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題 名 | Pyrimethamine對大鼠之急性中毒及併用磺胺藥、葉酸或亞葉酸對胎兒之影響 |
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作 者 | 郭宗甫; 劉朝鑫; | 書刊名 | 臺灣畜牧獸醫學會會報 |
卷 期 | 65:1 1995.03[民84.03] |
頁 次 | 頁35-45 |
分類號 | 437.23 |
關鍵詞 | 大鼠; 磺胺藥; 葉酸; 亞葉酸; 胚胎毒性; Rat; Pyrimethamine; Sulfadimethoxine folic acid; Fonilic acid; Embryo toxicity; |
語 文 | 中文(Chinese) |
中文摘要 | Pyrimethemine(PY)對雌大白鼠口服一次之百分之五十致死劑量是373.33mgPY╱kgB.W.,求得PY對孕鼠之安全域為171.25,其安全指數為0.0058。受PY急性中毒死亡之雌鼠,有心肌透明樣壞死、肌細胞橫紋消失;腎小管上皮給胞局部性核濃縮、細胞質瀰散之壞死現象,其他器官正常。並得知二氫葉酸還原?(DHFR)活性受葉酸拮抗劑PY抑制達3至4時,即有可能造成死亡。至於PY併用磺胺藥Sulfadimethoxine(SDM)方面,無論是併用10mg SDM╱B.W.或20mgSDM╱kg B.W.,在給與較低劑量2mgPY╱B.W.時,只有對胎重有顯著性減少差異,給與較高劑量4mgPY╱kg B.W.時則顯示不出有任何加重致畸形性的影響。給與4mgPY╱kg B.W.及葉酸(FA) 2mgFA╱kg B.W.(含)以上時,反而對死亡和被吸收胚胎數目有極顯著增加,顯然併用葉酸有不利的影響。給與4mgPY╱ kg B.W.亞葉酸(FNA) 0.5mg FAN╱ kg B.W.(含)以上時,對死亡和被吸收胚胎數目有極顯著減少,顯然併用亞葉酸對PY致鼠胚胎之致畸形性有改善效果。 |
英文摘要 | The LD50 of pyrimethamine (PY) for adult female rat at single dose was found to be 373.33 mg╱kg. The safety margin of PY and safety index for pregnant rat were 171.25 and 0.0058 respectively. Female rats that died due to acute PY poisoning showed the following pathological changes: hyalinized necrosis of myocardium, loss of striation of cardiac muscular cells, local nuclear pyknosis, and cytoplasmic diffusion type necrosis of renal tubule epithelial cell, but the rest of the visceral organs were normal. Since PY could inhibit the activity of Dihydrofolate reductace (DHFR) as folic acid antagonist and if the degree of nihibition increased 3 or 4times, this could lead to the death of rats. On the other hand, no enhancemant of teratogenicity was observed when 4 mg╱kg PY with 10 or 20 mg╱kg sulfadimethoxine (SDM) was given to the rats. However the fetal body weight was significantly reduced when 2 mg ╱kg PY was given together with 10or 20 mg ╱kg SDM (P<0.05). When 4mg╱kg PY with 2mg╱kg folic acid (FA) or above were given, the number of dead and resorptive fetus unexpectedly increased significantly (P<0.05). Evidently, the combination of PY and folic acid had adverse effect to the fetus. When 4mg╱kg PY with 0.5 mg╱kg folinic acid (FNA) or above were giren, the number of dead and resorptive fetus were significantly reduced (P<0.05). Thus, a combination of PY and FNA N.Should be administered together to reduce the degree of teratogenicity. |
本系統中英文摘要資訊取自各篇刊載內容。