Protection by alpha G-rutin, a water-soluble antioxidant flavonoid, against renal damage in mice treated with ferric nitrilotriacetate.
The protective effect of alpha G-Rutin against ferric nitrilotriacetate (Fe-NTA)-induced renal damage was studied in male ICR mice. Fe-NTA induces renal lipid peroxidation, leading to a high incidence of renal cell carcinoma in rodents. Administration of alpha G-Rutin (50 mumol as rutin/kg) by gastric intubation 30 min after i.p. injection of Fe-NTA (7 mg Fe/kg) most effectively suppressed renal lipid peroxidation. Repeated i.p. injection of Fe-NTA (2 mg Fe/kg/day for the first 3 days and 3 mg Fe /kg/day for 12 days, 5 days a week) causes subacute nephrotoxicity as revealed by induction of karyomegalic cells in renal proximal tubules. A protective effect was observed in mice given alpha G-Rutin 30 min after each Fe-NTA treatment. To elucidate the mechanism of protection by alpha G-Rutin, the pharmacokinetics and hydroxyl radical-scavenging effect of alpha G-Rutin were investigated by HPLC analysis and by electron spin resonance (ESR) spin trapping with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), respectively. When mice were given alpha G-Rutin (50 mumol as rutin/kg) by gastric intubation, rapid absorption into the circulation was observed. The plasma concentration of alpha G-Rutin reached the highest level 30 min after oral administration and then decreased to the control level within 60 min, alpha G-Rutin inhibited the formation of DMPO-OH in a concentration-dependent manner. Further, chelating activity of alpha G-Rutin to ferric ions was shown by spectrophotometric analysis. These results suggest that absorbed alpha G-Rutin works as an antioxidant in vivo either by scavenging reactive oxygen species or by chelating ferric ions and this serves to prevent oxidative renal damage in mice treated with Fe-NTA.
Shimoi
K
K
School of Food and Nutritional Sciences, University of Shizuoka.
Shen
B
B
Toyokuni
S
S
Mochizuki
R
R
Furugori
M
M
Kinae
N
N
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D002273:Carcinogens; D002851:Chromatography, High Pressure Liquid; D003497:Cyclic N-Oxides; D004578:Electron Spin Resonance Spectroscopy; D005290:Ferric Compounds / Q000633:toxicity*; D016166:Free Radical Scavengers; D017665:Hydroxyl Radical; D007674:Kidney Diseases / Q000139:chemically induced / Q000517:prevention & control*; D007683:Kidney Tubular Necrosis, Acute / Q000139:chemically induced; D007700:Kinetics; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D015394:Molecular Structure; D009571:Nitrilotriacetic Acid / Q000031:analogs & derivatives* / Q000633:toxicity; D012431:Rutin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013113:Spin Labels; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014312:Trisaccharides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000975:Antioxidants; D002273:Carcinogens; D003497:Cyclic N-Oxides; D005290:Ferric Compounds; D016166:Free Radical Scavengers; D013113:Spin Labels; D017392:Thiobarbituric Acid Reactive Substances; D014312:Trisaccharides; C069037:4(G)-alpha-glucopyranosyl-rutin; D017665:Hydroxyl Radical; D012431:Rutin; C017245:5,5-dimethyl-1-pyrroline-1-oxide; D009571:Nitrilotriacetic Acid; C020326:ferric nitrilotriacetate