Di(2-ethylhexyl) phthalate (DEHP), the most abundant phthalate in the environment, is known to be a reproductive toxicant. Considering the therapeutic significance of medicinal plants, this study was conducted to evaluate the effects of administration of celery oil on DEHP-induced testicular toxicity. The experiment was carried out for 8 weeks on 36 male rats that were divided equally into six groups. Group 1 was kept as normal control (given vehicle), while rats of group 2 were administered orally 200 mg/kg/day of celery oil. Groups 3 and 5 were orally given 500 and 1000 mg DEHP/kg/day, respectively. Groups 4 and 6 were treated with similar doses of DEHP as in groups 3 and 5 plus celery oil (200 mg/kg/day). Body and testicular weights, sperm parameters, serum hormones (testosterone, follicle-stimulating hormone, luteinizing hormone and estradiol), antioxidant enzymes (superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT)) and expression of cytochrome P450 aromatase (CYP19) messenger RNA (mRNA) were investigated at the end of 8th week. Treatment with DEHP alone resulted in a significant decrease in body and testicular weights, sperm parameters and serum hormone levels when compared with control. On the other hand, testicular antioxidant enzymes showed a significant dose-dependent increase. The expression of CYP19 mRNA was significantly reduced by increasing the doses of DEHP. Administration of celery oil along with DEHP partially prevented the decrease in body and testicular weights and enhanced epididymal sperm count, serum hormone levels and the expression of CYP19 mRNA along with diminution in the activities of SOD, GPx and CAT enzymes. The obtained results showed that the celery improved the testicular alterations induced by DEHP in albino rats.
AebiHE (1984) Catalase in vitro. Methods in Enzymology105: 121–126.
2.
AkingbemiBTGeRKlinefelterGRZirkinBRHardyMP (2004) Phthalate induced Leydig cell hyperplasia is associated with multiple endocrine disturbances. Proceedings of the National Academy of Sciences of the United States of America101: 775–780.
3.
AkingbemiBTYoukerRTSottasCMGeRKatzEKlinefelterGR. (2001) Modulation of rat Leydig cell steroidogenic function by di-(2-ethylhexyl) phthalate. Biology of Reproduction65: 1252–1259.
4.
BarlowNJFosterPM (2003): Pathogenesis of male reproductive tract lesions from gestation through adulthood following in utero exposure to di(n-butyl) phthalate. Toxicologic Pathology31: 397–410.
5.
BilinskaBGancarczykMPaziewskaACarreauS (2004) Dose and photoperiod-dependent effect of 17β-estradiol or ICI 182,780 administration on testicular structure, acceleration of spermatogenesis and aromatase immunoexpression in immature bank voles. Acta Histochemica106: 269–278.
6.
CaraniCQinKSimoniMFaustini-FustiniMSerpenteSBoydJ. (1997) Effect of testosterone and estradiol in a man with aromatase deficiency. The New England Journal of Medicine337: 91–95.
7.
CarreauSLambardSDelalandeCDenis-GaleraudIBilinskaBBourguibaS (2003) Aromatase expression and role of estrogens in male gonad: a review. Reproductive Biology and Endocrinology1: 35–40.
8.
CeccatelliSTammCZhangQChenM (2007) Mechanisms and modulation of neural cell damage induced by oxidative stress. Physiology and Behavior92: 87–92.
ChowdhuryAK (1979) Dependence of testicular germ cells on hormones: A quantitative study in hypophysectomized testosterone-treated rats. Journal of Endocrinology83: 331–340.
11.
CraigWJ (1999) Health-promoting properties of common herbs. American Journal of Clinical Nutrition70: 491–499.
12.
DavidRMMooreMRFinneyDCGuestD (2000) Chronic toxicity of di-(2-ethylhexyl) phthalate in rats. Toxicological Sciences55: 433–443.
13.
Desdoits-LethimonierCAlbertOLe BizecBPerduEZalkoDCourantF. (2012) Human testis steroidogenesis is inhibited by phthalates. Human Reproduction27(5): 1451–1459.
14.
DoullJCattleyRElcombeCLakeBGSwenbergJWilkinsonC. (1999) A cancer risk assessment of di-(2-ethylhexy1) phthalate: application of the new U.S. EPA risk assessment guidelines. Regulatory and Toxicology Pharmacology29: 327–357.
15.
DutySMSinghNPSilvaMJBarrDBBrockJWRyanL. (2003) The relationship between environmental exposures to phthalates and DNA damage in human sperm using the neutral comet assay. Environmental Health Perspectives111: 1164–1169.
16.
FisherJS (2005) Are all EDC effects mediated via steroid hormone receptors?Toxicology205: 33–41.
17.
GenisselCCarreauS (2001) Regulation of the aromatase gene expression in mature rat Leydig cells. Molecular and Cellular Endocrinology178: 141–146.
18.
GeorgeFWPetersonKG (1988) 5a-Dihydrotestosterone formation is necessary for embryogenesis of the rat prostate. Endocrinology122: 1159–1164.
19.
HalliwellBGutteridgeJMCrossCE (1992) Free radicals, antioxidants, and human disease: where are we now?Journal of Laboratory and Clinical Medicine119: 598–620.
20.
HamzaAAminA (2007) Apium graveolens modulates sodium valporate-induced reproductive toxicity in male rats. Journal of Experimental Zoology307(4): 199–206.
21.
HauserRMeekerJDDutySSilvaMJCalafatAM (2006) Altered semen quality in relation to urinary concentrations of phthalate monoester and oxidative metabolites. Epidemiology17(6): 682–691.
22.
HeckerMNewstedJMurphyMHigleyEJonesPWuRGiesyJP (2006) Human adrenocarcinoma (H295R) cells for rapid in vitro determination of effects on steroidogenesis: Hormone production. Toxicology and Applied Pharmacology217: 114–124.
23.
HessRA (2000) Oestrogen in fluid transport in efferent ducts of the male reproductive tract. Reviews of Reproduction5: 84–92.
24.
HessRA (2003) Estrogen in the adult male reproductive tract: a review. Reproductive Biology and Endocrinology1: 52–66.
25.
HowdeshellKLFurrJLambrightCRRiderCVWilsonVSGrayLE (2007) Cumulative effects of dibutyl phosphate and diethylhexyl phosphate on male rat reproductive tract: altered fetal steroid hormones and genes. Toxicological Science99: 190–202.
26.
IshigeKSchubertDSagaraY (2001) Flavonoids protect neuronal cells from oxidative stress by three distinct mechanisms. Free Radical Biology and Medicine30: 433–446.
27.
IshiharaMItohMMiyamotoKSunaSTakeuchiYTakenakaI. (2000) Spermatogenic disturbance induced by di-(2-ethylhexyl) phthalate is significantly prevented by treatment with antioxidant vitamins in the rat. International Journal of Andrology23: 85–94.
28.
ItoYYokotaHWangRYamanoshitaOIchiharaGWangH. (2005) Species differences in the metabolism of di-(2-ethylhexyl) phthalate (DEHP) in several organs of mice, rats and marmosets. Archives of Toxicology79: 147–154.
29.
KangJSMorimuraKTodaCWanibuchiHWeiMKojimaN. (2006) Testicular toxicity of DEHP, but not DEHA, is elevated under conditions of thioacetamide-induced liver damage. Reproductive Toxicology21: 253–259.
30.
KasaharaESatoEFMiyoshiMKonakaRHiramotoKSasakiJ. (2002) Role of oxidative stress in germ cell apoptosis induced by di-(2-ethylhexyl) phthalate. Biochem Journal365: 849–856.
31.
KavlockRBarrDBoekelheideKBreslinWBreyssePChapinR. (2006) NTP-CERHR Expert Panel update on the reproductive and developmental toxicity of di-(2-ethylhexyl) phthalate. Reproductive Toxicology22: 291–399.
32.
KimHSSaitoKIshizukaMKazusakaAFujitaS (2003) Short period exposure to di-(2-ethylhexyl) phthalate regulates testosterone metabolism in testis of prepubertal rats. Archvies of Toxicology77: 446–451.
33.
KochHMPreussRAngererJ (2006) Di(2-ethylhexyl) phthalate (DEHP): human metabolism and internal exposure – an update and latest results. International Journal of Andrology29: 155–165.
34.
KurahashiNKondoTOmuraMUmemuraTMaMKishiR (2005) The effects of subacute inhalation of di (2-ethylhexyl) phthalate (DEHP) on the testes of prepubertal wistar rats. Journal of Occupational Health47: 437–444.
35.
LambardSSilandreDDelalandeCDenis-GaleraudIBourguibaSCarreauS (2005) Aromatase in testis: expression and role in male reproduction. Journal of Steroid Biochemistry and Molecular Biology95: 63–69.
36.
LiLHJesterWFOrthJM (1998) Effects of relatively low levels of mono (2-ethylhexyl) phthalate on cocultured Sertoli cells and gonocytes from neonatal rats. Toxicology and Applied Pharmacology153: 258–265.
37.
LoffSKabsFWittKSartorisJMandlBNiessenKH. (2000) Polyvinylchloride infusion lines expose infants to large amounts of toxic plasticizers. Journal of Pediatric Surgery35: 1775–1781.
38.
MaffeiLMurataYRochiraVTubertGArandaCVazquezM. (2004) Dysmetabolic syndrome in a man with a novel mutation of the aromatase gene: effects of testosterone, alendronate and estradiol treatment. Journal of Clinical Endocrinology and Metabolism89: 61–70.
39.
MannT (1964) Fructose Polylos and Organic Acids. The Biochemistry of Semen and the Male Reproductive Tract. New York, NY: John Wiley, pp. 237–264.
40.
MatkovicsBKotormanMVargaISHaiDQVargaC (1998) Oxidative stress in experimental diabetes induced by streptozotocin. Acta Physiologica Hungarica85(1): 29–38.
41.
MeiselRSachsBD (1994) The physiology of male sexual behavior. In: KnobilE McNeillJD (eds) The Physiology of Reproduction. New York, NY: Raven Press, pp 3–106.
42.
MisraHPFridovichI (1972) The role of superoxide anion in the autooxidation of epinephrine and a simple assay of SOD. Journal of Biological Chemistry247: 3170–3175.
43.
MitraSKVenkatarangannaMVGopumadhavnSAnturlikarSDSeshadri UdupaUV (2001) The protective effect of HD-03 in CCL4-induced hepatic encephalopathy in rats. Phytotheraphy Research15: 493–496.
44.
MominRANairMG (2002) Antioxidant cyclooxygenase and topoisomerase inhibitory compounds from Apium graveolens seeds. Phytomedicine9(4): 312–318.
45.
NoriegaNCHowdeshellKLFurrJLambrightCRWilsonVSGrayLEJr (2009) Pubertal administration of DEHP delays puberty, suppresses testosterone production, and inhibits reproductive tract development in male Sprague-Dawley and Long-Evans rats. Toxicological Science111(1): 163–178.
46.
OishiS (1989) Effects of co-administration of di-(2-ethylhexyl) phthalate and testosterone on several parameters in the testis and pharmacokinetics of its mono-de-esterified metabolite. Archives of Toxicology63: 289–295.
47.
PakTRLynchRTsaiPS (2002) Estrogen accelerates gonadal recrudescence in photo-regressed male Siberian hamsters. Endocrinology143: 4131–4134.
48.
PantNSrivastavaSP (2003) Testicular and spermatotoxic effects of quinalphos in rats. Journal of Applied Toxicology23: 271–274.
49.
ParkJDHabeebuSSKlaassenCD (2002) Testicular toxicity of di-(2-ethylhexyl) phthalate in young Sprague Dawley rats. Toxicology171: 105–115.
50.
ParmarDSrivastavaSPSethPK (1994) Age related effects of di-(ethylhexyl) phthalate on hepatic cytochrome P450 monooxygenases in Wistar rats. Pharmacology and Toxicology75: 177–180.
51.
PentikäinenVErkkiläKSuomalainenLParvinenMDunkelL (2000) Estradiol acts as a germ cell survival factor in the human testis in vitro. Journal of clinical Endocrinology and Metabolism85: 345–350.
52.
RankJ (2005) Classification and risk assessment of chemicals: The case of DEHP in the light of reach. Journal of Transdisciplinary Environmental Studies4(3): 1–15.
53.
RegaderaJMartinez-GarciaFGonzalez-PeramatoPSerraANistalMSuarez-QuianC (2001) Androgen receptor expression in Sertoli cells as a function of seminiferous tubule maturation in the human cryptorchid testis. Journal of Clinical Endocrinology and Metabolism86: 413–421.
54.
RobertsonKMO’DonnellLJonesMEMeachemSRBoonWCFisherCR. (1999) Impairment of spermatogenesis in mice lacking a functional aromatase (cyp 19) gene. Proceedings of the National Academy of Sciences of the United States of America96: 7986–7991.
55.
RyuJYLeeBMKacewSKimHS (2007) Identification of differentially expressed genes in the testis of Sprague-Dawley rats treated with di-(n-butyl) phthalate. Toxicology234: 103–112.
56.
SandersonJTLetcherRHeneweerMGiesyJvan den BergM (2001) Effects of Chloro-s-Triazine herbicides and metabolites on aromatase activity in various cell lines and on vitellogenin production in male carp hepatocytes. Environmental Health Perspectives109: 1027–1031.
57.
ScobieGAMacphersonSMillarMRGroomeNPRomanaPGSaundersPT (2002) Human oestrogen receptors: differential expression of ER alpha and beta and the identification of ER beta variants. Steroids67: 985–992.
58.
ShalabyMAEl ZorbaHY (2010) Protective effect of celery oil, vitamin E and their combination against testicular toxicity in male rats. Global Veterinary5(2): 122–128.
59.
SharpeRM (2005) Phthalate exposure during pregnancy and lower anogenital index in boys: wider implications for the general population?Environmental Health Perspectives113: A504–A505.
60.
SharpeRMIrvineDS (2004) How strong is the evidence of a link between environmental chemicals and adverse effects on human reproductive health?Brtish Medical Journal328: 447–451.
61.
ShiZZhangHLiuYXuMDaiJ (2007) Alterations in gene expression and testosterone synthesis in the testes of male rats exposed to perfluorododecanoic acid. Toxicological Science98(1): 206–215.
62.
ShinSJeonJHParkDJangMJChoiBHJooSS. (2008) Trans-resveratrol relaxes the corpus cavernosum ex vivo and enhances testosterone levels and sperm quality in vivo. Archives of Pharmcal Research31: 83–87.
63.
SilvaMJBarrDBReidyJAMalekNAHodgeCCCaudillSP. (2004) Urinary levels of seven phthalate metabolites in the U.S. population from the National Health and Nutrition Examination Survey (NHANES) 1999–2000. Environmental Health Perspectives112: 331–338.
64.
SönmezMTurkGYuceA (2005) The effect of ascorbic acid supplementation on sperm quality, lipid peroxidation and testosterone levels of male Wistar rats. Theriogenology63: 2063–2072.
65.
SrivastavaSSrivastavaSP (1991) Effect of di-(2-ethylhexyl) phthalate on 17 beta-hydroxysteroid dehydrogenase activity in testis of rat. Toxicological Letters57(2): 235–239.
66.
SultanaSSalahuddinATamannaJSharmaS (2005) Inhibitory effect of celery seed extract on chemically induced hepatocarcinogenesis: modulation of cell proliferation, metabolism and altered hepatic foci development. Cancer Letters221: 11–20.
67.
SwanSHMainKMLiuFStewartSLKruseRLCalafatAM. (2005) Decrease in anogenital distance among male infants with prenatal phthalate exposure. Environmental Health Perspectives113: 1056–1061.
68.
TodaKOkadaTMiyauraCSaibaraT (2003) Fenofibrate, a ligand for PPAR-α, inhibits aromatase cytochrome P450 expression in the ovary of mouse. Journal of Lipid Research44: 265–270.
69.
TonkECVerhoefAGremmerERvan LoverenHPiersmaAH (2012) Relative sensitivity of developmental and immune parameters in juvenile versus adult male rats after exposure to di(2-ethylhexyl) phthalate. Toxicology and Applied Pharmacology260: 48–57.
70.
TsiDTanBK (2000) The mechanism underlying the hypocholesterolemic activity of celery extracts (aqueous and butanol extracts) in hypocholesterolemic rats. Life sciences14(66): 755–767.
71.
UzunhisarcikliMKalenderYDiricanKKalenderSOgutcuABuyukkomurcuF (2007) Acute, subacute and subchronic administration of methyl parathion-induced testicular damage in male rats and protective role of vitamins C and E. Pesticide Biochemistry and Physiology87: 115–122.
72.
VanGuilderHDVranaKEFreemanWM (2008) Twenty-five years of quantitative PCR for gene expression analysis. BioTechniques44(5): 619–626.
73.
WeiAShibamotoT (2007) Antioxidant activities and volatile constituents of various essential oils. Journal of Agricultral and Food Chemistry55: 1734–1742.
74.
WesterRCMelendresJSedikLMaibachHRiviereJE (1998) Percutaneous absorption of salicylic acid, theophylline, 2, 4-dimethylamine, diethyl hexyl phthalic acid, and ρ-aminobenzoic acid in the isolated perfused porcine skin flap compared to man in vivo. Toxicology and Applied Pharmacology151: 159–165.
75.
WilsonVSLambrightCFurrJOstbyJWoodCHeldGGrayELJr (2004) Phthalate ester-induced gubernacular lesions are associated with reduced insl3 gene expression in the fetal rat testis. Toxicology Letters146: 207–215.
76.
WyrobekAJGordonLABurkhartJGFrancisMWKappRWJrLetzG. (1983) An evaluation of the mouse sperm morphology test and other sperm tests in non-human mammals. A report of the US environmental protection agency gene-tox program. Mutation Research115(1): 1–72.
77.
YeonJEChoiKMBaikSHKimKOLimHJParkKH. (2004) Reduced expression of peroxisome proliferator-activated receptor-α may have an important role in the development of non-alcoholic fatty liver disease. Journal of Gastroenterology and Hepatology19: 799–804.
