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Updated: May 10, 2026
Acute Kidney Injury Model Induced by Cisplatin in Adult Zebrafish
Published on: May 15, 2021
Amelioration of cisplatin-induced mouse renal lesions by a cyclooxygenase (COX)-2 selective inhibitor
Shigeyoshi Honma1, Naho Takahashi, Masahiro Shinohara
1Department of Pharmacology, Faculty of Pharmacy, Takasaki University of Health and Welfare, 60 Nakaorui-machi, Gunma 370-0033, Japan. shonma@takasaki-u.ac.jp
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.
Insights
Meloxicam, a cyclooxygenase-2 inhibitor, reduced kidney damage, inflammation, and oxidative stress caused by cisplatin in mice. This suggests meloxicam may protect against cisplatin-induced nephrotoxicity.
Area of Science:
- Nephrology
- Pharmacology
- Toxicology
Background:
- Cisplatin is a widely used chemotherapy agent.
- Cisplatin administration can lead to significant kidney damage (nephrotoxicity).
- Cyclooxygenase-2 (COX-2) plays a role in inflammatory processes and may contribute to cisplatin-induced kidney injury.
Purpose of the Study:
- To investigate the protective effects of meloxicam, a selective COX-2 inhibitor, against cisplatin-induced nephrotoxicity in a mouse model.
- To evaluate the impact of meloxicam on inflammation, oxidative stress, and renal lesions induced by cisplatin.
Main Methods:
- BALB/c mice were administered a single dose of cisplatin (13 mg/kg).
- Mice were simultaneously treated with meloxicam (0.7 mg/kg/day) in drinking water.
- Renal function markers (creatinine, BUN, urinary glucose), COX-2 expression, oxidative stress markers (p47phox, p67phox, HO-1, NOX2, 4-HNE), and inflammatory markers (ERK, JNK phosphorylation, macrophage infiltration) were assessed.
Main Results:
- Cisplatin injection significantly increased renal injury markers, COX-2 expression, oxidative stress markers, and inflammatory signaling pathways.
- Simultaneous treatment with meloxicam attenuated these cisplatin-induced changes.
- Meloxicam inhibited increases in p47phox, HO-1, 4-HNE, ERK, and JNK phosphorylation, and reduced macrophage infiltration.
Conclusions:
- Meloxicam ameliorates cisplatin-induced renal lesions in mice.
- The protective effects of meloxicam may be attributed to the inhibition of inflammatory and oxidative stress responses.
- Targeting COX-2 with meloxicam presents a potential therapeutic strategy to mitigate cisplatin nephrotoxicity.
