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维甲酸的毒理学研究及其对血液和组织的影响(作者译)

[A toxicological study of etretinate and its effect on blood and tissue (author's transl)].

作者信息

Yui Y

出版信息

J Toxicol Sci. 1982 Feb;7(1):71-82. doi: 10.2131/jts.7.71.

Abstract

10 mg/kg of etretinate was administrated orally for 4 weeks to a Sprague-Dawley rat (male, approx. 140 g in weight) and its toxicity was checked at 2 and 4 weeks after the start of administration. Recovery was checked 2 and 4 weeks after end of administration. Three weeks after administration of etretinate, a decline in the increase of body weight and a decline in movement due to abnormality in the lower half of the body was seen. Two weeks after administration, the thigh bone was observed to thin and to have fragility; 4 weeks after administration the changes in the thigh bone became more eminent and the forearm was seen to thin 4 weeks after administration of etretinate, the hematological test showed an increase of leukocytes and the biochemical test showed an increase of triglycerides and phospholipids. The calcium in the thigh bone showed a notable decrease 2 and 4 weeks after administration. The decline in the increase of body weight; the increase of leukocytes, triglycerides and phospholipids; and the decrease of calcium in the thigh bone recovered to normal 2 weeks after the end of administration. Blood retinol decreased and a decrease in retinyl palmitate and retinol in the liver was induced by the administration of etretinate. The toxicity of etretinate was seen to be comparatively lower than that of retinoid. A more detailed study is thought to be needed concerning the changes in bone.

摘要

将10毫克/千克的依曲替酯口服给予一只体重约140克的雄性斯普拉格-道利大鼠,持续4周,并在给药开始后的第2周和第4周检查其毒性。在给药结束后的第2周和第4周检查恢复情况。给予依曲替酯3周后,观察到体重增加下降,且由于身体下半部异常导致活动减少。给药2周后,观察到大腿骨变细且易碎;给药4周后,大腿骨的变化更加明显,给药4周后还观察到前臂变细。给予依曲替酯后,血液学检查显示白细胞增加,生化检查显示甘油三酯和磷脂增加。给药后第2周和第4周,大腿骨中的钙显著下降。体重增加下降、白细胞、甘油三酯和磷脂增加以及大腿骨中钙减少在给药结束后2周恢复正常。血液视黄醇减少,给予依曲替酯可导致肝脏中棕榈酸视黄酯和视黄醇减少。依曲替酯的毒性相对低于类维生素A。关于骨骼变化,认为需要进行更详细的研究。

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