Superoxide dismutase (SOD) activity with Fe-chlorin e6-Na and suppression of malignant tumor growth in rats.
Derivatives of porphyrin, specifically Fe-chlorin e6-Na (FeCNa), mimic superoxide dismutase (SOD). This SOD activity was determined by decrease in electron spin resonance (ESR) signals and increase in hydrogen peroxide (H2O2) as the intermediate of O2-. by the coloration using 4-aminoantipyrin. Chlorin e6-Na used for cancer photodynamic therapy (PDT)(1) does not show SOD mimicking activity. The specific activity of FeCNa, comparing with bovine RBC-SOD, was 1/7.5 as determined by ESR analysis. The iron element of Fe-chlorin e6-Na, being tightly encased in the molecule, did not participate in the Fenton reaction. The SOD mimetic activity of FeCNa was stable against physico-chemical treatment such as pH shock, heat and digestion by pronase. For cancer bearing rats with oxidative stress (OS), immediate relief of OS was possible by a single intraperitoneal injection of FeCNa and relief continued for 24 hours. The subsequent administration of FeCNa suppressed cancer growth in vivo.
Kariya
K
K
Department of Biochemistry, Kitasato University School of Medicine, Kanagawa, Japan.
Nakamura
K
K
Nomoto
K
K
Kobayashi
Y
Y
Namiki
M
M
D000818:Animals; D001835:Body Weight; D002735:Chlorophyllides; D004578:Electron Spin Resonance Spectroscopy; D005354:Fibrosarcoma / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D006861:Hydrogen Peroxide / Q000378:metabolism; D007274:Injections, Intraperitoneal; D009374:Neoplasms, Experimental / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010100:Oxygen / Q000378:metabolism; D011166:Porphyrins / Q000627:therapeutic use*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000097:blood* / Q000187:drug effects
D002735:Chlorophyllides; D011166:Porphyrins; D011838:Radiation-Sensitizing Agents; C062985:phytochlorin; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D010100:Oxygen