van den Bogert C, Holtrop M, Melis T E, Roefsema P R, Kroon A M
Biochem Pharmacol. 1987 May 1;36(9):1555-9. doi: 10.1016/0006-2952(87)90126-2.
The tetracyclines inhibit specifically mitochondrial (mt) and bacterial protein synthesis when they are present in low concentrations (2-10 micrograms/ml). There is no difference between the various members of this group of antibiotics in this respect. In the present study, however, it is shown that the inhibitory effect of doxycycline on mt-protein synthesis in rat liver is partially lost after continuous treatment for more than 1 week, whereas oxytetracycline continues to inhibit mt-protein synthesis effectively after 1 week of treatment. To find an explanation for this difference between doxycycline and oxytetracycline, a detailed study was made of the distribution and the effects on mt-protein synthesis of both tetracyclines under various conditions in rat liver. The results of the studies lead to the hypothesis that doxycycline treatment induces the formation of a doxycycline complex, and thus to a reduced amount of free doxycycline. This may explain the loss of effective inhibition of mt-protein synthesis.
四环素在低浓度（2 - 10微克/毫升）时能特异性抑制线粒体（mt）和细菌的蛋白质合成。在这方面，该类抗生素的不同成员之间没有差异。然而，在本研究中发现，多西环素连续处理超过1周后，其对大鼠肝脏线粒体蛋白质合成的抑制作用部分丧失，而土霉素在处理1周后仍能有效抑制线粒体蛋白质合成。为了解释多西环素和土霉素之间的这种差异，对两种四环素在大鼠肝脏各种条件下的分布及其对线粒体蛋白质合成的影响进行了详细研究。研究结果提出了一个假设，即多西环素处理会诱导多西环素复合物的形成，从而导致游离多西环素的量减少。这可能解释了线粒体蛋白质合成有效抑制作用的丧失。
