Renal carcinogenesis induced by ferric nitrilotriacetate in mice, and protection from it by Brazilian propolis and artepillin C.
The protective effect of Brazilian propolis and its extract Artepillin C against ferric nitrilotriacetate (Fe-NTA)-induced renal lipid peroxidation and carcinogenesis was studied in male ddY mice. Fe-NTA-induced renal lipid peroxidation leads to a high incidence of renal cell carcinoma (RCC) in mice. Administration of propolis by gastric intubation 2 h before or Artepillin C at either the same time, 2 h, or 5 h before the intraperitoneal injection of Fe-NTA (7 mg Fe/kg) effectively inhibited renal lipid peroxidation. This was evaluated from the measurement of renal thiobarbituric acid-reactive substances (TBARS) or histochemical findings of 4-hydroxy-2-nonenal (4-HNE)-modified proteins and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Repeated injection of Fe-NTA (10 mg Fe/kg per day, twice a week for a total of 16 times in 8 weeks) caused subacute nephrotoxicity as revealed by necrosis and pleomorphic large nuclear cells in the renal proximal tubules, and gave rise to RCC 12 months later. A protective effect from carcinogenicity was observed in mice given propolis or Artepillin C. Furthermore, the mice given Fe-NTA only developed multiple cysts composed of precancerous lesions with multilayered and proliferating large atypical cells. Mice treated with propolis and Artepillin C also had cysts, but these were dilated and composed of flat cells. These results suggest that propolis and Artepillin C prevent oxidative renal damage and the carcinogenesis induced by Fe-NTA in mice.
Kimoto
T
T
Hayashibara Biochemical Laboratories Inc., Fujisaki Institute, Fujisaki, Okayama, Japan.
Koya
S
S
Hino
K
K
Yamamoto
Y
Y
Nomura
Y
Y
Micallef
M J
MJ
Hanaya
T
T
Arai
S
S
Ikeda
M
M
Kurimoto
M
M
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000139:chemically induced / Q000188:drug therapy* / Q000517:prevention & control; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D004195:Disease Models, Animal; D004578:Electron Spin Resonance Spectroscopy; D005260:Female; D005290:Ferric Compounds / Q000633:toxicity; D019084:Fluorescent Antibody Technique, Indirect; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007680:Kidney Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000517:prevention & control; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D009153:Mutagens / Q000633:toxicity; D009571:Nitrilotriacetic Acid / Q000031:analogs & derivatives* / Q000633:toxicity; D010666:Phenylpropionates / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011429:Propolis / Q000008:administration & dosage / Q000627:therapeutic use*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000447:Aldehydes; D000970:Antineoplastic Agents; D005290:Ferric Compounds; D009153:Mutagens; D010666:Phenylpropionates; D017392:Thiobarbituric Acid Reactive Substances; C102259:artepillin C; D000080242:8-Hydroxy-2'-Deoxyguanosine; D011429:Propolis; D003849:Deoxyguanosine; C027576:4-hydroxy-2-nonenal; D009571:Nitrilotriacetic Acid; C020326:ferric nitrilotriacetate