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題 名 | Antagonistic and Synergistic Effects of Carbendazim and Flutamide Exposures in Utero on Reproductive and Developmental Toxicity in Rats=懷孕期間暴露貝芬替與Flutamide對大鼠仔代生殖與發育毒性之拮抗與協同作用影響 |
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作 者 | 呂水淵; 廖俊旺; 郭明良; 黃振聲; 翁祖輝; | 書刊名 | 藥物食品分析 |
卷 期 | 14:2 2006.06[民95.06] |
頁 次 | 頁120-132+219 |
分類號 | 437.23 |
關鍵詞 | 貝芬替; 免賴得; 生殖發育; 子宮暴露; Carbendazim; Benomyl; Flutamide; Reproductive development; In utero; |
語 文 | 英文(English) |
中文摘要 | 貝芬替 (carbendazim) 與其前驅物免賴得 (benomyl) 為全身性殺菌劑農藥,它們對雄大鼠均具有生殖與發育毒性。本研究主要目的為探討大鼠懷孕期間暴露貝芬替改變仔代雄性素依存性的發育指標能力,並探討雄性素拮抗劑flutamide對貝芬替請發大鼠生殖與發育毒性之影響。雌大鼠於懷孕第0至20天時,每天一次口服投予6.25、12.5及25mg/kg貝芬替,25、50及100mg/kg免賴得,0.6、2.5及10mg/kg flutamide;另有一批雌大鼠於相同懷孕期間每天一次,共同口服投予25mg/kg貝芬替或100mg/kg免賴得與0.6、2.5及10mg/kg flutamide。各種不同處理組均降低仔代大鼠出生後第l與第21天存活率。對仔代雄大鼠而言,處理12.5與25mg/kg貝芬替可請發出生後第2天雄性素作用指標肛門-陰莖距的增長。投予免賴得,同樣可增加仔代雄大鼠肛門-陰莖距。當共同給予25mg/kg貝芬替與0.6、2.5及10mg/kg flutamide時可阻斷貝芬替所增加之肛門-陰莖距。貝芬替典免賴得對仔代雄大鼠誘增之肛門-陰莖距,在仔代出生後第22天及其後即漸漸回復正常。貝芬替對出生後56天仔代雄大鼠其他與雄性素有關之指標如畢丸與副畢丸異常、陰莖尿道下裂、腹部乳頭滯留、前列腺、貯精囊、球海棉體肌與提睪肌等組織重量均無明顯作用;令人驚訝的是,貝芬替可桔抗flutamide對上述與雄性素有關指標的作用。對仔代雌大鼠而言,在出生後56天貝芬替可對flutamide所誘發之肝與腎重增加,產生協同作用。貝芬替對仔代雌大鼠生殖器官無明顯作用。這些結果顯示,懷孕期間暴露於貝芬替對仔代雄大鼠誘發暫時性且微弱的雄性韋激性作用,並減少flutamide對雄大鼠之抗雄性激素作用;另外,貝芬替對仔代雌大鼠會促進flutamide所誘發之肝與腎重增加。懷孕期間,貝芬替與flutamide拮抗或協同交互作用,有待進一步研究。 |
英文摘要 | Carbendazim (methyl 2-benzimidazolecarbamate) and its parent compound benomyl are systemic fungicides that have reproductive and developmental toxicity in male rats. The major objectives of this study were to determine the ability of carbendazim exposure in utero to alter androgen-dependent development markers in rat offspring and investigate the effects of antiandrogen flutamide on the carbendazim-mediated reproductive and developmental alterations. Pregnant female rats were treated with 6.25, 12.5 or 25 mg/kg carbendazim, 25, 50 or 100 mg/kg benomyl, and 0.6, 2.5 or 10 mg/kg flutamide by gavage once daily from gestational day 0 to 20. Alternatively, another group of female rats was cotreated with 25 mg/kg carbendazim or 100 mg/kg benomyl and 0.6, 2.5, and 10 mg/kg flutamide. The various treatments decreased the survival rates of pups on postnatal day (PND) 1 and 21. In male offspring, 12.5 and 25 mg/kg carbendazim increased anogenital distance (AGD), an androgen-dependent marker, on PND 2. Treatment with benomyl also increased AGD. Cotreatment with 25 mg/kg carbendazim with 0.6, 2.5, and 10 mg/kg flutamide blocked the androgenic effect on AGD induced by carbendazim. The androgenic effects of carbendazim and benomyl on AGD were reversible on PND 22 and later. Carbendazim had no effects on other androgen-dependent markers including testis and epididymis malformations, hypospadias, nipple retention, and organ weights of seminal vesicle and levator ani bulbocavernosus muscle on PND 56. Surprisingly, carbendazim antagonized the antiandrogenic effects on these markers induced by flutamide cotreatment. In female offspring, carbendazim produced synergistic effects on the flutamide cotreatment-mediated increases of organs weights in liver and kidney on PND 56. Carbenazim had no marked effects on female reproductive organs. These findings show that carbendazim exposure in utero displays a transient and weak androgenic effect and reduces flutamide antiandrogenicity in male rats. The fungicide enhances flutamide-mediated liver and kidney weight increases in female rats. The antagonistic and synergistic carbendazim and flutamide interactions in utero warrant further investigations. |
本系統中英文摘要資訊取自各篇刊載內容。