Skip to main content
SpringerLink
Log in

Protective effect of combined pumpkin seed and ginger extracts on sperm characteristics, biochemical parameters and epididymal histology in adult male rats treated with cyclophosphamide

  • Original Article
  • Published:
Anatomical Science International Aims and scope Submit manuscript

Abstract

Reproductive toxicity is one of the side effects of cyclophosphamide (CP) in cancer treatment. Pumpkin seeds and Zingiber officinale are natural sources of antioxidants. We investigated the possible protective effect of combined pumpkin seed and Zingiber officinale extracts on sperm characteristics, epididymal histology and biochemical parameters of CP-treated rats. Male adult Wistar rats were divided randomly into six groups. Group 1, as a control, received an isotonic saline solution injection intraperitoneally (IP). Group 2 were injected IP with a single dose of CP (100 mg/kg) once. Groups 3 and 4 received CP plus 300 and 600 mg/kg combined pumpkin seed and Zingiber officinale extract (50:50). Groups 5 and 6 received only 300 and 600 mg/kg combined pumpkin seed and Zingiber officinale extract. Six weeks after treatment, sperm characteristics, histopathological changes and biochemical parameters were assessed. In CP-treated rats, motile spermatozoa were decreased, and abnormal or dead spermatozoa increased significantly (P < 0.001) but administration of the mixed extract improved sperm parameters. Epididymal epithelium and fibromascular thickness were also improved in extract-treated rats compared to control or CP groups. Biochemical analysis showed that the administration of combined extracts could increase the total antioxidant capacity (TAC) level significantly in groups 3, 4, 5 and 6. Interestingly, the mixed extract could decrease most of the side effects of CP such as vacuolization and separation of epididymal tissue. Our findings indicated that the combined extracts might be used as a protective agent against CP-induced reproductive toxicity.

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

Similar content being viewed by others

References

  • Agarwal A, Saleh RA (2002) Role of oxidants in male infertility: rationale, significance, and treatment. Urol Clin North Am 29:817–827

    Article  PubMed  Google Scholar 

  • Agarwal A, Sharma RK, Desai NR, Prabakaran S, Tavares A, Sabanegh E (2009) Role of oxidative stress in pathogenesis of varicocele and infertility. Urology 73:461–469

    Article  PubMed  Google Scholar 

  • Aghaei S, Nikzad H, Taghizadeh M, Tameh A, Taherian A, Moravveji A (2014) Protective effect of pumpkin seed extract on sperm characteristics, biochemical parameters and epididymal histology in adult male rats treated with cyclophosphamide. Andrologia 46:927–935

    Article  CAS  PubMed  Google Scholar 

  • Ajayi IA, Oderinde RA, Taiwo VO, Agbedana EO (2004) Dietary effects on growth, plasma lipid and tissues of rats fed with non-conventional oil of Telfairia occidentalis. J Sci Food 84:1715–1721

    Article  CAS  Google Scholar 

  • Akang E, Oremosu A, Dosumu O, Noronha C, Okanlawon A (2010) The effect of fluted pumpkin (Telferia occidentalis) seed oil (FPSO) on testis and semen parameters. Agr Biol J North 1:697–703

    CAS  Google Scholar 

  • Akbarsha M, Latha P, Murugaian P (2000) Retention of cytoplasmic droplet by rat cauda epididymal spermatozoa after treatment with cytotoxic and xenobiotic agents. J Reprod Fertil 120:385–390

    Article  CAS  PubMed  Google Scholar 

  • Akwaowo EU, Ndon BA, Etuk EU (2000) Minerals and antinutrients in fluted pumpkin (Telfairia occidentalis Hook f.). Food Chem 70:235–240

    Article  CAS  Google Scholar 

  • Anderson D, Bishop JB, Garner RC, Ostrosky-Wegman P, Selby PB (1995) Cyclophosphamide: review of its mutagenicity for an assessment of potential germ cell risks. Mutat Res 330:115–181

    Article  CAS  PubMed  Google Scholar 

  • Bensoussan K, Morales CR, Hermo L (1998) Vitamin E deficiency causes incomplete spermatogenesis and affects the structural differentiation of epithelial cells of the epididymis in the rat. J Androl 19:266–288

    CAS  PubMed  Google Scholar 

  • Bourre JM, Dumont O, Durand G (2004) Dose-effect of dietary oleic acid: oleic acid is conditionally essential for some organs. Reprod Nutr Dev 44:371–380

    Article  CAS  PubMed  Google Scholar 

  • Cai L, Hales BF, Robaire B (1997) Induction of apoptosis in the germ cells of adult male rats after exposure to cyclophosphamide. Biol Reprod 56:1490–1497

    Article  CAS  PubMed  Google Scholar 

  • Ceribasi AO, Turk G, Sonmez M, Sakin F, Atessahin A (2010) Toxic effect of cyclophosphamide on sperm morphology, testicular histology and blood oxidant-antioxidant balance, and protective roles of lycopene and ellagic acid. Basic Clin Pharmacol Toxicol 107:730–736

    Article  CAS  PubMed  Google Scholar 

  • Chrubasik S, Pittler M, Roufogalis B (2005) Zingiberis rhizoma: a comprehensive review on the ginger effect and efficacy profiles. Phytomedicine 12:684–701

    Article  CAS  PubMed  Google Scholar 

  • Codrington A, Hales B, Robaire B (2007) Exposure of male rats to cyclophosphamide alters the chromatin structure and basic proteome in spermatozoa. Hum Reprod 22:1431–1442

    Article  CAS  PubMed  Google Scholar 

  • Cornwall GA, Horsten V, Henning H, Swartz D, Johnson S, Chau K et al (2007) Extracellular quality control in the epididymis. Asian J Androl 9:500–507

    Article  CAS  PubMed  Google Scholar 

  • Djeridane A, Yousfi M, Nadjemi B, Boutassouna D, Stocker P, Vidal N (2006) Antioxidant activity of some Algerian medicinal plants extracts containing phenolic compounds. Food Chem 97:654–660

    Article  CAS  Google Scholar 

  • Egbunike GN, Branscheid W, Pfisterer J, Holtz W (1986) Changes in porcine sperm lactate dehydrogenase isoenzymes during sperm maturation. Andrologia 18:108–113

    Article  CAS  PubMed  Google Scholar 

  • Elangovan N, Chiou T-J, Tzeng W-F, Chu S-T (2006) Cyclophosphamide treatment causes impairment of sperm and its fertilizing ability in mice. Toxicology 222:60–70

    Article  CAS  PubMed  Google Scholar 

  • Fadillioglu E, Erdogan H (2003) Effects of erdosteine treatment against doxorubicin-induced toxicity through erythrocyte and plasma oxidant/antioxidant status in rats. Pharmacol Res 47:317–322

    Article  CAS  PubMed  Google Scholar 

  • Fruhwirth GO, Hermetter A (2007) Seeds and oil of the Styrian oil pumpkin: components and biological activities. Eur J Lipid Sci Technol 109:1128–1140

    Article  CAS  Google Scholar 

  • Gatti J-L, Castella S, Dacheux F, Ecroyd H, Metayer S, Thimon V et al (2004) Post-testicular sperm environment and fertility. Anim Reprod Sci 82:321–339

    Article  PubMed  Google Scholar 

  • Ghiselli A, Serafini M, Natella F, Scaccini C (2000) Total antioxidant capacity as a tool to assess redox status: critical view and experimental data. Free Radic Biol Med 29:1106–1114

    Article  CAS  PubMed  Google Scholar 

  • Gossell-Williams M, Davis A, O’connor N (2006) Inhibition of testosterone-induced hyperplasia of the prostate of Sprague-Dawley rats by pumpkin seed oil. J Med Food 9:284–286

    Article  CAS  PubMed  Google Scholar 

  • Hafez DA (2010) Effect of extracts of ginger goots and cinnamon bark on fertility of male diabetic rats. J Am Sci 6:940–947

    Google Scholar 

  • Hoorweg-Nijman JJ, Delemarre-Van De Waal HA, De Waal FC, Behrendt H (1992) Cyclophosphamide-induced disturbance of gonadotropin secretion manifesting testicular damage. Acta Endocrinol 126:143–148

    CAS  PubMed  Google Scholar 

  • Ilbey YO, Ozbek E, Simsek A, Otunctemur A, Cekmen M, Somay A (2009) Potential chemoprotective effect of melatonin in cyclophosphamide- and cisplatin-induced testicular damage in rats. Fertil Steril 92:1124–1132

    Article  CAS  PubMed  Google Scholar 

  • Kamtchouing P, Fandio GM, Dimo T, Jatsa HB (2002) Evaluation of androgenic activity of Zingiber officinale and Pentadiplandra brazzeana in male rats. Asian J Androl 4:299–302

    PubMed  Google Scholar 

  • Kanno TYN, Sensiate LA, NaD Paula, Salles MJS (2009) Toxic effects of different doses of cyclophosphamide on the reproductive parameters of male mice. Braz J Pharm Sci 45:313–319

    Article  CAS  Google Scholar 

  • Khaki A, Farnam A, Badie AD, Nikniaz H (2012) Treatment effects of onion (Allium cepa) and ginger (Zingiber officinale) on sexual behavior of rat after inducing an antiepileptic drug (lamotrigine). Balkan Med J 29:236–242

    PubMed  PubMed Central  Google Scholar 

  • Khanom F, Kayahara H, Hirota M, Tadasa K (2003) Superoxide scavenging and tyrosinase inhibitory active compound in ginger (Zingiber officinale Roscoe). Pakistan J Biol Sci 6:1996–2000

    Article  Google Scholar 

  • Kreft I, Stibilj V, Trkov Z (2002) Iodine and selenium contents in pumpkin (Cucurbita pepo L.) oil and oil-cake. Eur Food Res Technol 215:279–281

    Article  CAS  Google Scholar 

  • Lachance C, Fortier M, Thimon V, Sullivan R, Bailey JL, Leclerc P (2010) Localization of Hsp60 and Grp78 in the human testis, epididymis and mature spermatozoa. Int J Androl 33:33–44

    Article  CAS  PubMed  Google Scholar 

  • Lazos ES (1986) Nutritional, fatty acid, and oil characteristics of pumpkin and melon seeds. J Food Sci 51:1382–1383

    Article  CAS  Google Scholar 

  • Lear L, Nation RL, Stupans I (1992) Effects of cyclophosphamide and adriamycin on rat hepatic microsomal glucuronidation and lipid peroxidation. Biochem Pharmacol 44:747–753

    Article  CAS  PubMed  Google Scholar 

  • Leat WM, Northrop CA, Harrison FA, Cox RW (1983) Effect of dietary linoleic and linolenic acids on testicular development in the rat. Q J Exp Physiol 68:221–231

    Article  CAS  PubMed  Google Scholar 

  • Lovejoy JC (2002) The influence of dietary fat on insulin resistance. Curr Diab Rep 2:435–440

    Article  PubMed  Google Scholar 

  • Lu W-P, Mei X-T, Wang Y, Zheng Y-P, Xue Y-F, Xu D-H (2015) Zn (II)–curcumin protects against oxidative stress, deleterious changes in sperm parameters and histological alterations in a male mouse model of cyclophosphamide-induced reproductive damage. Environ Toxicol Phar 39:515–524

    Article  CAS  Google Scholar 

  • Mohan H, Verma J, Singh I, Mohan P, Marwah S, Singh P (1997) Inter-relationship of zinc levels in serum and semen in oligospermic infertile patients and fertile males. Indian J Pathol Microbiol 40:451–455

  • Murakami A, Takahashi D, Kinoshita T, Koshimizu K, Kim HW, Yoshihiro A et al (2002) Zerumbone, a Southeast Asian ginger sesquiterpene, markedly suppresses free radical generation, proinflammatory protein production, and cancer cell proliferation accompanied by apoptosis: the α, β-unsaturated carbonyl group is a prerequisite. Carcinogenesis 23:795–802

    Article  CAS  PubMed  Google Scholar 

  • Nkang A, Omokaro D, Egbe A, Amanke G (2004) Variations in fatty acid proportions during desiccation of Telfairia occidentalis seeds harvested at physiological and agronomic maturity. Afr J Biotechnol 2:33–39

    Article  Google Scholar 

  • Poblador MS, Rojas C, Raya A, Casares JA, Aparicio J, Lancho Alonso JL (1990) The effects of cyclophosphamide on the gonadotrophic cells of the normal rat. Histol Histopathol 5:173–180

    CAS  PubMed  Google Scholar 

  • Pyy L, Sorsa M, Hakala E (1988) Ambient monitoring of cyclophosphamide in manufacture and hospitals. Am Ind Hyg Assoc J 49:314–317

    Article  CAS  PubMed  Google Scholar 

  • Salmon CN, Bailey-Shaw YA, Hibbert S, Green C, Smith AM, Williams LA (2012) Characterisation of cultivars of Jamaican ginger (Zingiber officinale Roscoe) by HPTLC and HPLC. Food Chem 131:1517–1522

    Article  CAS  Google Scholar 

  • Selvakumar E, Prahalathan C, Mythili Y, Varalakshmi P (2005) Mitigation of oxidative stress in cyclophosphamide-challenged hepatic tissue by dl-α-lipoic acid. Mol Cell Biochem 272:179–185

    Article  CAS  PubMed  Google Scholar 

  • Selvakumar E, Prahalathan C, Sudharsan PT, Varalakshmi P (2006) Chemoprotective effect of lipoic acid against cyclophosphamide-induced changes in the rat sperm. Toxicology 217:71–78

    Article  CAS  PubMed  Google Scholar 

  • Shukla Y, Singh M (2007) Cancer preventive properties of ginger: a brief review. Food Chem Toxicol 45:683–690

    Article  CAS  PubMed  Google Scholar 

  • Stevenson DG, Eller FJ, Wang L, Jane JL, Wang T, Inglett GE (2007) Oil and tocopherol content and composition of pumpkin seed oil in 12 cultivars. J Agr Food Chem 55:4005–4013

    Article  CAS  Google Scholar 

  • Tripathi D, Jena G (2008) Astaxanthin inhibits cytotoxic and genotoxic effects of cyclophosphamide in mice germ cells. Toxicology 248:96–103

    Article  CAS  PubMed  Google Scholar 

  • Tsai YS, Tong YC, Cheng JT, Lee CH, Yang FS, Lee HY (2006) Pumpkin seed oil and phytosterol-F can block testosterone/prazosin-induced prostate growth in rats. Urol Int 77:269–274

    Article  CAS  PubMed  Google Scholar 

  • Tsantili E, Shin Y, Nock JF, Watkins CB (2010) Antioxidant concentrations during chilling injury development in peaches. Postharvest Biol Technol 57:27–34

    Article  CAS  Google Scholar 

  • Vartsky D, Shilstein S, Bercovich A, Huszar M, Breskin A, Chechik R et al (2003) Prostatic zinc and prostate specific antigen: an experimental evaluation of their combined diagnostic value. J Urol 170:2258–2262

    Article  CAS  PubMed  Google Scholar 

  • Velez De La Calle J, Queiroz FD, Garnier D, Kercret H, Folliot R, Jegou B (1989) Reproductive effects of the anticancer drug cyclophosphamide in male rats at different ages. Syst Biol Reprod Med 22:251–263

    CAS  Google Scholar 

  • Vernet P, Aitken RJ, Drevet JR (2004) Antioxidant strategies in the epididymis. Mol Cell Endocrinol 216:31–39

    Article  CAS  PubMed  Google Scholar 

  • WHO (2010) World Health Organization Laboratory manual for the examination and processing of human semen, 5th edn. World Health Organization Press, Geneva

    Google Scholar 

Download references

Acknowledgments

This study was supported financially by the deputy of research in Kashan University of Medical Sciences and Kashan Anatomical Sciences Research Center (Grant No 9110). The authors gratefully acknowledge the kind cooperation of all staff in the Anatomical Sciences Research Center, Kashan University of Medical Science.

Author information

Authors and Affiliations

  1. Anatomical Sciences Research Center, Kashan University of Medical Science, Kashan, Iran

    Somaieh Aghaie, Abolfazl Azami-Tameh, Aliakbar Taherian & Mehran Kamani

  2. Gametogenesis Research Center, Kashan University of Medical Sciences, Kashan, Iran

    Hossein Nikzad & Javad Amini Mahabadi

  3. Research Center for Biochemistry and Nutrition in Metabolic Disorders, Kashan University of Medical Science, Kashan, Iran

    Mohsen Taghizadeh

  4. Student Research Committee, Kashan University of Medical Science, Kashan, Iran

    Seyyed Mohammad Sajjad Sajjadian

Authors
  1. Somaieh Aghaie
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hossein Nikzad
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Javad Amini Mahabadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mohsen Taghizadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Abolfazl Azami-Tameh
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Aliakbar Taherian
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Seyyed Mohammad Sajjad Sajjadian
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mehran Kamani
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hossein Nikzad.

Ethics declarations

Conflict of interest

The authors have no conflicts of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Aghaie, S., Nikzad, H., Mahabadi, J.A. et al. Protective effect of combined pumpkin seed and ginger extracts on sperm characteristics, biochemical parameters and epididymal histology in adult male rats treated with cyclophosphamide. Anat Sci Int 91, 382–390 (2016). https://doi.org/10.1007/s12565-015-0314-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12565-015-0314-x

Keywords

Search

Navigation