Aktan Bülent, Taysi Seyithan, Gümüştekin Kenan, Uçüncü Harun, Memişoğullari Ramazan, Save Kürşad, Bakan Nuri
Department of Otorhinolaryngology-Head and Neck Surgery, Atatü University, Medical School, Erzurum, Turkey.
Pol J Pharmacol. 2003 Nov-Dec;55(6):1105-10.
Although the long-term administrations of macrolide antibiotics are effective for diffuse panbronchiolitis, otitis media with effusion (OME), and some other diseases, their mechanism of action has not been fully understood. In order to elucidate the mechanisms of possible effects of macrolide antibiotics on activities of erythrocyte nitric oxide synthase (NOS), xanthine oxidase (XO), and malondialdehyde (MDA) levels in experimental OME, we aimed to evaluate the effect of macrolide antibiotics (erythromycin, azithromycin, roxithromycin, and clarithromycin) using an experimental guinea pig otitis media model. Erythrocyte NOS, XO activities, and MDA level were measured in all groups. Erythrocyte NOS activities were significantly higher in erythromycin-, azithromycin-, roxithromycin-, and clarithromycin-treated groups than in the experimental group. Erythrocyte XO activities were significantly lower in erythromycin-, azithromycin-, roxithromycin-, and clarithromycin-treated groups than in the control group. However, erythrocyte XO activities in experimental group were significantly higher than those of control group. Erythrocyte MDA levels were significantly lower in erythromycin-, azithromycin-, roxithromycin-, and clarithromycin-treated groups than those of the experimental group. The MDA levels in erythromycin- and roxithromycin-treated groups were significantly higher than those of azithromycin-treated group. The MDA levels in azithromycin-treated group were significantly lower than those of roxithromycin-treated group. In conclusion, the present study shows that the macrolide antibiotics (erythromycin, azithromycin, roxithromycin, and clarithromycin) increase NOS activity, decrease XO activity and MDA level, which is an important indicator of oxidative stress.
尽管大环内酯类抗生素的长期给药对弥漫性泛细支气管炎、渗出性中耳炎（OME）及其他一些疾病有效，但其作用机制尚未完全明确。为了阐明大环内酯类抗生素对实验性OME中红细胞一氧化氮合酶（NOS）活性、黄嘌呤氧化酶（XO）及丙二醛（MDA）水平可能产生影响的机制，我们旨在利用实验性豚鼠中耳炎模型评估大环内酯类抗生素（红霉素、阿奇霉素、罗红霉素和克拉霉素）的作用效果。对所有组的红细胞NOS、XO活性及MDA水平进行了测定。红霉素、阿奇霉素、罗红霉素和克拉霉素治疗组的红细胞NOS活性显著高于实验组。红霉素、阿奇霉素、罗红霉素和克拉霉素治疗组的红细胞XO活性显著低于对照组。然而，实验组的红细胞XO活性显著高于对照组。红霉素、阿奇霉素、罗红霉素和克拉霉素治疗组的红细胞MDA水平显著低于实验组。红霉素和罗红霉素治疗组的MDA水平显著高于阿奇霉素治疗组。阿奇霉素治疗组的MDA水平显著低于罗红霉素治疗组。总之，本研究表明大环内酯类抗生素（红霉素、阿奇霉素、罗红霉素和克拉霉素）可增加NOS活性，降低XO活性及MDA水平，MDA水平是氧化应激的重要指标。
