四环素叉向异构体及其脱水物的毒性探讨

本文比较了四环素,脱水四环素,叉向四环素及脫水叉向四环素的毒性。急性毒性以叉向四环素为最大,小白鼠靜脉LD₅₀为85.8毫克/公斤,而四环素,脫水四环素及脫水叉向四环素的LD₅₀分別为160.7毫克/公斤,134.2毫克/公斤及193毫克/公斤。亚急性毒性则以脫水叉向四环素为最大,小白鼠不论靜脉注射1毫克/0.5毫升或口服12毫克/0.2毫升,均能出现较重的糖尿及蛋白尿,肾曲管发生较重的病变,可能是临床引起Fanconi症候羣的主要物质。

A Study of the Toxicity of the Epimeric Pairs of Tetracycline

Problems concerning the toxicity of tetracycline, 4-epitetracycline, anhydrotetracycline and anhydro-4-epi-tetracycline are discussed in this paper. Among the above preparations, the 4-epi-tetracycline is most toxic to mice. When given intravenously its LD₅₀ to mice is 85.8 mg/kg, as compared with 160.7 mg/kg of tetracycline, 134.2 mg/kg of anhydrotetracycline and 193 mg/kg of anhydro-4-epi-tetracycline. In sub-acute toxicity study anhydro-4-epi-tetracycline exhibited most toxic effects in mice. When given intravenously 1 mg/day, or even 12 mg/day orally, severe diabetic urine and proteinuria were observed, and serious pathologic change of the convoluted tube appeared. Our experiment indicates that anhydro-4-epi-tetracycline may be the chief material responsible for Fanconi syndrome.