Catalase delivery for inhibiting ROS-mediated tissue injury and tumor metastasis.
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.
Nishikawa
Makiya
M
Department of Biopharmaceutics and Drug Metabolism, Kyoto University, Kyoto, Japan. makiya@pharm.kyoto-u.ac.jp
Hashida
Mitsuru
M
Takakura
Yoshinobu
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002374:Catalase / Q000008:administration & dosage*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D009362:Neoplasm Metastasis / Q000188:drug therapy / Q000473:pathology*; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity*
D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D002374:Catalase