کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5830661 | 1559121 | 2008 | 6 صفحه PDF | دانلود رایگان |
Effects of docetaxel, a taxane-derivative anti-cancer drug, on lipopolysaccharide (LPS)-induced nitric oxide (NO) synthesis were investigated in alveolar macrophages isolated from rats. LPS-induced NO production and inducible NO synthase (iNOS) expression were significantly enhanced in the macrophages isolated from rats injected intraperitoneally with docetaxel (4 mg/kg body weight per day for 5 consecutive days) compared with those in macrophages from control rats administrated a vehicle. In vivo administration of docetaxel augmented LPS-induced p38 activation but not extracellular signal-related kinase (ERK) activation in isolated macrophages. On the other hand, in vitro treatment of macrophages with docetaxel (5 and 10 μg/ml) inhibited LPS-induced NO production and iNOS expression. Levels of lactate dehydrogenase released from macrophages were neither affected by in vitro treatment with docetaxel (up to 10 μg/ml) nor by its in vivo administration. These results suggest that docetaxel has an enhancing action in vivo on LPS-induced iNOS expression and subsequent NO production through stimulation of p38 activity in alveolar macrophages.
Journal: European Journal of Pharmacology - Volume 580, Issue 3, 12 February 2008, Pages 425-430