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Endosulfan, cypermethrin, 2,4-D ve trifluralin’in androjenik ve anti-androjenik etkilerinin hershberger metoduyla araştırılması

Yıl 2021, , 109 - 116, 25.06.2021
https://doi.org/10.33716/bmedj.954025

Öz

Amaç: Bu çalışma; organoklorlu (Endosulfan) ve pyrethroid (Cypermethrin) pestisitler ile herbisitlerin (2,4-D ve Trifluralin) Hershberger metodu ile peri-pubertal erkek sıçan modelinde serum LH ve FSH düzeyleri ile androjen duyarlı dokular üzerine androjenik ve anti-androjenik etkilerini araştırmak amacıyla planlandı.Gereç ve Yöntem: Çalışmada 56 adet peri-pubertal 42 günlük erkek Sprague Dawley sıçan kullanıldı.İlk grup sham kastrasyon olarak ayrıldı. Geriye kalan 49 adet sıçan kastre edildi. On günlük iyileşme süresinin sonunda sıçanlar yedi gruba daha ayrıldı: Kastrasyon grubu; Testosteron propiyonat (TP) grubu; TP+Flutamide grubu; TP+Endosulfan grubu; TP+2,4-D grubu; TP+Cypermethrin grubu; TP+Trifluralin grubu. Son uygulamadan 24 saat sonra sıçanlar dekapite edilerek kan örnekleri toplandı. Tüm hayvanların prostat bezi, bulbouretral bezleri, seminal vezikülleri ve musculus levator ani (mLA) diseke edilerek tartıldı. Serum LH, FSH ve testosteron düzeyleri ELISA yöntemi ile belirlendi.Bulgular: Kastrasyon, tüm androjen-duyarlı doku ağırlıklarında azalmaya neden olurken (p<0.001); kastre edilen hayvanlara TP uygulanması bu dokuların ağırlıklarının sham grubu değerlerine dönmesini sağladı (p<0.001). Endosulfan, Cypermethrin ve Trifluralin bulbouretral bez ağırlıklarında TP grubuna göre anlamlı azalmaya yol açarken (p<0.01); 2,4-D ise vesicula seminalis ağırlıklarında anlamlı artış oluşturdu (p<0.01). Uygulanan test bileşiklerinden hiçbiri prostat ve mLA ağırlıklarında TP grubuna göre anlamlı fark oluşturmadı (p>0.05). 2,4-D, Cypermethrin ve Trifluralin serum FSH düzeylerinde anlamlı artışa yol açarken; serum LH düzeylerindeki artış sadece Trifluralin grubunda istatistiksel olarak anlamlı idi. Sonuç: Çalışmadan elde edilen bulgular, Hershberger metodunda Endosulfan, Cypermethrin ve Trifluralin’in bulbouretral bez üzerinde anti-androjenik; 2,4-D’nin ise vesicula seminalis üzerinde androjenik etkilere sahip olduğunu göstermiştir. Bu çevresel kirleticilerin erkek üreme fonksiyonlarını olumsuz yönde etkileyebileceği öngörülebilir. 

Destekleyen Kurum

Fırat Üniversitesi Bilimsel Arastırma Projelendirme (FÜBAP)

Proje Numarası

1347

Kaynakça

  • Safe S. Environmental estrogens: roles in male reproductive tract problems and in breast cancer. Reviews on Environmental Health, 2002; 17: 253-262.
  • European Commission, Weybridge Workshop (1996). European workshop on the impact of endocrine disruptors on human health and wildlife. Report of proceedings, 2-4 December 1996, Weybridge, UK.
  • Gray LE, Wilson V, Noriega N, Lambright C, Furr J, Stoker TE, et al. Use of the laboratory rat as a model in endocrine disruptor screening and testing. ILAR Journal, 2004; 45: 425-437.
  • Massaad C, Entezami F, Massade L, Benahmed M, Olivennes F, Barouki R, et al. How can chemical compounds alter human fertility? Eur J Obstet Gynecol Reprod Biol, 2002; 100: 127-137.
  • Waring RH, Harris RM. Endocrine disrupters: a human risk? Molecular and Cellular Endocrinology, 2005; 244: 2-9.
  • Sun H, Xu XL, Xu LC, Song L, Hong X, Chen JF, et al. Antiandrogenic activity of pyrethroid pesticides and their metabolite in reporter gene assay. Chemosphere, 2007; 66: 474-479.
  • Vallack HW, Bakker DJ, Brandt I, Broström-Lunden E, Brouwer A, Bull KR, et al. Controlling persistent organic pollutantswhat’s next? Environmental Toxicology and Pharmacology, 1998; 6: 143-175.
  • Yalvaç M. Göksu deltası sucul ekosisteminde endosülfan ve methamidophos pestisitlerinin kalıntı düzeylerinin araştırılması.Mersin Üniversitesi, Çevre Mühendisliği AD, 2005.
  • ATSDR.(1995).Endosulfan data sheet Agency for Toxic Substances and Diseases Registry,public health services US department of health and human services, US Sep 95, 3p.
  • Farag AT, Goda NF, Shaaban NA, Mansee AH. Effects of oral exposure of synthetic pyrethroid, cypermethrin on the behavior of F1-progeny in mice. Reproductive Toxicology, 2007; 23: 560-567.
  • McCarthy AR, Thomson BM, Shaw IC, Abell AD. Estrogenicity of pyrethroid insecticide metabolites. Journal of Environmental Monitoring, 2006; 8: 197-202.
  • Elbetieha A, Da’as SI, Khamas W, Darmani H. Evaluation of the toxic potentials of cypermethrin pesticide on some reproductive and fertility parameters in the male rats. Arch Environ Contam Toxicol, 2001; 41: 522-528.
  • Kim HJ, Park YI, Dong MS. Effects of 2,4-D and DCP on the DHT-induced androgenic action in human prostate cancer cells. Toxicological Sciences, 2005; 88: 52-59.
  • Oakes DJ, WebsterWS, Brown-Woodman PDC, Ritchie HE. Testicular changes induced by chronic exposure to the herbicide formulation, Tordon 75D (2,4 dichlorophenoxyacetic acid and picloram) in rats. Reproductive Toxicology, 2002; 16: 281-289.
  • Lerda D, Rizzi R. Study of reproductive function in persons occupationally exposed to 2,4-dichlorophenoxyacetic acid (2,4-D). Mutation Research, 1991; 262: 47-50.
  • Kamburoğlu Çebi Ü, Çakır R, Tok HH. Tarla koşullarında uygulanan trifluralin herbisidinin toprakta taşınımı ve birikimi. Toprak Bilimi ve Bitki Besleme Dergisi, 2019; 7(1): 1-9.
  • Kennel PF, Pallen CT, Bars GR. Evaluation of the rodent Hershberger assay using three reference endocrine disrupters (androgen and antiandrogens). Reproductive Toxicology, 2004; 18: 63-73.
  • Toppari J, Haavisto AM, Alanen M. Changes in male reproductive health and effects of endocrine disrupters in Scandinavian countries. Cad Saude Publica, 2002; 18: 413-420.
  • Stoker TE, Parks LG, Gray LE, Cooper RL. Endocrine-disrupting chemicals: prepubertal exposures and effects on sexual maturation and thyroid function in the male rat. A focus on the EDSTAC recommendations. Endocrine Disrupter Screening and Testing Advisory Committee. Critical Reviews in Toxicology, 2000; 30: 197-252.
  • Kurt PB and Ozkoc HB. A survey to determine levels of chlorinated pesticides and PCBs in mussels and seawater from the Mid-Black Sea Coast of Turkey. Marine Pollution Bulletin, 2004; 48: 1076-1083.
  • Çok İ, Donmez MK and Karakaya AE. Levels and trends of chlorinated pesticides in human breast milk from Ankara residents: comparison of concentrations in 1984 and 2002. Bull Environ Contam Toxicol, 2004; 72: 522-529.
  • Ashby J, Lefevre PA. Preliminary evaluation of the major protocol variables fort he Hershberger castrated male rat assay for the detection of androgens, antiandrogens and metabolic modulators. Regulatory Toxicology and Pharmacology, 2000; 31: 92-105.
  • Singh SK, Pandey RS. (1990). Effect of sub-chronic endosulfan exposures on plasma gonadotrophins, testosterone, testicular testosterone and enzymes of androgen biosynthesis in rat. Indian Journal of Experimental Biology, 1990; 28: 953-956.
  • Jaiswal A, Parihar VK, Kumar MS, Manjula SD, Krishnanand BR, Shanbhag R, Unnikrishnan MK. 5-aminosalicylic acid reverses endosulfan-induced testicular toxicity in male rats. Mutation Research, 2005; 585: 50-59.
  • Chitra KC, Latchoumycandane C, Mathur PP. Chronic effect of endosulfan on the testicular function of rat. Asian Journal of Andrology, 1999; 1: 203-206.
  • Charles JM. Hanley TR Jr, Wilson RD, van Ravenzwaay B, Bus JS. Developmental toxicity studies in rats and rabbits on 2,4-dichlorophenoxyacetic acid and its forms. Toxicological Sciences, 2001; 60: 121-131.
  • Kim HJ, Kim WD, Kwon TH, Kim DH, Park YI, Dong MS. Mechanism of phenoxy compounds as an endocrine disruptor. J Toxicol Pub Health, 2002; 18: 331-339.
  • Garry VF, Tarone RE, Kirsch IR, Abdallah JM, Lombardi DP, Long LK, et al. Biomarker correlations of urinary 2,4-D levels in foresters: genomic instability and endocrine disruption. Environ Health Perspect, 2001; 109: 495-500.
  • Xue N, Xu X, Jin Z. Screening 31 endocrine-disrupting pesticides in water and surface sediment samples from Beijing Guanting reservoir. Chemosphere, 2005; 61: 1594-1606.
  • Shariati M, Noorafshan A, Mokhtari M, Askari HR. The effects of trifluralin on LH, FSH and testosterone hormone levels and testis histological changes in adult rats. International Journal of Fertility & Sterility, 2008; 2(1): 23-28.

Investigation of the androgenic and anti-androgenic effects of endosulfan, cypermethrin, 2,4-D and trifluralin by hershberger assay

Yıl 2021, , 109 - 116, 25.06.2021
https://doi.org/10.33716/bmedj.954025

Öz

Aim: This study was aimed to investigate the androgenic and anti-androgenic effects of organochlorid (Endosulfan) and pyrethroid (Cypermethrin) pesticides and herbicides (2,4-D and Trifluralin), on serum LH and FSH levels and androgen-sensitive tissues in peri-pubertal rat model with Hershberger assay. Material and Method: 56 peri-pubertal 42 days old Sprague Dawley rats were used in the study. The first group was separated as sham castration. The remaining 49 rats were castrated. After 10 days recovery period, rats were divided into further seven groups: Castration group; Testosterone Propionate (TP) group; TP+Flutamide group; TP+Endosulfan group; TP+2,4-D group; TP+Cypermethrin group; TP+Trifluralin group. 24 hours after the last application, rats were decapitated and blood samples were obtained. Prostate, bulbourethral gland, vesicula seminalis and musculus levator ani (mLA) were dissected and weighed. Serum LH, FSH and testosteron levels were determined with ELISA. Result: Castration caused significant reduction in all androgen-sensitive tissue weights n(p<0.001); whereas TP application to the castrated animals recovered this tissue weights to sham group levels (p<0.001). While Endosulfan, Cypermethrin and Trifluralin caused significant decrease in bulbourethral gland weights (p<0.01); 2,4-D significantly increased vesicula seminalis weights compared to TP group (p<0.01). None of the applied test compounds caused significant differences in prostate and mLA weights compared to TP group (p>0.05). 2,4-D, Cypermethrin and Trifluralin significantly increased serum FSH levels; but the increase in serum LH levels was only significant in Trifluralin group. Conclusion: Data obtained from this study showed that 2,4-D has androjenic effects on vesicula seminalis whereas Endosulfan, Cypermethrin and Trifluralin have anti-androgenic effects on bulbourethral gland. It can be suggested that, these environmental pollutants could affect male reproductive functions negatively. 

Proje Numarası

1347

Kaynakça

  • Safe S. Environmental estrogens: roles in male reproductive tract problems and in breast cancer. Reviews on Environmental Health, 2002; 17: 253-262.
  • European Commission, Weybridge Workshop (1996). European workshop on the impact of endocrine disruptors on human health and wildlife. Report of proceedings, 2-4 December 1996, Weybridge, UK.
  • Gray LE, Wilson V, Noriega N, Lambright C, Furr J, Stoker TE, et al. Use of the laboratory rat as a model in endocrine disruptor screening and testing. ILAR Journal, 2004; 45: 425-437.
  • Massaad C, Entezami F, Massade L, Benahmed M, Olivennes F, Barouki R, et al. How can chemical compounds alter human fertility? Eur J Obstet Gynecol Reprod Biol, 2002; 100: 127-137.
  • Waring RH, Harris RM. Endocrine disrupters: a human risk? Molecular and Cellular Endocrinology, 2005; 244: 2-9.
  • Sun H, Xu XL, Xu LC, Song L, Hong X, Chen JF, et al. Antiandrogenic activity of pyrethroid pesticides and their metabolite in reporter gene assay. Chemosphere, 2007; 66: 474-479.
  • Vallack HW, Bakker DJ, Brandt I, Broström-Lunden E, Brouwer A, Bull KR, et al. Controlling persistent organic pollutantswhat’s next? Environmental Toxicology and Pharmacology, 1998; 6: 143-175.
  • Yalvaç M. Göksu deltası sucul ekosisteminde endosülfan ve methamidophos pestisitlerinin kalıntı düzeylerinin araştırılması.Mersin Üniversitesi, Çevre Mühendisliği AD, 2005.
  • ATSDR.(1995).Endosulfan data sheet Agency for Toxic Substances and Diseases Registry,public health services US department of health and human services, US Sep 95, 3p.
  • Farag AT, Goda NF, Shaaban NA, Mansee AH. Effects of oral exposure of synthetic pyrethroid, cypermethrin on the behavior of F1-progeny in mice. Reproductive Toxicology, 2007; 23: 560-567.
  • McCarthy AR, Thomson BM, Shaw IC, Abell AD. Estrogenicity of pyrethroid insecticide metabolites. Journal of Environmental Monitoring, 2006; 8: 197-202.
  • Elbetieha A, Da’as SI, Khamas W, Darmani H. Evaluation of the toxic potentials of cypermethrin pesticide on some reproductive and fertility parameters in the male rats. Arch Environ Contam Toxicol, 2001; 41: 522-528.
  • Kim HJ, Park YI, Dong MS. Effects of 2,4-D and DCP on the DHT-induced androgenic action in human prostate cancer cells. Toxicological Sciences, 2005; 88: 52-59.
  • Oakes DJ, WebsterWS, Brown-Woodman PDC, Ritchie HE. Testicular changes induced by chronic exposure to the herbicide formulation, Tordon 75D (2,4 dichlorophenoxyacetic acid and picloram) in rats. Reproductive Toxicology, 2002; 16: 281-289.
  • Lerda D, Rizzi R. Study of reproductive function in persons occupationally exposed to 2,4-dichlorophenoxyacetic acid (2,4-D). Mutation Research, 1991; 262: 47-50.
  • Kamburoğlu Çebi Ü, Çakır R, Tok HH. Tarla koşullarında uygulanan trifluralin herbisidinin toprakta taşınımı ve birikimi. Toprak Bilimi ve Bitki Besleme Dergisi, 2019; 7(1): 1-9.
  • Kennel PF, Pallen CT, Bars GR. Evaluation of the rodent Hershberger assay using three reference endocrine disrupters (androgen and antiandrogens). Reproductive Toxicology, 2004; 18: 63-73.
  • Toppari J, Haavisto AM, Alanen M. Changes in male reproductive health and effects of endocrine disrupters in Scandinavian countries. Cad Saude Publica, 2002; 18: 413-420.
  • Stoker TE, Parks LG, Gray LE, Cooper RL. Endocrine-disrupting chemicals: prepubertal exposures and effects on sexual maturation and thyroid function in the male rat. A focus on the EDSTAC recommendations. Endocrine Disrupter Screening and Testing Advisory Committee. Critical Reviews in Toxicology, 2000; 30: 197-252.
  • Kurt PB and Ozkoc HB. A survey to determine levels of chlorinated pesticides and PCBs in mussels and seawater from the Mid-Black Sea Coast of Turkey. Marine Pollution Bulletin, 2004; 48: 1076-1083.
  • Çok İ, Donmez MK and Karakaya AE. Levels and trends of chlorinated pesticides in human breast milk from Ankara residents: comparison of concentrations in 1984 and 2002. Bull Environ Contam Toxicol, 2004; 72: 522-529.
  • Ashby J, Lefevre PA. Preliminary evaluation of the major protocol variables fort he Hershberger castrated male rat assay for the detection of androgens, antiandrogens and metabolic modulators. Regulatory Toxicology and Pharmacology, 2000; 31: 92-105.
  • Singh SK, Pandey RS. (1990). Effect of sub-chronic endosulfan exposures on plasma gonadotrophins, testosterone, testicular testosterone and enzymes of androgen biosynthesis in rat. Indian Journal of Experimental Biology, 1990; 28: 953-956.
  • Jaiswal A, Parihar VK, Kumar MS, Manjula SD, Krishnanand BR, Shanbhag R, Unnikrishnan MK. 5-aminosalicylic acid reverses endosulfan-induced testicular toxicity in male rats. Mutation Research, 2005; 585: 50-59.
  • Chitra KC, Latchoumycandane C, Mathur PP. Chronic effect of endosulfan on the testicular function of rat. Asian Journal of Andrology, 1999; 1: 203-206.
  • Charles JM. Hanley TR Jr, Wilson RD, van Ravenzwaay B, Bus JS. Developmental toxicity studies in rats and rabbits on 2,4-dichlorophenoxyacetic acid and its forms. Toxicological Sciences, 2001; 60: 121-131.
  • Kim HJ, Kim WD, Kwon TH, Kim DH, Park YI, Dong MS. Mechanism of phenoxy compounds as an endocrine disruptor. J Toxicol Pub Health, 2002; 18: 331-339.
  • Garry VF, Tarone RE, Kirsch IR, Abdallah JM, Lombardi DP, Long LK, et al. Biomarker correlations of urinary 2,4-D levels in foresters: genomic instability and endocrine disruption. Environ Health Perspect, 2001; 109: 495-500.
  • Xue N, Xu X, Jin Z. Screening 31 endocrine-disrupting pesticides in water and surface sediment samples from Beijing Guanting reservoir. Chemosphere, 2005; 61: 1594-1606.
  • Shariati M, Noorafshan A, Mokhtari M, Askari HR. The effects of trifluralin on LH, FSH and testosterone hormone levels and testis histological changes in adult rats. International Journal of Fertility & Sterility, 2008; 2(1): 23-28.
Toplam 30 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Klinik Tıp Bilimleri
Bölüm ARAŞTIRMA MAKALESİ
Yazarlar

Özgür Bulmuş 0000-0001-7736-402X

Süleyman Sandal 0000-0002-8916-3329

Zafer Şahin 0000-0001-7982-7155

Sedat Yıldız 0000-0002-7872-790X

Bayram Yılmaz 0000-0002-2674-6535

Proje Numarası 1347
Yayımlanma Tarihi 25 Haziran 2021
Yayımlandığı Sayı Yıl 2021

Kaynak Göster

APA Bulmuş, Ö., Sandal, S., Şahin, Z., Yıldız, S., vd. (2021). Endosulfan, cypermethrin, 2,4-D ve trifluralin’in androjenik ve anti-androjenik etkilerinin hershberger metoduyla araştırılması. Balıkesir Medical Journal, 5(2), 109-116. https://doi.org/10.33716/bmedj.954025