Amelioration of cisplatin-induced mouse renal lesions by a cyclooxygenase (COX)-2 selective inhibitor

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• 作者：Shigeyoshi Honma ; Naho Takahashi ; Masahiro Shinohara ; Kazuki Nakamura ; Satoru Mitazaki ; Sumiko Abe ; Makoto Yoshida
• 关键词：Cisplatin ; COX-2 selective inhibitor ; Renal lesions ; Oxidative stress ; Inflammation
• 刊名：European Journal of Pharmacology
• 出版年：2013
• 出版时间：5 September, 2013
• 年：2013
• 卷：715
• 期：1-3
• 页码：181-188
• 全文大小：1779 K

文摘

In this study, we investigated the effects of the cyclooxygenase (COX)-2 selective inhibitor, meloxicam, on cisplatin-induced inflammation, oxidative stress and renal lesions in BALB/c mice. A single cisplatin injection (13 mg/kg, i.p.) significantly increased plasma creatinine, blood urea nitrogen and urinary glucose accompanied by a concomitant increase in COX-2 mRNA and COX-2 protein levels. These changes in renal lesion parameters were diminished by simultaneous treatment of meloxicam (0.7 mg/kg/day in drinking water). The expression of oxidative stress markers, p47^phox, p67^phox, hemoxygenase-1 (HO-1), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) and 4-hydroxy-2-nonenal (4-HNE)-modified protein were increased with cisplatin injection. Simultaneous treatment of meloxicam with cisplatin significantly inhibited the increase in p47^phox_, HO-1 and 4-HNE-modified protein. The phosphorylation of extracellular regulated kinase (ERK) and c-jun-N-terminal kinase (JNK) were increased with cisplatin injection, but these changes were inhibited by meloxicam. Moreover, concomitant meloxicam treatment also prevented the cisplatin-induced infiltration of macrophages to the tubulointerstitial area. These results suggest that meloxicam can ameliorate cisplatin-induced mouse renal lesions, potentially through the inhibition of inflammatory and oxidative stress responses.