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Updated: Jun 23, 2026
Production and Detection of Reactive Oxygen Species (ROS) in Cancers
Published on: November 21, 2011
Catalase delivery for inhibiting ROS-mediated tissue injury and tumor metastasis
Makiya Nishikawa1, Mitsuru Hashida, Yoshinobu Takakura
1Department of Biopharmaceutics and Drug Metabolism, Kyoto University, Kyoto, Japan. makiya@pharm.kyoto-u.ac.jp
Abstract:
Reactive oxygen species (ROS) have been suggested to be involved in a variety of human diseases. Catalase, an enzyme degrading hydrogen peroxide, can be used as a therapeutic agent for such diseases, but its successful application will depend on the distribution of the enzyme to the sites where ROS are generated. Chemical modification techniques have been used to control the tissue distribution of catalase, and delivery to hepatocytes (galactosylation), liver nonparenchymal cells (mannosylation or succinylation), kidney (cationization) and the blood pool (PEGylation) has been achieved. The effectiveness of catalase delivery has been demonstrated in animal models for hepatic ischemia/reperfusion injury, chemical-induced tissue injuries and tumor metastasis to the liver, lung and peritoneal organs. Significant inhibition was observed in the ROS-mediated oxidative tissue damages and ROS-mediated upregulation of expression of genes responsible for recruitment of inflammatory cells and for metastatic growth of tumor cells. Because oxygen plays a fundamental key role in our life and oxidative stress is implicated in a wide variety of human diseases, catalase delivery could have wide application in the near future.
Insights
This study shows that modifying catalase can deliver it to specific tissues, effectively reducing oxidative stress and tissue damage in animal models. This targeted delivery holds promise for treating various diseases linked to reactive oxygen species.
Area of Science:
- Biomedical Engineering
- Enzymology
- Pathophysiology
Background:
- Reactive oxygen species (ROS) are implicated in numerous human diseases.
- Catalase, an enzyme that degrades hydrogen peroxide, is a potential therapeutic agent.
- Effective therapeutic use of catalase requires targeted delivery to ROS-generating sites.
Purpose of the Study:
- To investigate chemical modification techniques for controlling catalase tissue distribution.
- To evaluate the therapeutic efficacy of targeted catalase delivery in animal models of disease.
Main Methods:
- Chemical modifications including galactosylation, mannosylation, succinylation, cationization, and PEGylation were used to target catalase.
- Delivery efficiency was assessed for hepatocytes, liver nonparenchymal cells, kidney, and the blood pool.
- Efficacy was tested in animal models of hepatic ischemia/reperfusion injury, chemical-induced injuries, and tumor metastasis.
Main Results:
- Targeted delivery of modified catalase to specific tissues was successfully achieved.
- Significant inhibition of ROS-mediated oxidative tissue damage was observed.
- Suppression of gene expression related to inflammation and tumor metastasis was demonstrated.
Conclusions:
- Chemical modification enables targeted delivery of catalase, enhancing its therapeutic potential.
- Targeted catalase delivery effectively mitigates oxidative stress and related pathologies in preclinical models.
- This approach offers a promising strategy for treating a wide range of ROS-associated diseases.
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