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. 1997 May;88(5):453–460. doi: 10.1111/j.1349-7006.1997.tb00403.x

Protection by αG‐Rutin, a Water‐soluble Antioxidant Flavonoid, against Renal Damage in Mice Treated with Ferric Nitrilotriacetate

Kayoko Shimoi 1,✉, Bingrong Shen 1, Shinya Toyokuni 2, Rika Mochizuki 1, Michiyo Furugori 1, Naohide Kinae 1
PMCID: PMC5921458  PMID: 9247601

Abstract

The protective effect of aG‐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 αG‐Rutin (50 μmol as rut in/leg) 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 FeAg/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 αG‐Rutin 30 min after each Fe‐NTA treatment. To elucidate the mechanism of protection by αG‐Rutin, the pharmacokinetics and hydroxyl radical‐scavenging effect of αG‐Rutin were investigated by HPLC analysis and by electron spin resonance (ESR) spin trapping with 5,5‐dimethyl‐l‐pyrroline‐N‐oxide (DMPO), respectively. When mice were given αG‐Rutin (50 μmol as rutin Ag) by gastric intubation, rapid absorption into the circulation was observed. The plasma concentration of äG‐Rutin reached the highest level 30 min after oral administration and then decreased to the control level within 60 min. äG‐Rutin inhibited the formation of DMPO‐OH in a concentration‐dependent manner. Further, chelating activity of äG‐Rutin to ferric ions was shown by spectrophotometric analysis. These results suggest that absorbed äG‐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.

Keywords: Flavonoid, Antioxidant, αG‐Rutin, Ferric nitrilotriacetate, Renal damage

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