Characterization of the antinociceptive and anti-inflammatory activities of doxycycline and minocycline in different experimental models
Characterization of the antinociceptive and anti-inflammatory activities of doxycycline and minocycline in different experimental models
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DOI：
10.1016/j.ejphar.2007.07.049
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发表时间：
2007-12-08
影响因子：
5
通讯作者：
Coelho, Marcio M.
中科院分区：
文献类型：
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作者：
Bastos, Leandro Francisco S.;Merlo, Leonardo A.;Coelho, Marcio M.
四环素类药物诱导的抗炎作用与其抗菌活性无关。我们研究了米诺环素和多西环素在伤害性和炎性疼痛、水肿、发热、细胞迁移和纤维血管组织形成模型中诱导的作用，因为这些作用尚未得到充分研究。四环素类药物在试验前1 h通过腹膜内途径给药。米诺环素和多西环素（100 mg/kg）抑制福尔马林诱导的小鼠伤害性反应的第二相。强力霉素（100 mg/kg）也抑制第一相。多西环素（100 mg/kg）可抑制佛波醇12，13-双癸酸酯（PDD）引起的小鼠伤害性反应。此外，多西环素和米诺环素（50或100 mg/kg）抑制角叉菜胶诱导的大鼠机械性异常性疼痛。然而，它们并没有增强热板测试中的潜伏期。抗伤害性感受不太可能由运动不协调或肌肉松弛作用引起，因为两种四环素类药物（100 mg/kg）在旋转杆试验中均未损害小鼠的运动活动。多西环素（50或100 mg/kg）或米诺环素（50或100 mg/kg）抑制角叉菜胶诱导的大鼠足肿胀。然而，只有米诺环素（100 mg/kg）抑制PDD诱导的水肿。两种四环素类药物（100 mg/kg）均可抑制角叉菜胶诱导的大鼠腹腔白细胞迁移。多西环素（50或100 mg/kg）或米诺环素（100 mg/kg）也可抑制内毒素诱导的大鼠发热。最后，两种四环素（50或100 mg/kg/天）给药6天，可抑制小鼠皮下植入棉球诱导的纤维血管组织形成。总之，这项研究清楚地表明了这些第二代四环素类药物的镇痛和抗炎活性。(c)2007 Elsevier B. V.保留所有权利。
Tetracyclines induce anti-inflammatory effects unrelated to their antimicrobial activities. We investigated the effect induced by minocycline and doxycycline in models of nociceptive and inflammatory pain, edema, fever, cell migration and formation of fibrovascular tissue, as these effects have not been fully investigated. Tetracyclines were administered via intraperitoneal route I h before the tests. Minocycline and doxycycline (100 mg/kg) inhibited the second phase of the formalin-induced nociceptive response in mice. Doxycycline (100 mg/kg) also inhibited the first phase. The nociceptive response induced by phorbol 12,13-didecanoate (PDD) in mice was inhibited by doxycycline (100 mg/kg). Furthermore, carrageenan-induced mechanical allodynia in rats was inhibited by doxycycline and minocycline (50 or 100 mg/kg). However, they did not enhance the latency in the hot-plate test. It is unlikely that antinociception resulted from motor incoordination or muscle relaxing effect, as both tetracyclines (100 mg/kg) did not impair the motor activity of mice in the rota-rod test. Doxycyclinc (50 or 100 mg/kg) or minocycline (50 or 100 mg/kg) inhibited carrageenan-induced paw edema in rats. However, only minocycline (100 mg/kg) inhibited PDD-induced edema. Carrageenan-induced leukocyte migration into the peritoneal cavity of rats was inhibited by both tetracyclines (100 mg/kg). Endotoxin-induced fever in rats was also inhibited by doxycycline (50 or 100 mg/kg) or minocycline (100 mg/kg). Finally, formation of fibrovascular tissue induced by subcutaneous implant of a cotton pellet in mice was inhibited by a 6-day administration of both tetracyclines (50 or 100 mg/kg day). Concluding, this study clearly shows the antinociceptive and anti-inflammatory activities of these second-generation tetracyclines. (c) 2007 Elsevier B.V. All rights reserved.