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Basic and prophylactic study on the toxicity of endocrine disruptors and lifestyle Testicular injury by di-(2-ethylhexyl) phthalate

Research Project

Project/Area Number 11470108
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Public health/Health science
Research InstitutionKagawa Medical University

Principal Investigator

JITSUNARI fumihiko  Kagawa Medical University Professor, 医学部, 教授 (60127561)

Co-Investigator(Kenkyū-buntansha) ITOH masahiro  Tokyo Medical University, Professor, 医学部, 教授 (00232471)
ASAKAWA fumiyuki  Kurashiki University of Science and the Arts, Professor, 教養学部, 教授 (20159362)
TOKUDA masaaki  Kagawa Medical University, Professor, 医学部, 教授 (10163974)
SUNA shigeru  Kagawa Medical University, Assinstant Professor, 医学部, 助手 (40253265)
竹内 義喜  香川医科大学, 医学部, 教授 (20116619)
竹中 生昌  香川医科大学, 医学部, 教授 (40032180)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 2001: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2000: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1999: ¥2,400,000 (Direct Cost: ¥2,400,000)
KeywordsDEHP / testicular atrophy / vitamin E, C / caffeine / nicotinic acid / ethanol / oxidative stress / Ethanol / Caffeine / Nicotinic Acid / 活性酸素 / アポトーシス / エチルアルコール / カフェイン / ナイアシン / ビタミンC / ビタミンE / 初期像 / 回復 / 精巣障害 / ビタミンEC
Research Abstract

Di-(2-ethylhexyl) phthalate (DEHP) is the most common plasticizer for plastics such as polyvinyl chloride (PVC) but suspected to be an endocrine disruptor. Recent studies have shown the toxic effects of DEHP on male reproductive organs such as testicular injury in rats in both mature and growth stages, and this injury has been suggested to be due to oxidative stress induced by mono-(2-ethylhexyl) phthalate (MEHP). Since PVC containing DEHP is widely used in manufacturing consumer goods, food containers, toys, and medical instruments, DEHP contamination is widespread, and the general population is exposed to DEHP in food, water, and air, which arouses concern about human reproductive hazards.
In this study, to clarify the effects of chemical substances widely distributed in foods and beverages on the testicular toxicity of DEHP, we administered antioxidants such as vitamins E and C, caffeine, nicotinic acid, and ethanol together with DEHP to rats in the growth stage. In 4- or 5-week-old SD rats given a 1-2% DEHP containing diet for 1-2 weeks, testicular atrophy accompanied by a spermatogenesis developed. Young rats were more susceptible to the testicular toxicity of DEHP. There was a correlation between the blood or testicular MEHP concentration and the degree of DEHP-induced testicular atrophy, suggesting a dose-effect relationship between the dose of MEHP as an active toxicant and testicular injury.
In 4-week-old rats given a 2% DEHP containing diet and water supplemented with vitamins E and C, testicular atrophy was definitely inhibited. Water supplemented with caffeine (0.05w/w%), nicotinic acid (0.5 w/w%), or ethanol (2.5 or 5 v/v%) also prevented testicular atrophy in 4-week-old rats given a 1% DEHP containing diet. The action mechanism of these antioxidants was unclear. However, our results suggest the involvement of antioxidant activity and free radical scavenging capacity in the inhibition of DEHP induced testicular injury.

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (7 results)

All Other

All Publications (7 results)

  • [Publications] Ishihara M: "Spermatogenic disturbance induced by di-(2-ethylhexyl) phthalate is significantly prevented by treatment with antioxidant vitamins in the rat"International Journal of Andrology. 23. 85-94 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 須那 滋: "ラット血液、臓器中ジ(2-エチルヘキシル)フタレート(DEHP)、モノ(2-エチルヘキシル)フタレート(MEHP)の簡易分析法"産業衛生学雑誌. 43. 73-75 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ishihara, M.: "Spermatogenic disturbance induced by di-(2-ethylhexyl) phthalate is significantly prevented by treatment with antioxidant vitamins in the rat"International Journal of Andrology 2000. 23. 85-94 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Suna, S.: "Simplified determination of di-(2-ethylhexyl) phthalate (DEHP) and mono-(2-ethylhexyl) phthalate (MEHP) in blood and organs of the rat administered DEHP"Sangyo Eiseigaku Zasshi 2001. 43. 73-75 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ishihara,M.,Itoh,M.,Miyamoto,K.,Suna,S.,Takeuchi,Y.,Takenaka,I.,Jitsunari,F.: "Spermatogenic disturbance induced by di(2-ethylhexyl)phthalate is significantly prevented by treatment with antioxidant vitamines in rats."Int.J.Androl.(in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Musa,F.R.M.,Takenaka,I.,Tokuda,M.: "Effects of Luteinizing Hormone,Follicle-Stimulating Hormone,and Epidermal Growth Factor on Expression and Kinase Activity of Cyclin-Dependent Kinase 5 in Leydig TM3 and Sertoli TM4 Cell Lines."J.Andrology (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Sui,L.,Tokuda,M.,Ohno,M.,Hatase,O.,Hando,T.: "The Concurrent Expression of p27^<kip1> and Cyclin D1 in Epithelial Ovarian Tumors"Gynecol.Onol.. 73. 202-209 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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