RESUMO
The anticarcinogenic effect of garlic has been demonstrated in both epidemiologic and experimental studies. In this study, possible mechanisms involved in the anticarcinogenic effect of garlic consumption were assessed by determining its capacity to alter drug metabolizing enzymes, in relation with its alliin content. Rats were fed a diet for 2 weeks containing 5% garlic powders produced from bulbs grown on soils with different levels of sulfate fertilization and therefore containing differing amounts of alliin. Activities of several hepatic enzymes, which are important in carcinogen metabolism such cytochromes P450 (CYP) and phase II enzymes, were determined. Garlic consumption slightly increased ethoxyresorufin O-deethylase and CYP 1A2 levels. In contrast, garlic consumption decreased CYP 2E1 activity and the level of the corresponding isoform. UDP glucuronosyl transferase and glutathion S-transferase activities were increased by garlic powders. The alliin content of the garlic powders was positively correlated with UGT activity although not with other activities. Effects produced by garlic consumption were qualitatively similar to that of diallyl disulfide, a sulfur compound that has been extensively studied. These data could partially explain the chemoprotective effect of garlic.
Assuntos
Cisteína/análogos & derivados , Cisteína/análise , Dieta , Alho/química , Fígado/enzimologia , Animais , Anticarcinógenos , Cisteína/farmacologia , Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP1A2/metabolismo , Citocromo P-450 CYP2E1/metabolismo , Glucuronosiltransferase/metabolismo , Glutationa Transferase/metabolismo , Masculino , Ratos , Ratos WistarRESUMO
Garlic (Allium sativum) is well known for its beneficial effects on health and particularly for its chemopreventive potential against cancer. The present study was designed to compare the chemopreventive efficacies of several garlic powders with various levels of alliin, a precursor of active sulfur compounds. For this purpose we used the medium-term hepatocarcinogenesis protocol (resistant hepatocyte model), which allows the detection of preneoplasic foci expressing the placental form of glutathione S-transferase (GST-P) as an end-point. Rats were fed diets containing three garlic powders (5% of the diet) with various alliin contents for 3 weeks. Garlic powders were obtained from bulbs grown on soils with different levels of sulfur fertilization. During the period of garlic feeding hepatocarcinogenesis was initiated by administration of 10 i.p. injections of 0.025 mg/kg body weight aflatoxin B1 (AFB1). The rats were later submitted to 2-acetylaminofluorene treatment and partial hepatectomy, and GST-P foci were detected and quantified. Consumption of diets containing garlic powders decreased the appearance and size of hepatic GST-P foci. A strong reduction was observed in rats fed garlic containing the highest level of alliin. In addition, increased alliin content of the garlic powder was associated with a proportional decrease in the number and area of preneoplastic foci. Elsewhere, garlic powder ingestion increased hepatic ethoxyresorufin deethylase, glutathione S-transferase and UDP glucuronosyl transferase activities while no modification of nifedipine oxidase activity was found. We also observed an increase in the levels of GST A5 and AFB1 aldehyde reductase. It is suggested that garlic partly exerts its anticarcinogenic effects through increasing enzymes involved in AFB1 detoxification. This study highlights the possibility of controlling the cultivation conditions to improve the chemopreventive efficacy of garlic.