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

• Published in: European journal of pharmacology Vol. 715; no. 1-3; pp. 181 - 188
• Main Authors: Honma, Shigeyoshi, Takahashi, Naho, Shinohara, Masahiro, Nakamura, Kazuki, Mitazaki, Satoru, Abe, Sumiko, Yoshida, Makoto
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 05.09.2013
• Subjects: Animals; blood; Cisplatin; Cisplatin - adverse effects; COX-2 selective inhibitor; creatinine; Cyclooxygenase 2 - genetics; Cyclooxygenase 2 - metabolism; Cyclooxygenase 2 Inhibitors - pharmacology; Dinoprostone - urine; drinking water; Gene Expression Regulation, Enzymologic - drug effects; glucose; Inflammation; Kidney - drug effects; macrophages; Macrophages - drug effects; Macrophages - immunology; Male; meloxicam; messenger RNA; Mice; Mice, Inbred BALB C; mitogen-activated protein kinase; NADP (coenzyme); Oxidative stress; Oxidative Stress - drug effects; phosphorylation; prostaglandin synthase; Renal lesions; stress response; Thiazines - pharmacology; Thiazoles - pharmacology; Thromboxane B2 - urine; urea nitrogen; COX-2 selective inhibitor; Renal lesions; Oxidative stress; Inflammation; Cisplatin
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2013.05.023

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 (13mg/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 (0.7mg/kg/day in drinking water). The expression of oxidative stress markers, p47phox, p67phox, 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 p47phox, 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.