentiation. Biomaterials 2016; 98: 184–191.
[35] Zhang HT, Zha ZG, Cao JH, Liang ZJ, Wu H, He MT, et al. Apigenin accelerates lipopolysaccharide-induced apoptosis in mesenchymal stem cells through suppressing vitamin D receptor expression. Chin Med J 2011; 124: 3537–3545.
[2] Dolmans MM, Demylle D, Martinez-Madrid B, Donnez J. Efficacy of in vitro fertilization after chemotherapy. Fertil Steril 2005; 83: 897–901.
[3] Hamzeh M, Hosseinimehr SJ, Mohammadi HR, Yaghubi Beklar S, Dashti A, Talebpour Amiri F. Atorvastatin attenuates the ovarian damage induced by cyclophosphamide in rat: An experimental study. Int J Reprod Biomed 2018; 16: 323–334.
[4] Liu T, Qin W, Huang Y, Zhao Y, Wang J. Induction of estrogen-sensitive epithelial cells derived from human induced pluripotent stem cells to repair ovarian function in a chemotherapy-induced mouse model of premature ovarian failure. DNA Cell Biol 2013; 32: 685–698.
[5] Nandy SB, Gangwani L, Nahleh Z, Subramani R, Arumugam A, de la Rosa JM, et al. Recurrence and metastasis of breast cancer is influenced by ovarian hormone’s effect on breast cancer stem cells. Future Oncol 2015; 11: 983–995.
[6] Varghese AC, du Plessis SS, Falcone T, Agarwal A. Cryopreservation/transplantation of ovarian tissue and in vitro maturation of follicles and oocytes: challenges for fertility preservation. Reprod Biol Endocrinol 2008; 6: 47–56.
[7] Khanmohammadi N, Sameni HR, Mohammadi M, Pakdel A, Mirmohammadkhani M, Parsaie H, et al. Effect of transplantation of bone marrow stromal cell-conditioned medium on ovarian function, morphology and cell death in cyclophosphamide-treated rats. Cell J 2018; 20: 10–18.
[8] Dawn B, Bolli R. Adult bone marrow-derived cells: regenerative potential, plasticity, and tissue commitment. Basic Res Cardiol 2005; 100: 494–503.
[9] Tang AQ, Cao XC, Tian L, He L, Liu F. Apigenin inhibits the self-renewal capacity of human ovarian cancer SKOV3- derived sphere-forming cells. Mol Med Rep 2015; 11: 2221– 2226.
[10] Safari M, Parsaie H, Sameni HR, Aldaghi MR, Zarbakhsh S. Anti-oxidative and anti-apoptotic effects of apigenin on number of viable and apoptotic blastomeres, zona pellucida thickness and hatching rate of mouse embryos. Int J Fertil Steril 2018; 12: 257–262.
[11] Sharma H, Kanwal R, Bhaskaran N, Gupta S. Plant flavone apigenin binds to nucleic acid bases and reduces oxidative DNA damage in prostate epithelial cells. PLoS One 2014; 9: e91588.
[12] Zhang X, Zhou C, Zha X, Xu Z, Li L, Liu Y, et al. Apigenin promotes osteogenic differentiation of human mesenchymal stem cells through JNK and p38 MAPK pathways. Mol Cell Biochem 2015; 407: 41–50.
[13] Samet I, Villareal MO, Motojima H, Han J, Sayadi S, Isoda H. Olive leaf components apigenin 7-glucoside and luteolin 7-glucoside direct human hematopoietic stem cell differentiation towards erythroid lineage. Differentiation 2015; 89: 146–155.
[14] Safari M, Jafari B, Zarbakhsh S, Sameni H, Vafaei AA, Mohammadi NK, et al. G-CSF for mobilizing transplanted bone marrow stem cells in rat model of Parkinson’s disease. Iran J Basic Med Sci 2016; 19: 1318–1324.
[15] Haydari S, Safari M, Zarbakhsh S, Bandegi AR, Miladi- Gorji H. Effects of voluntary exercise on the viability, proliferation and BDNF levels of bone marrow stromal cells in rat pups born from morphine-dependent mothers during pregnancy. Neurosci Lett 2016; 634: 132–137.
[16] Takehara Y, Yabuuchi A, Ezoe K, Kuroda T, Yamadera R, Sano C, et al. The restorative effects of adipose-derived mesenchymal stem cells on damaged ovarian function. Lab Invest 2013; 93: 181–193.
[17] Song D, Zhong Y, Qian C, Zou Q, Ou J, Shi Y, et al. Human umbilical cord mesenchymal stem cells therapy in cyclophosphamide-induced premature ovarian failure rat model. Biomed Res Int 2016; 2016: 2517514.
[18] Anusha C, Sumathi T, Joseph LD. Protective role of apigenin on rotenone-induced rat model of Parkinson’s disease: Suppression of neuroinflammation and oxidative stress-mediated apoptosis. Chem Biol Interact 2017; 269: 67–79.
[19] Ling L, Feng X, Wei T, Wang Y, Wang Y, Wang Z, et al. Human amnion-derived mesenchymal stem cell (hADMSC) transplantation improves ovarian function in rats with premature ovarian insufficiency (POI) at least partly through a paracrine mechanism. Stem Cell Res Ther 2019; 10: 46–63.
[20] Dayangan Sayan C, Tulmac OB, Karaca G, Ozkan ZS, Yalcin S, Devrim T, et al. Could erythropoietin reduce the ovarian damage of cisplatin in female rats? Gynecol Endocrinol 2018; 34: 309–313.
[21] Sameni HR, Seiri M, Safari M, Tabrizi Amjad MH, Khanmohammadi N, Zarbakhsh S. Bone marrow stromal cells with the granulocyte colony-stimulating factor in the management of chemotherapy-induced ovarian failure in a rat model. Iran J Med Sci 2019; 44: 135–145.
[22] Mesbah F, Bordbar H, Talaei Khozani T, Dehghani F, Mirkhani H. The non-preventive effects of human menopausal gonadotropins on ovarian tissues in Nandrolone decanoate-treated female rats: A histochemical and ultra-structural study. Int J Reprod Biomed 2018; 16: 159–174.
[23] Kalhori Z, Soleimani Mehranjani M, Azadbakht M, Shariaatzadeh MA. Ovary stereological features and serum biochemical factors following induction of polycystic ovary syndrome with testosterone enanthate in mice: An experimental study. Int J Reprod Biomed 2018; 16: 267–274.
[24] Bas D, Abramovich D, Hernandez F, Tesone M. Altered expression of Bcl-2 and Bax in follicles within dehydroepiandrosterone-induced polycystic ovaries in rats. Cell Biol Int 2011; 35: 423–429.
[25] Peigné M, Decanter C. Serum AMH level as a marker of acute and long-term effects of chemotherapy on the ovarian follicular content: a systematic review. Reprod Biol Endocrinol 2014; 12: 26–35.
[26] Zarbakhsh S, Safari R, Sameni HR, Yousefi B, Safari M, Khanmohammadi N, et al. Effects of co-administration of bone marrow stromal cells and L-carnitine on the recovery of damaged ovaries by performing chemotherapy model in rat. Int J Fertil Steril 2019; 13: 196–202.
[27] Guo JQ, Gao X, Lin ZJ, Wu WZ, Huang LH, Dong HY, et al. BMSCs reduce rat granulosa cell apoptosis induced by cisplatin and perimenopause. BMC Cell Biol 2013; 14: 18– 26.
[28] Liu S, Zhou J, Zhang X, Liu Y, Chen J, Hu B, et al. Strategies to optimize adult stem cell therapy for tissue regeneration. Int J Mol Sci 2016; 17: 982–997.
[29] Soyman Z, Kelekçi S, Sal V, Şevket O, Bayındır N, Uzun H. Effects of apigenin on experimental ischemia/reperfusion injury in the rat ovary. Balkan Med J 2017; 34: 444–449.
[30] Zhang F, Li F, Chen G. Neuroprotective effect of apigenin in rats after contusive spinal cord injury. Neurol Sci 2014; 35: 583–588.
[31] Liu L, Peng Z, Xu Z, Wei X. Effect of luteolin and apigenin on the expression of Oct-4, Sox2, and c-Myc in dental pulp cells with in vitro culture. Biomed Res Int 2015; 2015: 534952.
[32] Jung UJ, Cho YY, Choi MS. Apigenin ameliorates dyslipidemia, hepatic steatosis and insulin resistance by modulating metabolic and transcriptional profiles in the liver of high-fat diet-induced obese mice. Nutrients 2016; 8: 305–320.
[33] Wang S, He G, Chen M, Zuo T, Xu W, Liu X. The role of antioxidant enzymes in the ovaries. Oxid Med Cell Longev 2017; 2017: 4371714.
[34] Mao AS, Shin JW, Mooney DJ. Effects of substrate stiffness and cell-cell contact on mesenchymal stem cell differentiation. Biomaterials 2016; 98: 184–191.
[35] Zhang HT, Zha ZG, Cao JH, Liang ZJ, Wu H, He MT, et al. Apigenin accelerates lipopolysaccharide-induced apoptosis in mesenchymal stem cells through suppressing vitamin D receptor expression. Chin Med J 2011; 124: 3537–3545.