Protective effect of combined pumpkin seed and ginger extracts on sperm characteristics, biochemical parameters and epididymal histology in adult male rats treated with cyclophosphamide
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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.
Keywords
Cyclophosphamide Pumpkin seed and Zingiber officinale extract Rat’s epididymis Sperm parameters Total antioxidant capacity (TAC)Notes
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.
Compliance with ethical standards
Conflict of interest
The authors have no conflicts of interest.
References
- Agarwal A, Saleh RA (2002) Role of oxidants in male infertility: rationale, significance, and treatment. Urol Clin North Am 29:817–827CrossRefPubMedGoogle 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 73:461–469CrossRefPubMedGoogle 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 46:927–935CrossRefPubMedGoogle 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 84:1715–1721CrossRefGoogle 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 1:697–703Google 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 120:385–390CrossRefPubMedGoogle Scholar
- Akwaowo EU, Ndon BA, Etuk EU (2000) Minerals and antinutrients in fluted pumpkin (Telfairia occidentalis Hook f.). Food Chem 70:235–240CrossRefGoogle 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 330:115–181CrossRefPubMedGoogle 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 19:266–288PubMedGoogle 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 44:371–380CrossRefPubMedGoogle 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 56:1490–1497CrossRefPubMedGoogle 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 107:730–736CrossRefPubMedGoogle Scholar
- Chrubasik S, Pittler M, Roufogalis B (2005) Zingiberis rhizoma: a comprehensive review on the ginger effect and efficacy profiles. Phytomedicine 12:684–701CrossRefPubMedGoogle 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 22:1431–1442CrossRefPubMedGoogle 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 9:500–507CrossRefPubMedGoogle 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 97:654–660CrossRefGoogle Scholar
- Egbunike GN, Branscheid W, Pfisterer J, Holtz W (1986) Changes in porcine sperm lactate dehydrogenase isoenzymes during sperm maturation. Andrologia 18:108–113CrossRefPubMedGoogle 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 222:60–70CrossRefPubMedGoogle 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 47:317–322CrossRefPubMedGoogle Scholar
- Fruhwirth GO, Hermetter A (2007) Seeds and oil of the Styrian oil pumpkin: components and biological activities. Eur J Lipid Sci Technol 109:1128–1140CrossRefGoogle 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 82:321–339CrossRefPubMedGoogle 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 29:1106–1114CrossRefPubMedGoogle 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 9:284–286CrossRefPubMedGoogle Scholar
- Hafez DA (2010) Effect of extracts of ginger goots and cinnamon bark on fertility of male diabetic rats. J Am Sci 6:940–947Google 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 126:143–148PubMedGoogle 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 92:1124–1132CrossRefPubMedGoogle 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 4:299–302PubMedGoogle 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 45:313–319CrossRefGoogle 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 29:236–242PubMedPubMedCentralGoogle 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 6:1996–2000CrossRefGoogle 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 215:279–281CrossRefGoogle 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 33:33–44CrossRefPubMedGoogle Scholar
- Lazos ES (1986) Nutritional, fatty acid, and oil characteristics of pumpkin and melon seeds. J Food Sci 51:1382–1383CrossRefGoogle Scholar
- Lear L, Nation RL, Stupans I (1992) Effects of cyclophosphamide and adriamycin on rat hepatic microsomal glucuronidation and lipid peroxidation. Biochem Pharmacol 44:747–753CrossRefPubMedGoogle 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 68:221–231CrossRefPubMedGoogle Scholar
- Lovejoy JC (2002) The influence of dietary fat on insulin resistance. Curr Diab Rep 2:435–440CrossRefPubMedGoogle 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 39:515–524CrossRefGoogle 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 40:451–455Google Scholar
- 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 23:795–802CrossRefPubMedGoogle 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 2:33–39CrossRefGoogle 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 5:173–180PubMedGoogle Scholar
- Pyy L, Sorsa M, Hakala E (1988) Ambient monitoring of cyclophosphamide in manufacture and hospitals. Am Ind Hyg Assoc J 49:314–317CrossRefPubMedGoogle 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 131:1517–1522CrossRefGoogle 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 272:179–185CrossRefPubMedGoogle Scholar
- Selvakumar E, Prahalathan C, Sudharsan PT, Varalakshmi P (2006) Chemoprotective effect of lipoic acid against cyclophosphamide-induced changes in the rat sperm. Toxicology 217:71–78CrossRefPubMedGoogle Scholar
- Shukla Y, Singh M (2007) Cancer preventive properties of ginger: a brief review. Food Chem Toxicol 45:683–690CrossRefPubMedGoogle 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 55:4005–4013CrossRefGoogle Scholar
- Tripathi D, Jena G (2008) Astaxanthin inhibits cytotoxic and genotoxic effects of cyclophosphamide in mice germ cells. Toxicology 248:96–103CrossRefPubMedGoogle 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 77:269–274CrossRefPubMedGoogle Scholar
- Tsantili E, Shin Y, Nock JF, Watkins CB (2010) Antioxidant concentrations during chilling injury development in peaches. Postharvest Biol Technol 57:27–34CrossRefGoogle 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 170:2258–2262CrossRefPubMedGoogle 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 22:251–263Google Scholar
- Vernet P, Aitken RJ, Drevet JR (2004) Antioxidant strategies in the epididymis. Mol Cell Endocrinol 216:31–39CrossRefPubMedGoogle Scholar
- WHO (2010) World Health Organization Laboratory manual for the examination and processing of human semen, 5th edn. World Health Organization Press, GenevaGoogle Scholar