Skip to main content
Log in

Protective effect of bilberry (Vaccinium myrtillus L.) on cisplatin induced ovarian damage in rat

  • Original Research
  • Published:
Cytotechnology Aims and scope Submit manuscript

Abstract

Cisplatin is one of the most effective chemotherapeutic agents but injury may occur at higher doses. The aim of this study was to investigate the effect of bilberry on cisplatin induced toxic effects in rat ovary. Twenty-one female Wistar–Albino rats were utilized to form three groups: In group 1 (control group), each rat received intraperitoneal injection of 1 mL of 0.9 % NaCl saline solution during 10-days. In group 2 (cisplatin group), a single dose of 7.5 mg/kg b.w. cisplatin was given. In group 3 (cisplatin + bilberry group), a single dose of 7.5 mg/kg cisplatin and bilberry at 200 mg/kg b.w. were given for 10 days. Ovaries were surgically removed in all groups and prepared for biochemical and light microscopic investigations at the examination times. Malondialdehyde (MDA) levels and activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) of tissue samples were measured. Histopathological damages in cisplatin administrated rats were seen such as severe edema, vascular congestion, hemorrhage and follicular degeneration in the ovary tissue. Moderate pathological alterations were observed in rats treated with bilberry plus cisplatin. Cisplatin administration significantly increased MDA production and decreased SOD, CAT, GPx and GST activities in the ovarian tissue when compared to the control group (p < 0.05). Cisplatin + bilberry administration increased antioxidant enzymes activities and reduced MDA levels. Bilberry administration seems to reduce the cisplatin induced ovarian toxicity thus it alleviates free radical damage. But it dose not protect completely rat ovary tissues.

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

Access this article

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
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  • Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126

    Article  CAS  Google Scholar 

  • Altuner D, Gulaboglu M, Yapca OE, Cetin N (2013) The effect of mirtazapine on cisplatin-induced oxidative damage and infertility in rat ovaries. Sci World J 2013:Article ID 3272240, 6

  • Atessahin A, Karahan I, Turk G, Gur S, Yilmaz S, Ceribasi AO (2006) Protective role of lycopene on cisplatin-induced changes in sperm characteristics testicular damage and oxidative stress in rats. Reprod Toxicol 21:42–47

    Article  CAS  Google Scholar 

  • Attia SM (2012) Influence of resveratrol on oxidative damage in genomic DNA and apoptosis induced by cisplatin. Mutat Res 741:22–31

    Article  CAS  Google Scholar 

  • Bao L, Yao XS, Yau CC, Tsi D, Chia CS, Nagai H, Kurihara H (2008a) Protective effects of Bilberry (Vaccinium myrtillus L.) extract on restraint stress-induced liver damage in mice. J Agric Food Chem 56:7803–7807

    Article  CAS  Google Scholar 

  • Bao L, Yao XS, Tsi D (2008b) Protective effects of Bilberry (Vaccinium myrtillus L.) extract on KBrO3-induced kidney damage in mice. J Agric Food Chem 56:420–425

    Article  CAS  Google Scholar 

  • Bell DR, Gochenaur K (2006) Direct vasoactive and vasoprotective properties of anthocyanin-rich extracts. Appl Physiol 100:1164–1170

    Article  CAS  Google Scholar 

  • Bodiga VL, Bodiga S, Surampudi S, Boindala S, Putcha U, Nagalla B, Subramaniam K, Manchala R (2012) Effect of vitamin supplementation on cisplatin-induced intestinal epithelial cell apoptosis in Wistar/NIN rats. Nutrition 28:572–580

    Article  CAS  Google Scholar 

  • Borovskaya TG, Goldberg VE, Fomina TI, Pakhomova AV, Kseneva SI, Poluektova ME, Goldberg ED (2004) Morphological and functional state of rat ovaries in early and late periods after administration of platinum cytostatics. Bull Exp Biol Med 137:31–335

    Article  Google Scholar 

  • Boulikas T, Vougiouka M (2003) Cisplatin and platinum drugs at the molecular level (review). Oncol Rep 10:1663–1682

    CAS  Google Scholar 

  • Caffrey PB, Frenkel GD (2000) Selenium compounds prevent the induction of drug resistance by cisplatin in human ovarian tumor xenografts in vivo. Cancer Chemother Pharmacol 46:74–78

    Article  CAS  Google Scholar 

  • Carter S (1984) Cisplatin-past present and future. In: Hacker MP (ed) Platinum coordination complexes in cancer chemotherapy. Martinus Nijhoff Press, Boston, pp 359–376

    Chapter  Google Scholar 

  • Celik I, Suzek H (2009) Effects of subacute exposure of dichlorvos at sublethal dosages on erythrocyte and tissue antioxidant defense systems and lipid peroxidation in rats. Ecotoxicol Environ Saf 72:905–958

    Article  CAS  Google Scholar 

  • Cepeda V, Fuertes MA, Castilla J, Alonso C, Quevedo C, Perez JM (2007) Biochemical mechanisms of cisplatin cytotoxicity. Anticancer Agents Med Chem 7:3–18

    Article  CAS  Google Scholar 

  • Choi SJ, Kim SW, Lee JB, Lim HJ, Kim YJ, Tian C, So HS, Park R, Choung YH (2013) Gingko biloba extracts protect auditory hair cells from cisplatin-induced ototoxicity by inhibiting perturbation of gap junctional intercellular communication. Neuroscience 244:49–61

    Article  CAS  Google Scholar 

  • DeVita VT, Hellman S, Rosenberg SA (2005) Cancer: principals and practice of oncology, 7th edn. Lippincott Williams & Wilkins, Philadelphia, PA

    Google Scholar 

  • Dillioglugil MO, Maral KH, Gulkac MD, Ozon KA, Ozdogan HK, Acar O, Dillioglugil O (2005) Protective effects of increasing vitamin E and a doses on cisplatin-induced oxidative damage to kidney tissue in rats. Urol Int 75:340–344

    Article  CAS  Google Scholar 

  • Dixit M, Yang JL, Poirier MC, Price JO, Andrews PA, Arteaga CL (1997) Abrogation of cisplatin induced programmed cell death in human breast cancer cells by epidermal growth factor antisense RNA. J Natl Cancer Inst 89:365–373

    Article  CAS  Google Scholar 

  • Durak D, Uzun FG, Kalender S, Ogutcu A, Uzunhisarcikli M, Kalender Y (2009) Malathion-induced oxidative stress in human erythrocytes and the protective effect of vitamins C and E in vitro. Environ Toxicol 24:235–242

    Article  CAS  Google Scholar 

  • Goiffon JP, Brun M, Bourrier MJ (1991) High-performance liquid chromatography of red fruit anthocyanins. J Chromatogr A 537:101–121

    Google Scholar 

  • Gupta RK, Schuh RA, Fiskum G, Flaws JA (2006) Methoxychlor causes mitochondrial dysfunction and oxidative damage in the mouse ovary. Toxicol Appl Pharmacol 216:436–445

    Article  CAS  Google Scholar 

  • Habig WH, Pabst MJ, Jakoby WB (1974) Glutathione-S-transferases: the first enzymatic step in mercapturic acid formation. J Biol Chem 249:7130–7139

    CAS  Google Scholar 

  • Ichiyanagi T, Yoshihiko H, Matsuo S, Konishi T (2004) Simultaneous comparison of relative reactivities of twelve major anthocyanins in bilberry towards reactive nitrogen species. Chem Pharm Bull 52:1312–1315

    Article  CAS  Google Scholar 

  • Jakesevic M, Aaby K, Borge GIA, Jeppsson B, Ahrne S, Molin G (2011) Antioxidative protection of dietary bilberry chokeberry and Lactobacillus plantarum HEAL19 in mice subjected to intestinal oxidative stress by ischemia-reperfusion. BMC Complement Altern Med 1:11–12

    Google Scholar 

  • Jang YP, Zhou J, Nakanishi K, Sparrow RJ (2005) Anthocyanins protect against A2E photooxidation and membrane permeabilization in retinal pigment epithelial cell. Photochem Photobiol 8:529–536

    Article  Google Scholar 

  • Kara M, Daglioglu YK, Kuyucu Y, Tuli A, Tap A (2012) The effect of edaravone on ischemia–reperfusion injury in rat ovary. Eur J Obstet Gynecol Reprod Biol 162:197–202

    Article  CAS  Google Scholar 

  • Kart A, Cigremis Y, Karaman M, Ozen H (2010) Caffeic acid phenethyl ester (CAPE) ameliorates cisplatin-induced hepatotoxicity in rabbit. Exp Toxicol Pathol 62:45–52

    Article  CAS  Google Scholar 

  • Kim M, Park YJ, Kim OJ, Lee GY, Chung EJ, Sung YK, Kim JC, Han I, Sohn YO (2003) Gene expression profiles related with overcoming cisplatin resistance in human cancer cell lines. Cancer Ther 1:21–29

    Google Scholar 

  • Li X, Yang S, Lv X, Sun H, Weng J, Liang Y, Zhou D (2013) The mechanism of mesna in protection from cisplatin-induced ovarian damage in female rats. J Gynecol Oncol 24:177–185

    Article  Google Scholar 

  • Longo V, Gervasi PG, Lubrano V (2011) Cisplatin induced toxicity in rat tissues: the protective effect of Lisosan G. Food Chem Toxicol 49:233–237

    Article  CAS  Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the folin phenol reagent. J Biol Chem 19:265–275

    Google Scholar 

  • Mansour HH, Hafez HF, Fahmy NM (2006) Silymarin modulates cisplatin-induced oxidative stress and hepatotoxicity in rats. J Biochem Mol Biol 39:656–661

    Article  CAS  Google Scholar 

  • Marklund S, Marklund G (1974) Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 47:469–474

    Article  CAS  Google Scholar 

  • Matsumoto H, Hanamura S, Kawakami T, Sato Y, Hirayama MJ (2001) Preparative-scale isolation of four anthocyanin components of black currant (Ribes nigrum L.) fruits. Agric Food Chem 49:1541–1545

    Article  CAS  Google Scholar 

  • Matsuo G, Kimio U, Atsuhiko S, Takahashi S, Fujiyoshi N, Takemoto S, Terada A, Fukui A, Kamura T (2007) GnRH agonist acts as ovarian protection in chemotheraphy induced gonadotoxicity: an experiment using a rat model. Kurume Med J 54:25–29

    Article  CAS  Google Scholar 

  • Meirow D (2000) Reproduction post-chemotherapy in young cancer patients. Mol Cell Endocrinol 169:123–131

    Article  CAS  Google Scholar 

  • Milbury PE, Graf B, Curran-Celentano JM, Blumberg JB (2007) Bilberry (Vaccinium myrtillus) anthocyanins modulate heme oxygenase-1 and glutathione S-transferase-pi expression in ARPE-19 cells. IOVS 48:2343–2349

    Google Scholar 

  • Naqshbandi A, Khan W, Rizwan S, Rehman S, Khan F (2012) Studies on the protective effect of dietary fish oil on cisplatin induced nephrotoxicity in rats. Food Chem Toxicol 50:265–273

    Article  CAS  Google Scholar 

  • Nasir J, Walton C, Lindow SW, Masson EA (1997) Spontaneous recovery of chemotherapy-induced primary ovarian failure: implications for management. Clin Endocrinol (Oxf) 46:217–219

    Article  CAS  Google Scholar 

  • Naziroglu M, Karaoglu A, Aksoy AO (2004) Selenium and high dose vitamin E administration protects cisplatin-induced oxidative damage to renal liver and lens tissues in rats. Toxicology 15:221–230

    Article  Google Scholar 

  • Noori S, Mahboob T (2010) Antioxidant effect of carnosine pretreatment on cisplatin-induced renal oxidative stress in rats. Indian J Clin Biochem 25:86–91

    Article  CAS  Google Scholar 

  • Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid rection. Anal Biochem 95:351–358

    Article  CAS  Google Scholar 

  • Ozer MK, Asci H, Oncu M, Calapoglu M, Savran M, Yesilot S, Candan IA, Cicek E (2011) Effects of misoprostol on cisplatin-induced renal damage in rats. Food Chem Toxicol 49:1556–1559

    Article  CAS  Google Scholar 

  • Paglia DE, Valentine WN (1987) Studies on the quantative and qualitative characterization of glutathione peroxidase. J Lab Med 70:158–165

    Google Scholar 

  • Rodriguez C, Mayo JC, Sainz RM, Antolin I, Herrera F, Martin V, Reiter RJ (2004) Regulation of antioxidant enzymes: a significant role for melatonin. J Pineal Res 36:1–9

    Article  CAS  Google Scholar 

  • Saad SY, Najjar TA, Alashari M (2004) Role of nonselective adenosine receptor blockade and phosphodiesterase inhibition in cisplatin-induced nephrogonadal toxicity in rats. Clin Exp Pharmacol Physiol 31:862–867

    Article  CAS  Google Scholar 

  • Sasaki M, Joh T (2007) Oxidative stress and ischemia-reperfusion injury in gastrointestinal tract and antioxidant protective agents. J Clin Biochem Nutr 40:1–12

    Article  CAS  Google Scholar 

  • Satoh M, Kashihara N, Fujimoto S, Horike H, Tokura T, Namikoshi T, Sasaki T, Makino H (2003) A novel free radical scavenger edarabone protects against cisplatin-induced acute renal damage in vitro and in vivo. J Pharmacol Exp Ther 305:1183–1190

    Article  CAS  Google Scholar 

  • Sharma SK, Goyal N (2012) Protective effect of Heliotropium eichwaldi against cisplatin-induced nephrotoxicity in mice. Zhong Xi Yi Jie He Xue Bao 10:555–560

    Article  Google Scholar 

  • Stroud JS, Mutch D, Rader J, Powell M, Thaker PH, Grigsby PW (2009) Effects of cancer treatment on ovarian function. Fertil Steril 92:417–427

    Article  CAS  Google Scholar 

  • Sweetman SC (2002) The complete drug reference. Pharmaceutical Press, London

    Google Scholar 

  • Ueki M, Ueno M, Morishita J, Maekawa N (2013) Curcumin ameliorates cisplatin-induced nephrotoxicity by inhibiting renal inflammation in mice. J Biosci Bioeng 115:547–551

    Article  CAS  Google Scholar 

  • Wallace WH, Shalet SM, Crowne EC, Morris-Jones PH, Gattamaneni HR, Price DA (1989) Gonadal dysfunction due to cis-platinum. Med Pediatr Oncol 17:409–413

    Article  CAS  Google Scholar 

  • Yeh J, Kim BS, Liang YJ, Peresie J (2006) Müllerian inhibiting substance as a novel biomarker of cisplatin-induced ovarian damage. Biochem Biophys Res Commun 348:337–344

    Article  CAS  Google Scholar 

  • Yeh J, Kim BS, Peresie J (2008) Protection against cisplatin-induced ovarian damage by the antioxidant sodium 2-mercaptoethanesulfonate (mesna) in female rats. Am J Obstet Gynecol 198:463–466

    Google Scholar 

  • Yucebilgin MS, Terek MC, Ozsaran A, Akercan F, Zekioglu O, Isik E, Erhan Y (2004) Effect of chemotherapy on primordial follicular reserve of rat: an animal model of premature ovarian failure and infertility. Aust NZJ Obstet Gynaecol 44:6–9

    Article  Google Scholar 

  • Zhang Y, Wang C, Wang H, Wang K, Du Y, Zhang J (2011) Combination of tetrandrine with cisplatin enhances cytotoxicity through growth suppression and apoptosis in ovarian cancer in vitro and in vivo. Cancer Lett 304:21–32

    Article  CAS  Google Scholar 

Download references

Acknowledgments

We would like to thank Esra Guven for her help in our study.

Conflict of interest

The authors declare no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Dilek Pandir.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pandir, D., Kara, O. & Kara, M. Protective effect of bilberry (Vaccinium myrtillus L.) on cisplatin induced ovarian damage in rat. Cytotechnology 66, 677–685 (2014). https://doi.org/10.1007/s10616-013-9621-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10616-013-9621-z

Keywords

Navigation