Hepatocyte-specific distribution of catalase and its inhibitory effect on hepatic ischemia/reperfusion injury in mice.
To explore the possibility of using catalase for the treatment of reactive oxygen species (ROS)-mediated injuries, the pharmacokinetics of bovine liver catalase (CAT) labeled with 111In was investigated in mice. At a dose of 0.1 mg/kg, more than 70% of 111In-CAT was recovered in the liver within 10 min after intravenous injection. In addition, 111In-CAT was predominantly recovered from the parenchymal cells (PC) in the liver. Increasing the dose retarded the hepatic uptake of 111In-CAT, suggesting saturation of the uptake process. This cell-specific uptake could not be inhibited by coadministration of various compounds which are known to be taken up by liver PC, indicating that the uptake mechanism of CAT by PC is very specific to this compound. The preventive effect of CAT on a hepatic ischemia/reperfusion injury was examined in mice by measuring the GOT and GPT levels in plasma. A bolus injection of CAT at 5 min prior to the reperfusion attenuated the increase in the levels of these indicators in a dose-dependent manner. These results suggest that catalase can be used for various hepatic injuries caused by ROS.
Yabe
Y
Y
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan.
Koyama
Y
Y
Nishikawa
M
M
Takakura
Y
Y
Hashida
M
M
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002352:Carrier Proteins / Q000008:administration & dosage; D002374:Catalase / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D002417:Cattle; D005690:Galactose / Q000008:administration & dosage; D007205:Indium Radioisotopes; D007501:Iron / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000098:blood supply* / Q000201:enzymology*; D008297:Male; D051379:Mice; D015427:Reperfusion Injury / Q000517:prevention & control*; D012710:Serum Albumin, Bovine / Q000008:administration & dosage; D014018:Tissue Distribution; D014503:Urate Oxidase / Q000008:administration & dosage
D002352:Carrier Proteins; D007205:Indium Radioisotopes; C039136:bovine serum albumin-galactose (39); D012710:Serum Albumin, Bovine; D007501:Iron; D002374:Catalase; D014503:Urate Oxidase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005690:Galactose