Skip to main content
SpringerLink
Log in

Plant isoflavones can prevent adverse effects of benzene on porcine ovarian activity: an in vitro study

  • Research Article
  • Published:
Environmental Science and Pollution Research Aims and scope Submit manuscript

Abstract

We evaluated the influence of the oil-related environmental contaminant benzene (0, 10, 100, or 1000 ng/mL) alone and in combination with apigenin, daidzein, or rutin (10 μg/mL each) on viability; proliferation (accumulation of proliferating cell nuclear antigen); apoptosis (accumulation of Bax); and release of progesterone (P), testosterone (T), and estradiol (E) in cultured porcine ovarian granulosa cells. Cell viability; proliferation; apoptosis; and release of P, T, and E have been analyzed by the trypan blue test, quantitative immunocytochemistry, and ELISA, respectively. Benzene did not affect apoptosis, but reduced ovarian cell viability and P and E release, and promoted proliferation and T output. Apigenin did not affect cell viability, but stimulated proliferation and T and E release, and inhibited apoptosis and P secretion. It prevented and reversed the action of benzene on proliferation and P and T release, and induced the inhibitory action of benzene on apoptosis. Daidzein promoted cell viability, proliferation, P release, but not apoptosis and T or E release. Daidzein induced the stimulatory effect of benzene on T, without modifying other effects. Rutin administered alone reduced cell viability and apoptosis, and promoted cell proliferation. Furthermore, rutin prevented and reversed the effect of benzene on proliferation and P and E release. These observations suggest the direct action of benzene and plant polyphenols on basic ovarian cell functions, and the ability of apigenin and rutin, but not of daidzein, to prevent benzene effects on the ovary.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Alviggi C, Guadagni R, Conforti A, Coppola G, Picarelli S, De Rosa P, Vallone R, Strina I, Pagano T, Mollo A, Acampora A, De Placido G (2014) Association between intrafollicular concentration of benzene and outcome of controlled ovarian stimulation in IVF/ICSI cycles: a pilot study. J Ovarian Res. 18(7):67. https://doi.org/10.1186/1757-2215-7-67

    Article  CAS  Google Scholar 

  • Cederroth CR, Zimmermann C, Nef S (2012) Soy, phytoestrogens and their impact on reproductive health. Mol Cell Endocrinol 355:192–200

    Article  CAS  Google Scholar 

  • Chan KKL, Siu MKY, Jiang YX, Wang JJ, Leung THY, Ngan HYS (2018) Estrogen receptor modulators genistein, daidzein and ERB-041 inhibit cell migration, invasion, proliferation and sphere formation via modulation of FAK and PI3K/AKT signaling in ovarian cancer. Cancer Cell Int 18:65. https://doi.org/10.1186/s12935-018-0559-2

    Article  CAS  Google Scholar 

  • Choi EJ, Kim GH (2014) The antioxidant activity of daidzein metabolites, O-desmethylangolensin and equol, in HepG2 cells. Mol Med Rep 9:328–332

    Article  CAS  Google Scholar 

  • Darabi P, Khazali H, Mehrabani Natanzi M (2019) Therapeutic potentials of the natural plant flavonoid apigenin in polycystic ovary syndrome in rat model: via modulation of pro-inflammatory cytokines and antioxidant activity. Gynecol Endocrinol 30:1–6. https://doi.org/10.1080/09513590.2019.1706084

    Article  CAS  Google Scholar 

  • Dubeyl RK, Rosselli M, Imthurn B, Keller PJ, Jackson EK (2000) Vascular effects of environmental oestrogens: implications for reproductive and vascular health. Hum Reprod Update. 6:351–363

    Article  CAS  Google Scholar 

  • Dull AM, Moga MA, Dimienescu OG, Sechel G, Burtea V, Anastasiu CV (2019) Therapeutic approaches of resveratrol on endometriosis via anti-inflammatory and anti-angiogenic pathways. Molecules 24. https://doi.org/10.3390/molecules24040667

  • Földešiová M, Baláži A, Chrastinová Ľ, Pivko J, Kotwica J, Harrath AH, Chrenek P, Sirotkin AV (2017) Yucca schidigera can promote rabbit growth, fecundity, affect the release of hormones in vivo and in vitro, induce pathological changes in liver, and reduce ovarian resistance to benzene. Anim Reprod Sci 183:66–76. https://doi.org/10.1016/j.anireprosci.2017.06.001

    Article  CAS  Google Scholar 

  • Ganeshpurkar A, Saluja AK (2017) The pharmacological potential of rutin. Saudi Pharm J 25(2):149–164. https://doi.org/10.1016/j.jsps.2016.04.025

    Article  Google Scholar 

  • Hu T, Yuan X, Ye R, Zhou H, Lin J, Zhang C, Zhang H, Wei G, Dong M, Huang Y, Lim W, Liu Q, Lee HJ, Jin W (2017) Brown adipose tissue activation by rutin ameliorates polycystic ovary syndrome in rat. J Nutr Biochem 47:21–28. https://doi.org/10.1016/j.jnutbio.2017.04.012

    Article  CAS  Google Scholar 

  • IARC Working Group on the Evaluation of Carcinogenic Risks to Humans (2018) Benzene. International Agency for Research on Cancer, Lyon (FR)

    Google Scholar 

  • Medigović IM, Živanović JB, Ajdžanović VZ, Nikolić-Kokić AL, Stanković SD, Trifunović SL, Milošević VLJ, Nestorović NM (2015) Effects of soy phytoestrogens on pituitary-ovarian function in middle-aged female rats. Endocrine 50(3):764–776. https://doi.org/10.1007/s12020-015-0691-x

    Article  CAS  Google Scholar 

  • Mehfooz A, Wei Q, Zheng K, Fadlalla MB, Maltasic G, Shi F (2018) Protective roles of rutin against restraint stress on spermatogenesis in testes of adult mice. Tissue Cell 50:133–143. https://doi.org/10.1016/j.tice.2018.01.003

    Article  CAS  Google Scholar 

  • Nynca A, Słonina D, Jablońska O, Kamińska B, Ciereszko RE (2013) Daidzein affects steroidogenesis and oestrogen receptor expression in medium ovarian follicles of pigs. Acta Vet Hung 61(1):85–98. https://doi.org/10.1556/AVet.2012.060

    Article  CAS  Google Scholar 

  • Peña-Blanco A, García-Sáez AJ (2018) Bax, Bak and beyond - mitochondrial performance in apoptosis. FEBS J 285:416–431. https://doi.org/10.1111/febs.14186

    Article  CAS  Google Scholar 

  • Protano C, Scalise T, Orsi GB, Vitali M (2012) A systematic review of benzene exposure during pregnancy and adverse outcomes on intrauterine development and birth: still far from scientific evidence. Ann Ig 24:451–463

    CAS  Google Scholar 

  • Salehi B, Venditti A, Sharifi-Rad M, Kręgiel D, Sharifi-Rad J, Durazzo A, Lucarini M, Santini A, Souto EB, Novellino E, Antolak H, Azzini E, Setzer WN, Martins N (2019) The therapeutic potential of apigenin. Int J Mol Sci, 20(6):E1305. https://doi.org/10.3390/ijms20061305

  • Shiomi Y, Nishitani H (2017) Control of genome integrity by RFC complexes; conductors of PCNA loading onto and unloading from chromatin during DNA replication. Genes 8:E52. https://doi.org/10.3390/genes8020052

    Article  CAS  Google Scholar 

  • Sirotkin AV (2014) Regulators of ovarian functions, second edn. Nova Science Publishers, Inc New York

  • Sirotkin AV, Harrath AH (2014) Phytoestrogens and their effects. Eur J Pharmacol 741:230–236. https://doi.org/10.1016/j.ejphar.2014.07.057

    Article  CAS  Google Scholar 

  • Sirotkin AV, Harrath AH (2017) Influence of oil-related environmental pollutants on female reproduction. Reprod Toxicol 71:142–145

    Article  CAS  Google Scholar 

  • Sirotkin AV, Alexa R, Kádasi A, Štochmaľová A, Morovič M, Laurinčik J, Harrath AH, Grossmann R (2017a) The isoflavone daidzein directly affects porcine ovarian cell functions and modifies the effect of follicle-stimulating hormone. J Anim Physiol Anim Nutr (Berl) 101(1):127–135. https://doi.org/10.1111/jpn.12520

    Article  CAS  Google Scholar 

  • Sirotkin AV, Fabian D, Babel’ová Kubandová J, Vlčková R, Alwasel S, Harrath AH (2017b) Metabolic state can define the ovarian response to environmental contaminants and medicinal plants. Appl Physiol Nutr Metab 42(12):1264–1269. https://doi.org/10.1139/apnm-2017-0262

    Article  CAS  Google Scholar 

  • Sirotkin AV, Kadasi A, Baláži A, Kotwica J, Alrezaki A, Harrath AH (2019) Mechanisms of the direct effects of oil-related contaminants on ovarian cells. Environ Sci Pollut Res Int. https://doi.org/10.1007/s11356-019-07295-0

  • Soyman Z, Kelekçi S, Sal V, Şevket O, Bayındır N, Uzun H (2017) Effects of apigenin on experimental ischemia/reperfusion injury in the rat ovary. Balkan Med J 34(5):444–449. https://doi.org/10.4274/balkanmedj.2016.1386

    Article  CAS  Google Scholar 

  • Talsness C, Grote K, Kuriyama S, Presibella K, Sterner-Kock A, Poça K, Chahoud I (2015) Prenatal exposure to the phytoestrogen daidzein resulted in persistent changes in ovarian surface epithelial cell height, folliculogenesis, and estrus phase length in adult Sprague-Dawley rat offspring. J Toxicol Environ Health A 78(10):635–644. https://doi.org/10.1080/15287394.2015.1006711

    Article  CAS  Google Scholar 

  • Tarko A, Štochmal’ová A, Jedličková K, Hrabovszká S, Vachanová A, Harrath AH, Alwasel S, Alrezaki A, Kotwica J, Baláži A, Sirotkin AV (2019) Effects of benzene, quercetin, and their combination on porcine ovarian cell proliferation, apoptosis, and hormone release. Arch Anim Breed 62(1):345–351. https://doi.org/10.5194/aab-62-345-2019

    Article  Google Scholar 

  • Tavsan Z, Kayali HA (2019) Flavonoids showed anticancer effects on the ovarian cancer cells: Involvement of reactive oxygen species, apoptosis, cell cycle and invasion. Biomed Pharmacother 116:109004. https://doi.org/10.1016/j.biopha.2019.109004

    Article  CAS  Google Scholar 

  • Tiemann U, Schneider F, Vanselow J, Tomek W (2007) In vitro exposure of porcine granulosa cells to the phytoestrogens genistein and daidzein: effects on the biosynthesis of reproductive steroid hormones. Reprod Toxicol 24:317–325

    Article  CAS  Google Scholar 

  • Van Duursen MBM (2017) Modulation of estrogen synthesis and metabolism by phytoestrogens in vitro and the implications for women’s health. Toxicol Res (Camb). 6:772–794. https://doi.org/10.1039/c7tx00184c

    Article  CAS  Google Scholar 

  • Wang W, Sun Y, Liu J, Li Y, Li H, Xiao S, Weng S, Zhang W (2014) Soy isoflavones administered to rats from weaning until sexual maturity affect ovarian follicle development by inducing apoptosis. Food Chem Toxicol 72:51–60. https://doi.org/10.1016/j.fct.2014.07.010

    Article  CAS  Google Scholar 

  • WHO (2003) Benzene in drinking-water. Background document for development of WHO Guidelines for Drinking-water Quality. 4pp.

  • Yan X, Qi M, Li P, Zhan Y, Shao H (2017) Apigenin in cancer therapy: anti-cancer effects and mechanisms of action. Cell Biosci 7:50. https://doi.org/10.1186/s13578-017-0179-x

    Article  CAS  Google Scholar 

Download references

Funding

This work received financial support from the Slovak Research and Development Agency (projects no. APVV-15-0296); the Scientific Grant Agency of the Ministry of Education, Science, and Sport of Slovak Republic (project VEGA 13-ENV1321-02); and Ss. Cyril and Methodius University in Skopje (project no. FVMS-IPR-02 and the deanship of Scientific Research at King Saud University project number RG-254.

Author information

Authors and Affiliations

  1. Department of Zoology and Anthropology, Constantine the Philosopher University, Tr. A. Hlinku, 949 74, Nitra, Slovak Republic

    Alexander Sirotkin, Zuzana Záhoranska & Adam Tarko

  2. Ss. Cyril and Methodius University in Skopje, Skopje, Republic of North Macedonia

    Florina Popovska-Percinic

  3. King Saud University, Department of Zoology, College of Science, Riyadh, 11451, Saudi Arabia

    Saleh Alwasel & Abdel Halim Harrath

  4. Higher Institute of Applied Biological Sciences of Tunis, University of Tunis El Manar, 2092, Tunis, Tunisia

    Abdel Halim Harrath

Authors
  1. Alexander Sirotkin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zuzana Záhoranska
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Adam Tarko
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Florina Popovska-Percinic
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Saleh Alwasel
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Abdel Halim Harrath
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alexander Sirotkin.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Additional information

Responsible Editor: Mohamed M. Abdel-Daim

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sirotkin, A., Záhoranska, Z., Tarko, A. et al. Plant isoflavones can prevent adverse effects of benzene on porcine ovarian activity: an in vitro study. Environ Sci Pollut Res 27, 29589–29598 (2020). https://doi.org/10.1007/s11356-020-09260-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11356-020-09260-8

Keywords

Search

Navigation