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

Abstract

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.

• Authors: Shigeyoshi Honma, Naho Takahashi, Masahiro Shinohara, Kazuki Nakamura, Satoru Mitazaki, Sumiko Abe, Makoto Yoshida
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 715 Issue 1-3 Pg. 181-8 (Sep 05 2013) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 23747596 (Publication Type: Journal Article)
• Copyright: © 2013 Elsevier B.V. All rights reserved.

Chemical References

• Cyclooxygenase 2 Inhibitors
• Thiazines
• Thiazoles
• Thromboxane B2
• Cyclooxygenase 2
• Dinoprostone
• Cisplatin
• Meloxicam

Topics

• Animals
• Cisplatin (adverse effects)
• Cyclooxygenase 2 (genetics, metabolism)
• Cyclooxygenase 2 Inhibitors (pharmacology)
• Dinoprostone (urine)
• Gene Expression Regulation, Enzymologic (drug effects)
• Kidney (drug effects)
• Macrophages (drug effects, immunology)
• Male
• Meloxicam
• Mice
• Mice, Inbred BALB C
• Oxidative Stress (drug effects)
• Thiazines (pharmacology)
• Thiazoles (pharmacology)
• Thromboxane B2 (urine)