Skip to main content
Log in

Furan induced ovarian damage in non-diabetic and diabetic rats and cellular protective role of lycopene

  • Images in Obstetrics and Gynecology
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

In our work, furan, lycopene, and furan + lycopene treatments were applied to non-diabetic and diabetic female rats via gavage.

Methods

Ovarian tissue alterations with histopathology, immunohistochemistry, malondialdehyde levels, oxidative stress parameters such as superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and harmful effect on ovarian tissue DNA were evaluated in all groups for 28 days.

Results

Furan caused the changes histological, ovarian cell’s DNA structure, malondialdehyde levels, antioxidant enzymes activities as in a statistically significant manner in each group. Useful effect of lycopene was determined both in non-diabetic and diabetic treatment groups against furan according to the used experimental parameters. Although some histopathological alterations were seen in diabetic and non-diabetic/diabetic plus furan-treated group’s ovarians, lycopene restored these variations near to normal levels in furan + lycopene treated groups for in 28 days. Additionally, the results of our immunohistochemical analysis and alterations of the oxidative stress parameters results also supported these findings.

Conclusions

Our result confirms that lycopene has protective effect and significantly altered diabetes and furan-induced toxicity in the rat ovarian tissue.

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

Similar content being viewed by others

References

  1. IARC (International Agency for Research on Cancer) (1995a) IARC monographs on the evaluation of carcinogenic risks to humans, dry cleaning, some chlorinated solvents and other industrial chemicals, vol 63. France, Lyon, pp 3194–3407

  2. Moro S, Chipman JK, Wegener JW, Hamberger C, Dekant W, Mally A (2012) Furan in heat-treated foods: formation, exposure, toxicity, and aspects of risk assessment. Mol Nutr Food Res 56:1197–1211

    Article  CAS  PubMed  Google Scholar 

  3. Hamadeh HK, Jayadev S, Gaillard ET, Huang Q, Stoll R, Blanchard K (2004) Integration of clinical and gene expression endpoints to explore furan-mediated hepatotoxicity. Mutat Res 549:169–183

    Article  CAS  PubMed  Google Scholar 

  4. Maga JA, Katz I (1979) Furans in foods. Crit Rev Food Sci Nutr 11:355–400

    Article  CAS  Google Scholar 

  5. IARC (International Agency for Research on Cancer) (1995b) Dry cleaning, furan. In: IARC monographs on the evaluation of carcinogenic risks to humans, some chlorinated solvents and other industrial chemicals, vol 63. France, Lyon, pp 393–407

  6. Pandır D (2015) Assesment of the DNA damage in human sperm and lymphocytes exposed to the carcinogen food contaminant furan with comet assay. Braz Arch Biol Technol 58:773–780

    Article  Google Scholar 

  7. Pandır D (2015) Protective effect of (-)-epigallocatechin-3-gallate on capsaicin-induced DNA damage and oxidative stress in human erythrocytes and leucocytes in vitro. Cytotechnology 67(2):367–377

    Article  PubMed  Google Scholar 

  8. Cooke GM, Taylor M, Bourque C, Curran I, Gurofsky S, Gill S (2014) Effects of furan on male rat reproduction parameters in a 90-day gavage study. Reprod Toxicol 46:85–90

    Article  CAS  PubMed  Google Scholar 

  9. Farokhi F, Farkhad NK, Togmechi A, Soltani K (2012) Preventive effects of Prangos ferulacea (L.) Lindle on liver damage of diabetic rats induced by alloxan. Avicenna J Phytomed 2:63–71

    PubMed  PubMed Central  Google Scholar 

  10. Bas H, Pandır D (2016) Protective effects of lycopene on furan-treated diabetic and non-diabetic rat lung. Biomed Environ Sci 29:143–147

    PubMed  Google Scholar 

  11. Unal B, Pandir D, Bas H (2016) Lycopene protects the diabetic rat kidney against oxidative stress-mediated oxidative damage induced by furan. Braz Arc Biol Technol 59:e16150794 (January–December 1–12)

    Google Scholar 

  12. Atessahin A, Karahan I, Türk G, Gür S, Yılmaz S, Ceribası 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  PubMed  Google Scholar 

  13. Bas H, Kara O, Kara M, Pandır D (2013) Protective effect of vardenafil on ischemia-reperfusion injury in rat ovary. Turk J Med Sci 43(5):684–689

    Article  CAS  Google Scholar 

  14. Leonard SS, Xia C, Jiang BH, Stinefelt B, Klandorf H, Harris GK, Shi X (2003) Resveratrol scavenges reactive oxygen species and effects radical-induced cellular responses. BBRC 309:1017–1026

    CAS  PubMed  Google Scholar 

  15. Schmatz R, Mazzanti CM, Spanevello R, Stefanello N, Gutierres J, Corrêa M (2009) Resveratrol prevents memory deficits and the increase in acetylcholinesterase activity in streptozotocin-induced diabetic rats. Eur J Pharmacol 610:42–48

    Article  CAS  PubMed  Google Scholar 

  16. Babu PVA, Liu D, Gilbert ER (2013) Recent advances in understanding the anti-diabetic actions of dietary flavonoids. J Nutr Biochem 24:1777–1789

    Article  CAS  PubMed  Google Scholar 

  17. Yin W, Li B, Li X, Yu F, Cai Q, Zhang Z, Cheng M, Gao H (2015) Anti-inflammatory effects of grape seed procyanidin B2 on a diabetic pancreas. Food Funct 6:3065–3071

    Article  CAS  PubMed  Google Scholar 

  18. Elosta T, Ghous N, Ahmed N (2012) Natural products as anti-glycation agents: possible therapeutic potential for diabetic complications. Curr Diabetes Rev 8:92–108

    Article  CAS  PubMed  Google Scholar 

  19. Coskun O, Kanter M, Korkmaz A, Oter S (2005) Quercetin: a flavonoid antioxidant, prevents and protects streptozotocin-induced oxidative stress and b-cell damage in rat pancreas. Pharmacol Res 51:117–123

    Article  CAS  PubMed  Google Scholar 

  20. Rashid K, Sil PC (2015) Curcumin enhances recovery of pancreatic islets from cellular stress induced inflammation and apoptosis in diabetic rats. Toxicol Appl Pharmacol 282:297–310

    Article  CAS  PubMed  Google Scholar 

  21. Olive PL, Banáth JP (2006) The comet assay: a method to measure DNA damage in individual cells. Nat Protoc 1:23–29

    Article  CAS  PubMed  Google Scholar 

  22. Forchhammer L, Ersson C, Loft S, Moller L, Godschalk RW, Van Schooten FJ (2012) Inter-laboratory variation in DNA damage using a standard comet assay protocol. Mutagenesis 27:65–672

    Article  Google Scholar 

  23. Amaeze NH, Schnell S, Sozeri O, Otitoloju AA, Egonmwan RI, Arlt VM, Bury NR (2015) Cytotoxic and genotoxic responses of the RTgill-W1 fish cells in combination with the yeast oestrogen screen to determine the sediment quality of Lagos lagoon. Niger Mutagen 30:117–127

    Article  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  25. 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 474:469–474

    Article  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  27. Paglia DE, Valentine WN (1967) Studies on the quantitative and qualitative characterization of glutathione peroxidase. J Lab Clin Med 70:158–169

    CAS  PubMed  Google Scholar 

  28. 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  PubMed  Google Scholar 

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

    Google Scholar 

  30. Ozkan D, Yuzbasıoglu D, Unal F, Yılmaz S, Aksoy H (2009) Evaluation of the cytogenetic damage induced by the organophosphorous insecticide acephate. Cytotechnology 59:73–80

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Behravan J, Mosafa F, Soudmand N, Taghiabadi E, Razavi BM, Karimi G (2011) Protective effects of aqueous and ethanolic extracts of Portulaca oleracea L. aerial parts on H2O2-induced DNA damage in lymphocytes by comet assay. Acupunct Meridian Stud 4:193–197

    Article  Google Scholar 

  32. Burka LT, Washburn KD, Irwin RD (1991) Disposition of [14C] furan in the male F344 rat. J Toxicol Environ Health 34:245–257

    Article  CAS  PubMed  Google Scholar 

  33. Crews C, Castle LA (2007) Review of the occurrence, formation and analysis of furan in heat-processed foods. Trends Food Sci Technol 18:344–345

    Article  Google Scholar 

  34. Mugford CA, Carfagna MA, Kedderis GL (1997) Furan-mediated uncoupling of hepatic phosphorylation in Fisher-344 rats: an early event in cell death. Toxicol Appl Pharm 144:1–11

    Article  CAS  Google Scholar 

  35. Kedderis GL, Ploch SA (1999) The biochemical toxicology of furan. Chem Ind Inst Toxicol 1:1–8

    Google Scholar 

  36. Selmanoglu G, Karacaoglu E, Kılıc A, Kockaya EA, Akay MT (2012) Toxicity of food contaminant furan on liver and kidney of growing male rats. Environ Toxicol 27:613–622

    Article  CAS  PubMed  Google Scholar 

  37. El-Akabawy G, El-Sherif NM (2016) Protective role of garlic oil against oxidative damage induced by furan exposure from weaning through adulthood in adult rat testis. Acta Histochem 118:456–463

    Article  CAS  PubMed  Google Scholar 

  38. Letchuman GR, WanNazaimoon WM, WanMohamad WB, Chandran LR, Tee GH, Reddy GK, Stehno-Bittel L, Hamade S, Enwemeka CS (2001) The biomechanical integrity of bone in experimental diabetes. Diabetes Res Clin Pract 54:1–8

    Google Scholar 

  39. Shaw JE, Sicree RA, Zimmet PZ (2010) Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract 87:4–14

    Article  CAS  PubMed  Google Scholar 

  40. Shi Y, Vanhoutte PM (2008) Oxidative stress and COX cause hyper-responsiveness in vascular smooth muscle of the femoral artery from diabetic rats. Br J Pharmacol 154:639–651

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Rerup CC (1970) Drugs producing diabetes through damage of the insulin secreting cells. Pharmacol Rev 22:485–518

    CAS  PubMed  Google Scholar 

  42. Black CT, Hennessey PJ, Ford EG, Andrassy RJ (1989) Protein glycosylation and collagen metabolism in normal and diabetic rats. J Surg Res 47:200–202

    Article  CAS  PubMed  Google Scholar 

  43. Chang K, Uitto J, Rowold EA, Grant GA, Kilo C, Williamson JR (1980) Increased collagen cross-linkages in experimental diabetes: reversal by beta-aminopropionitrile and d-penicillamine. Diabetes 29:778–781

    Article  CAS  PubMed  Google Scholar 

  44. Spanheimer RG (1989) Collagen production in bone and cartilage after short-term exposure to streptozotocin. Matrix 9:172–174

    Article  CAS  PubMed  Google Scholar 

  45. Spanheimer RG (1988) Direct inhibition of collagen production in vitro by diabetic rat serum. Metabolism 37:479–485

    Article  CAS  PubMed  Google Scholar 

  46. Spanheimer RG, Umpierrez GE, Stumpf V (1988) Decreased collagen production in diabetic rats. Diabetes 37:371–485

    Article  CAS  PubMed  Google Scholar 

  47. Ferraro E, Corvaro M, Cecconi F (2003) Physiological and pathological roles of Apaf-1 and the apoptosome. J Cell Mol Med 7(1):21–34

    Article  CAS  PubMed  Google Scholar 

  48. Hajra KM, Liu JR (2004) Apoptosome dysfunction in human cancer. Apoptosis 9(6):691–704

    Article  CAS  PubMed  Google Scholar 

  49. Robles R, Tao XJ, Trbovich AM, Maravel DV, Nahum R, Perez GI (1999) Localization regulation and possible consequences of apoptotic protease-activating factor-1 (Apaf-1) expression in granulosa cells of the mouse ovary. Endocrinology 140(6):2641–2644

    Article  CAS  PubMed  Google Scholar 

  50. Erol B, Tokgoz H, Hanci V, Bektas S, Akduman B, Yencilek F (2009) Vardenafil reduces testicular damage following ischemia/reperfusion injury in rats. Kaohsiung J Med Sci 25(7):374–380

    Article  CAS  PubMed  Google Scholar 

  51. 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 7:905–958

    Article  Google Scholar 

  52. 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  PubMed  Google Scholar 

  53. 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  PubMed  Google Scholar 

  54. 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  PubMed  Google Scholar 

  55. 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  PubMed  Google Scholar 

  56. Evans MD, Cooke MS (2004) Factors contributing to the outcome of oxidative damage to nucleic acid. Bioassays 26:533–542

    Article  CAS  Google Scholar 

  57. Balasubramanyam M, Adaikalakoteswari A, Sameermahmood Z, Mohan V (2010) Biomarkers of oxidative stress: methods and measures of oxidative DNA damage (COMET assay) and telomere shortening. Methods Mol Biol 610:245–261

    Article  CAS  PubMed  Google Scholar 

  58. Blasiak J, Arabski M, Krupa R, Wozniak K, Zadrozny M, Kasznicki J, Zurawska M, Drzewoski J (2004) DNA damage and repair in type 2 diabetes mellitus. Mutat Res 554:297–304

    Article  CAS  PubMed  Google Scholar 

  59. Park KS, Kim JH, Kim MS, Kim JM, Kim SK, Choi JY (2001) Effects of insulin and antioxidant on plasma 8-hydroxyguanine and tissue 8-hydroxydeoxyguanosine in streptozotocin-induced diabetic rats. Diabetes 50:2837–2841

    Article  CAS  PubMed  Google Scholar 

  60. Xu GW, Yao QH, Weng QF, Su BL, Zhang X, Xiong JH (2004) Study of urinary 8-hydroxydeoxyguanosine as a biomarker of oxidative DNA damage in diabetic nephropathy patients. J Pharm Biomed Anal 36:101–104

    Article  CAS  PubMed  Google Scholar 

  61. Collins AR, Dusinska M, Gedik CM, Stetina R (1996) Oxidative damage to DNA: do we have a reliable biomarker? Environ Health Perspect 104:465–469

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

DP: manuscript writing, SU: manuscript editing, and DP: manuscript editing.

Corresponding author

Correspondence to Dilek Pandir.

Ethics declarations

Funding

This work was supported by the Bozok University Scientific Research Projects Unit by the code 6601-FBE/16-38.

Conflict of interest

All authors declare that there is no conflict of interest.

Ethical approval

Female Wistar–Albino rats (300–320 g) were administrated according to standard protocol for use and care of laboratory animals. Çukurova University Animal Experiments Local Ethics Committee approved our treatment procedure (11/1).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Uçar, S., Pandir, D. Furan induced ovarian damage in non-diabetic and diabetic rats and cellular protective role of lycopene. Arch Gynecol Obstet 296, 1027–1037 (2017). https://doi.org/10.1007/s00404-017-4521-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00404-017-4521-7

Keywords

Navigation