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Acute Kidney Injury Model Induced by Cisplatin in Adult Zebrafish
Published on: May 15, 2021
Combining cisplatin with cationized catalase decreases nephrotoxicity while improving antitumor activity
S-F Ma1, M Nishikawa, K Hyoudou
1Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.
Kidney International
|September 28, 2007
Summary
Cationized catalase protects against cisplatin-induced kidney damage in mice, improving chemotherapy survival without affecting tumor reduction. This catalase derivative offers a promising strategy to mitigate chemotherapy side effects.
Area of Science:
- Biochemistry
- Pharmacology
- Nephrology
Background:
- Cisplatin is a vital chemotherapy drug for solid tumors.
- Nephrotoxicity is a major dose-limiting side effect of cisplatin, mediated by reactive oxygen species.
- Developing strategies to mitigate cisplatin-induced kidney damage is crucial for effective cancer treatment.
Purpose of the Study:
- To evaluate the protective effect of cationized catalase against cisplatin-induced nephrotoxicity in a mouse model.
- To compare the kidney accumulation of cationized catalase with native catalase.
- To assess the impact of cationized catalase on cisplatin's efficacy against tumor growth and overall survival.
Main Methods:
- Immunohistochemistry was used to assess catalase distribution in the kidneys.
- Mice were treated with cisplatin and varying doses of cationized catalase.
- Renal function markers (serum creatinine, BUN), oxidative stress markers (MDA, glutathione), and kidney histology were analyzed.
- Tumor growth and survival rates were monitored.
Main Results:
- Cationized catalase demonstrated enhanced accumulation in the kidneys compared to native catalase.
- Cationized catalase significantly reduced cisplatin-induced elevations in serum creatinine, BUN, nitrite/nitrate, and LDH.
- It also attenuated cisplatin-induced decreases in renal glutathione and increases in malondialdehyde.
- Cationized catalase blunted proximal tubule necrosis but did not affect tumor growth inhibition by cisplatin.
- Survival rates were significantly improved in cisplatin-treated mice receiving cationized catalase.
Conclusions:
- Cationized catalase effectively mitigates cisplatin-induced nephrotoxicity in mice.
- This protective effect enhances the therapeutic index of cisplatin by preventing acute toxicity and improving survival.
- Catalase derivatives represent a potential adjuvant therapy to improve the clinical application of cisplatin for solid tumors.
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