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1.
Artigo em Inglês | IMSEAR | ID: sea-37536

RESUMO

Studies were undertaken to determine whether bovine lactoferrin (bLF) and related compounds, shown to prevent carcinogenesis in the colon and other organs in rats, have any toxic effects in long-term feeding studies. In experiment I, male F344/DuCrj rats received a basal diet containing 0.2% bLF for 40 weeks. No adverse findings were noted, furthermore, serum triglyceride level was significantly decreased to 72% of the control level, suggesting preventive effects against the metabolic syndrome. In experiment II, male and female F344/DuCrj rats were fed a basal diet containing 0.02, 0.2, 2.0 and 5.0% bLF, 2.0% bLF hydrolysate (bLF-H) or 0.1% lactoferricin (LFcin), a peptide derived from bLF, for 60 weeks in males and 65 weeks in females. No toxicological effects, including carcinogenicity, were evident in either sex. The results of the studies provide subjective support for safety of clinical studies of bLF for supplement use.


Assuntos
Ração Animal , Animais , Bovinos , Doença Crônica , Feminino , Lactoferrina/toxicidade , Masculino , Neoplasias Experimentais/induzido quimicamente , Nível de Efeito Adverso não Observado , Ratos , Ratos Endogâmicos F344 , Triglicerídeos/sangue
2.
Artigo em Inglês | IMSEAR | ID: sea-37829

RESUMO

Phenobarbital (PB), a rodent non-genotoxic carcinogen, showed hormesis, biphasic effects on rat liver carcinogenesis. To test the hypothesis that the hormesis earlier observed for PB induced hepatocarcinogenesis might also exist in the TGF-alpha transgenic mice model, one which is highly susceptible to carcinogenesis, the carcinogenic or promotion effects of a wide range of phenobarbital (PB) concentrations were investigated. Two weeks after a single i.p. dose of 5 mg /kg bw of diethylnitrosamine (DEN) to 15 day old mice, animals were treated with diet containing PB at doses of 0, 2, 15 or 500 ppm. The incidence and multiplicity of tumors, including hepatocellular adenomas and carcinomas, were significantly increased by the high dose of PB, but no significant difference among the groups receiving 2 and 15 ppm for liver tumors when compared to DEN alone group. The proliferating cell nuclear antigen indices for liver tumors and surrounding hepatocytes in high dose PB treated mice were significantly increased, but no change was noted at the lower doses. The total cytochrome P450 content in the liver was also elevated by 500 ppm of PB, while hepatic 8-OHdG levels demonstrated no significant change. In conclusion, PB at high dose enhances DEN-induced hepatocarcinogenesis in TGF-alpha transgenic mice, but low doses lack any significant effects. One possible mechanism of phenobarbital carcinogenicity might be influenced by cytochrome P450 system exhibiting a strong promoting activity for liver of mice.


Assuntos
Animais , Anticonvulsivantes/administração & dosagem , Testes de Carcinogenicidade , Carcinógenos/administração & dosagem , Dietilnitrosamina/administração & dosagem , Relação Dose-Resposta a Droga , Neoplasias Hepáticas/induzido quimicamente , Camundongos , Camundongos Transgênicos , Fenobarbital/administração & dosagem , Fator de Crescimento Transformador alfa/genética
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