著者

Kuninori Iwayama Yusuke Takashima Ko-ichi Ohtaki Kikutaro Endoh Yoshiko Tampo Nobumasa Hayase

出版者

Japanese Society of Pharmaceutical Health Care and Sciences

雑誌

医療薬学 (ISSN:1346342X)

巻号頁・発行日

vol.38, no.10, pp.617-627, 2012-10-10 (Released:2013-10-10)

参考文献数

37

被引用文献数

1 1

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We examined the effects of 8 macrolide antimicrobial agents, including 14-, 15- and 16-membered ring lactone and ketoride derivatives, on hemolysis induced by lysophosphatidylcholine (LPC) in human erythrocytes. LPC induced hemolysis at concentrations above the critical micelle concentration (4 µM). Vitamin E (α-tocopherol), used as a reference drug, attenuated the 50% hemolysis induced by 6 µM LPC when present at concentrations between 1 µM and 100 mM. Clarithromycin significantly attenuated LPC-induced hemolysis at a wider range of concentrations (100 nM to 1 mM), but other macrolides attenuated hemolysis only at high concentrations (100 µM and/or 1 mM). Since vitamin E tends to stabilize membranes due to its high lipophilicity, it appears that the high lipophilicity of clarithromycin is responsible for its protective action against damage induced by LPC. However, rokitamycin was not effective, although it is more lipophilic than clarithromycin, indicating that factors other than high lipophilicity are responsible for the protective effects of macrolide antimicrobial agents against LPC-induced hemolysis. Neither vitamin E nor clarithromycin attenuated hypotonic hemolysis (60 mM NaCl) at concentrations that inhibit LPC-induced hemolysis. On the other hand, both vitamin E and clarithromycin affected LPC micelle formation, suggesting that these drugs directly bind to LPC. We therefore believe that the protective effects of clarithromycin on LPC-induced hemolysis may be related physicochemically to its high lipophilicity and 14-membered ring lactone structure, which help maintain erythrocyte membrane integrity by preventing LPC micelle formation. These drugs likely do not act by a mechanism that protects against osmotic imbalance.