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 ag ainst ferric nitrilotriacetate (Fe-NTA)-induced renal lipid peroxidation an d carcinogenesis was studied in male ddY mice. Fe-NTA-induced renal lipid p eroxidation 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 injectio n of Fe-NTA (7 mg Fe/kg) effectively inhibited renal lipid peroxidation. Th is 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 inje ction 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 pleo morphic 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 multil ayered and proliferating large atypical cells. Mice treated with propolis a nd Artepillin C also had cysts, but these were dilated and composed of flat cells. These results suggest that propolis and Artepillin C prevent oxidat ive renal damage and the carcinogenesis induced by Fe-NTA in mice.