title: 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.affiliation: Department of Pharmacology, Faculty of Pharmacy, Takasaki University of Health and Welfare, 60 Nakaorui-machi, Gunma 370-0033, Japan. shonma@takasaki-u.ac.jp
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Honma
authors.forename: Naho
authors.initials: N
authors.lastname: Takahashi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Shinohara
authors.forename: Kazuki
authors.initials: K
authors.lastname: Nakamura
authors.forename: Satoru
authors.initials: S
authors.lastname: Mitazaki
authors.forename: Sumiko
authors.initials: S
authors.lastname: Abe
authors.forename: Makoto
authors.initials: M
authors.lastname: Yoshida
mesh_terms: D000818:Animals; D002945:Cisplatin / Q000009:adverse effects*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000652:urine; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007668:Kidney / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D000077239:Meloxicam; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress / Q000187:drug effects; D013843:Thiazines / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000652:urine
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D013843:Thiazines; D013844:Thiazoles; D013929:Thromboxane B2; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D002945:Cisplatin; D000077239:Meloxicam
keywords: COX-2 selective inhibitor; Cisplatin; Inflammation; Oxidative stress; Renal lesions